BISBENZYLIS0QT;INOLINE ALKALOIDS--A REVIEW

K. P. GUHA and B. MCKHERJEE Depar tmen t of Piiarmacologg, B . C. R o y P o s t Graduate Ins t i t u t e of Bas i c J fed ica l Sc iences ,

244B, d c i i a r y a J . C . Bose Road , Calcutta-700 020, Ind ia and

R . MUKHERJEE Fiicitldade de Farmacia , L-ni;.ersidade Federal d o Rio Grande d o Sztl,

Porio .4legre, RS, Brasi l

.$BSTR.xT.-The review presents a glossary of the bisbenzylisoquinoline a k a - loids. The following information is tahulated: structural formulas of all the bis- benzj-lisoquinoline alkaloids (BBI) with their molecular formulas: molecular n-eights: mp and : a ] ~ values: uv, ord, nnir, mass data: degradation methods applied to de- termine their striictures: and sourres. -i list of the plants n-ith the particular part studied and the BBI alkaloidis) isolated from each source is furnished. In addition, this article summarizes the distribution of different t>-pes of BBI alkaloids in dif- ferenf genera, methods of isolation, and degradative techniques applied for structure elucidation.

Since the days of the earliest commercial drug preparations, viz., R a d i i pareira bratae, Bebeerii im pirrum and Curare (the arron- poison of South A%merican Indians), natural products chemists and pharmacognosists have been interested in the bis- benzylisoquinoline (BBI) alkaloid- because of their diverse formulations and varied pharniacological effects. Several reviews on the BBIs are already available (1-Sa). The article by Shamma ( 7 ) covers different chenlical aspects of thi. field and has intensified the long-felt need for a glossary of these alkaloids containing all information nece.sarj- for a natural product chemist searching for nen- BBI alkaloid-.

BBI alkaloids are built up of tn-o benzylisoquinoline (BI) units linked by ether bridges. In addition to this ether linkage. methr lenosy bridging or direct carbon carbon bonding is also found between the two BI units. A variety of structural patterns arise in the BBI molecules due to differences in (1.) the number of aromatic oxygen subqtituent- present ; (2.) the number of ether linkage>; (3.) the nature of ether bridges, viz., diphen! 1 ether or benzylphenyl ether: and (4.) the sites on the tn-o BI unit- at n hich the ether or the carbon carbon bond originates. Based on these differences. the BBI alkaloids are claqsified into the groups and subgroups as shon n in table 1.

Individual members in each group differ simplJ- in (1.) the nature of the osyge- nated substituents (OH, OMe, OCH,O) : (2.) the nature of substitution of the t n o nitrogen atonis ISH. S l l e , S - l I e r3 S O ) ; (3.) the degree of unsaturation of the hetero ring.: and (4.) the stereochemistrj- of the tu-o asymmetric centers.

BOTAA ICAL bocmE.-DiW-ibution of the different groups of BBI alkaloids in different genera and the botanical sources of these alkaloids are depicted in tables 2 and 3 respectively.

Ecological factors affect the nature and amount of BBI alkaloids in plants. Cissampelos pareira Linn. from Kashmir yielded h a p t i n e (So. 1 3 i , table 4) and hayatinine (So. 138. table 4) (both S S I type); xhereas a plant from Pilibhit yielded hayatine and curine ( S o . 133, table 4) (=.anie type), but no hayatinine (10); the plants from lladra. and Madagascar contained, in addition to hayatine and curine, isocliondodendrine ( S o . 122. table 4) (S type), which was not found in the extracts from Pilibhit and Kashmir (1 1).

The present report ainis to fulfill this demand.

2 J o c R s a L O F ~ A T ~ R A L PRODUCTS [VOL. 42, so. 1

TABLE 1. Structural classzficafioii of the bzsbene3'1isopuinoline alkalozds.

The numbering system is shon-n in expression I . The rings C and C' are always numbered so as to assign the smallest numbers to the substituents on these rings. The Shamma-Moniot nomenclature for the BBI's has been followed (9) .I However, for purposes of simplification, the different types have also been designated by simple Roman numerals as indicated below.

A. OSE DIPHEiYYL ETHER LIXKAGE.

a. Tail t o tail

6,7,11* ,12-G,i,12* I G,7,11*,12-5,6,7,12* Ia

6,7,10*,12,13-6,7,12* I1 5,G,i,11*,12-5,6,7,12* 111

b. Head to head c . Head to tail A

R2- R; R I

G,i,8*,12-6,7*,12(11-11) IV G,i,11*,12-6,7*,12 V

B. TKO DIPHENYL ETHER LINKAGES.

a. Head to head and tail to tail

G , i * ,11 t , 1 2 4 , i ,8*, 12 t VI

B o d 5,G,7,8*,12j-S,i*,llt,12 VI1

JAS-FEB 19 i9 ] GUHA ET -4~. : BISBESZTLISOQUISOLISE ALKALOIDS 3

6,7,S*,llt,l2-G,i*,12t \I11

0 - R G

c,i,8*,lltJl2,l3-G,7*,12t X

b. Only head to head

tLqg 6,i",8i,12-6*,it,12(11-11~ S V I I I

5,GJ7,S*,lli,l2-G,7*,12t IX

G,7, S* , 1 1 t , 12-G* , 7,12t XI

5*,6,i,11t,12-5,G,iJS*,12t XI11

5,6,7,8*,10~,11,12-6,i*,12~ XV11

JOURXAL OF NATURAL PRODUCTS [VOL. 42, NO. 1 4

c. Head to tail

''l-;%&{ \ / H- R;

' 0-n5Rkr0 ' G,7,8*,12t-G,7,8tJ12* XX G, 7,8* , 11 t ,12-6,7t, 12* XX I

c. OSE DIPHESTL ETHER . iXD O X E BESZTL PHENYL ETHER LIN1i.IGES.

G,iJ8*,12*-G,7,8*[7-12] XXII

D. THREE DIPHESYL ETHER LISKAGES.

E. T W O DIPHESYL ETHER . I S D ONE PHENYL-BENZYL ETHER LINKAGES.

Rl-N C H i Rl

G,7,8*,llt,12,13-6,7*,12t[8-6] XXV G,7,8*, 12 t-6,7,8t, 12* [ 11-71 XXVI

'The tm-o sets of numbers denoting the oxygenated sites are separated by a hyphen. The more highly oxygenated benzylisoquinoline half constitutes the left hand side of the dimer, and is listed first. I n the case of head to tail coupling, the more highly oxygenated benzylisoqui- noline is placed on top. and is listed first. An asterisk (*) or other symbol (t or i) on the upper right of a number indicates the terminal of a diary1 ether. Numbers between paren- theses, appearing directly after the listing of oxygenated sites, describe the positions of a biphenyl linkage.

From samples of Dapkizaizdra micraittha Benth., collected from Sev- South Wales, Bick (12) separated micranthine (So . 159, table 4) (XXIII type) as the minor constituent, the major alkaloids being daphnandrine and daphnoline (Kos. 37 and 38. respectively, table 4) (both VI type). I n specimens from Southern Queensland, Bick isolated mainly micranthine with little or none of the other

J A N - F E B 19791 GUH.4 ET AL. : B I S B E N Z Y L I S O Q U I K O L I X E ALKALOIDS 5

two alkaloids. I n samples collected from the Whian State Forest, Australia, 0-methyl- and LY,O-dimethylmicranthine (Sos. 158, 156, respectively, table 4) accompanied micranthine, but no trace of daphnandrine or daphnoline (13) could be found.

Indian Mahonia plants have been found in many instances to contain both oxyacanthine ( S o . 48) (VI type) and berbamine (So. 57) (VI11 type): nhereas the Japanese Mahonias yield isotetrandrine (So. 62) and berbamine, both of type VI11 (14). Only one Japanese Mahonia, M . for tu i ie i (Hort.) Fedde, was found to contain oxyacanthine (15).

Stephaiz ia ro tunda Lour. from the Caucasus gave cycleanine (KO. 121) (16) but the plants from India did not. Leaves of Magnolia f u s c a t a Andr. collected from Russia gave both magnoline ( S o . 12) (I type) and magnolamine (So . 15) (I1 type), Tvhile those from Japan gave magnolamine only (17).

Moreover. the alkaloids vary in nature and in relative proportion in different parts of the plant. Leaves of M e i i i s p e r m u m catiadeiise Linn. contain no alkaloid; whereac, other parts of the plant--stem. root, and rhizome-contain alkaloidq of type I (18). Similarly, in the case of Mahori ia for tu i ie i Fedde, the trunk is found to contain berbamine (So . 57) and oxyacanthine ( S o . 48) (15) although its leaves do not contain any BBI alkaloid (19).

ISOLATIOX OF aLE;iLoIDs.-The iqolation of BBI alkaloids is, itself, a challenge for the natural products chemiqt. -1 survey of general methods of iqolation i p

therefore prebented. The plant material, leaf. stem, bark, root or rhizome, iq rarely defatted (13s).

I t is generally extracted b j percolation at room temperature u-ith methanol or ethanol [isopropyl alcohol has alqo been used ( i 9 ) ] or 1-570 acidic alcohol. The acid ib normally acetic acid; Barton (12s) used 27, niethanolic tartaric acid solu- tion. Use of other solvents for this extraction was albo reported, e.g., petroleum ether (i6. 58), benzene (1%) and dichloroethane (1'7). Impregnation of the plant with ammonium hydroxide prior to extraction is also known (11, 17, 164); the bark of Daphnaizdra micraiitlza m s extracted with methanol-chloroform-ammonia (15 :5:1) (13). Ihpchan (58) used 1.5% triethylamine in methanol. and Cava (21) used aqueous ammonia-ether for the extraction of Cissampe los pare ira and -4 bufa grisebachii , respectively.

Removal of solvent in vacuum results in a gummy macs n hich is treated with 1 to 57, aqueous solution of acetic, citric, tartaric, hydrochloric or sulfuric acid. Only Cava (54) used phosphoric acid solution, and von Bruchhauqen used boiling 1% hydrochloric acid (11i). Hon-ever, reports of the extraction of alkaloids directly from the plant by aqueous acid solution are also known (12, 25, 49, 10'7).

To remove the non-alkaloidal matters from the aqueous acid extracts, Icing (25) and Toniita (14, 15) precipitated them with lead acetate; the excess lead was then removed as lead sulfide. Xow the general method is to remove them by treatment with light petroleum ether or ether. Ihpchan ( i 9 ) has also used hep- tane and toluene. I n several cases (lo), the pH of the solution is adjusted to 5 with the addition of sodium bicarbonate to precipitate non basic material. Cava (54) extracted the alkaloids from the alcoholic extracts using ammoniacal ethyl acetate. After the removal of the solvent, the gummy mass was treated n-ith 2 7 , aqueous sulfuric acid to separate the baiic wbqtances.

The aqueous acid extracts are then basified n-ith alkali colution to pH 8-9. The total alkaloid fraction precipitates.

The number of alkaloids in the crude alkaloidal mixture is assessed by paper or thin-layer chromatography. Attempts to resolve the BBI alkaloids by paper

Hot alcohol extraction x a s done by Boissier (11).

6 JOURNAL OF K - 4 T U R A L P R O D U C T S [VOL. 42, NO. 1 TABLE 2. Distr ibut ion of tile different groups of bisbenzylisoquinoline aLka!oids in different genera.

Family

Aristolochiaceae Anonaceae.. . .

Berberidaceae

Buxaceae Hernandiaceae Lauraceae

Magnoliaceae Menispermaceae

Monimisceae

h-ymphaceae Ranunculaceae

Rbtlmnaceae Umbelllierae

Genus

Ariatolochia Cremastospermu Guatteria Isolona P haean thus Uvaria Berberis Mnhonia Buxus Gyrocarpus Lindera Neet andra Magnolia Abuta Anisocyclea Anomospermum Chondodendron Cissampeloa Cocculus Cyelea Epinetrum Limacia Menispermum Pachygone Paracyclea Pleogyne Pycndrrhena Scisdotenia Stephania Tiliacora Tricliaia At herorperma Daphnandra Dryndodaphne Laurelia Nemuarnn Nelumbo Thalictrum Xanthorhiza Colubrina Heracleum

~ -

s o . of ,peciee tudiec

1 1 1 1 1 1

21 13

1 1 1 1 2 4 1 1 5 4 6 5 3 2 2 1 1 1 3 1 8 4 3 1 8 1 1 1 li 1

1 2 1

I

-

3

1

1 2

1 5

2

1

No. of BBI alkaloids obtained

IV

1

5

3

VI

3 1

2 1 4 2

3 2

1

1

fi

2

5

G 1 1

-

v111

1

3 2

2

1

4

2 13

1

fi

6 3 5 3 1

1

4 1 1

-

chromatography were first made by Tomita and Watanabe (177) using paper pre- treated with buffer of pH 3.5 and the solvent system n-butanol-acetic acid-water (67:10:23 v/v). Chan (106) impregnated Whatman paper S o s . 1 and 4 with 0.2M potassium hydrogen orthophosphate prior to descending paper chromato- graphy and identified eight spots in the crude alkaloid mixture of Ocotea rodiaei by using the solvents (1 .) 12-butanol-glacial acetic acid-water (G3:10:27) and ( 2 . ) benzene-glacial acetic acid-water (G:7 :3). Kidd ( l i s ) used the upper layer of the solvent mixture: amyl alcohol (110 nil), pyridine (110 ml), and mater suficient for saturation (approximately 90 ml). For the detection of the non-phenolic alkaloids, Dragendorff’s reagent n-as used. With phenolic alkaloids, the red spots obtained

J r l S - F E B 19'791 GUHA E T AL. : B I S B E K Z Y L I S O Q U I S O L I S E ALKALOIDS 7

TABLE 2. Dis tr ibut ion oj' the dif ferent ~ r o u p s oj' bisben~Tl i soquinol ine alkaloids in dif ferent genera.

S o . of BBI alkaloids obtained

1

XV I

-- X I " ~ xV

YVIII XIX YXlI YVI I 1 mined

-

1

1

2 1

!

1

1

1

1 8 5

3

1 1

1 1

1

3 2

3 3

2 1

2 2

1

!

2

1

2

2

3

2

, 3

6

2

1

2 2

with this reagent were too transient ; Folin-Denis reagent followed by alcoholic ammonia was found to be more satisfactory. Bick (1i9) was able to separate a few type VI alkaloids on Whatman paper S o . 1 using a solvent mixture of butanol- acetic acid-water of varying proportions. The spots were detected by spraying the dried paper first n-ith the potassium salt of tetrabromophenolphthalein ethyl ester (@.IT) and then TT-itli an aqueous solution (0.05%) of oxalic acid.

Thin layer chromatography i- more ividely used to aqcay the alkaloidal mix- ture, Dopke (150) employed silica gel plates prepared n i th 0.1 S Sodium hy- droxide to ceparate the compound< of greater ba.icity. phaeanthine. i-otetrandrine, pycnamine. berbamine and oxyacanthine. Bo i4e r ( 1 i 3 ) u-ed this method for

8 JOURNAL OF NATURAL PRODUCTS [VOL. 42, NO. 1

TABLE 3. Botanical sources of bisbenzylisoqiLinoline alkaloids. (Serial No., according to Table 4, of the alkaloid is placed by the side of its name).

S a m e of the plant

Abufa cnndicans Rich ex nC.. . . . . . . . . .

4 . grisebachii Triana and Planchon (Chondodendron candisans Sandaitli)

4 . panurensis Eichl.. . . . . . .

A . splendida Krukoff and Moldenke

.-inisoc>clea gradidini H. Bn.. . . . . . .

d ~ o m o s p e r m i r m prandifolium Eichl. . . Aristolochia Indica Linn. . . . . . . . . . . . . dtherosperma moschatum Labill.. . . . . . .

A . repanddum F. Muell.. . . . . . . . Berberis amicrensis Rupr.. . . . . . .

B. aquifolium Pursch. . . . . . .

B. drislata DC.. . . . . . . . . . . . . . . . B. asiatica Rosb. ex DC.. . . . B. ,floribunda \Tall. ex Don.

B..fortunei Lindl.. . . . . . . B. heteropoda Schrenk B. himalaica Ahrendt . . . . B. inlegerrima . . . . . . . . . . . . . . . . . . . .

B. japonica R. Br. . . . . . . . . . . . . Berberis julianae Schneid. . . . . . .

B. kawakamii Hayata

B. lambertii R. S. Parker

B. laurina (Thunb.) Billb.. . . . . . . . . . .

. . . . . . . . B. (aristafa)

B. lycium Royle . . . . . . . . . B. mingelsensis Hayata . . . . . . . . . . . . . . . . .

B. morrisonemis Hayata . . . . . . . .

B. oblongn. . . . . . . . . . . . . . . . . .

Plant part studied

Stem

Stem

Stem

Stem

Stem

Stem Root Leaf Bark

See Daphiiavdri Stem

Root

See Berberi. Root, bark stem Root

See .Ifahonti See Berber!

Stem-bark Leaf

See Jfahonzr Root

Root

Root

Root-bark

Trunk-bark and root

Root

Root and stem

Alkaloid

(+)-Curine 132 (20) !-)-Isochondodendrine 122 120) Grisabine 10 (21) Magnoline 12 (21) i-0-Demethylpeinamine 60a (?la) JIacolidine 44a (21a) Jlacoline 44b (21a) A-Methyl ,i-0-demethylpeinamine

Peinamine i l a (21a) Norpanurensine 109 (22) Panurensine 110 122) Aromoline 31 123) Homoaromoline 42 (23) Rrukovine 63 (23) 12'-0-Demethyltrilobine 155 (24) (-)-Epistephanine 41 (24) Stebisimine 51 (24) Trilobine 163 (24) (+)-Tubocurarine 142 (25 ) (-)-Curine 133 (26) Atherospermoline 56 (27) Berbamine 5 i (28) Isotetrandrine 6 2 (28) ?pai?diclum F. Muell. Berbamine 5i (29) Berbamunine 1 (29) Berbamine 5 i (30) Oxyacanthine 48 (30) oribmda Wall. ex Don. Berbamine 5i (31) Berbamine 57 (32) 0x3-acanthine 48 (32) irtunei Hort. r!garis I.inn. Himanthine i3 (33) Berbamunine 1 (34) Oxyacanthine 48 (34) 'ponica Thunb. Berbamine 57 (34a) Oxyacanthine 48 (34a) Berbamine 57 (35) Isotetrandrine 62 (35) Berbamine 5i 13fi) Oxyacanthine 48 (36) Belarine 03 (37) Espinidine 8 138) Eepinine 9 (38) Lauberine 106 (39)

0-Methyl iaothalicberine 94 (3i, 39) Obnherine 46 (39) Berbamine 5i (39a) Berbamine 57 140) Isotetrandrine 6 2 (40) Berbamine 5 i (41) Isotetrandrine 62 (41) Berbamunine 1 (42)

Oblongamine 47 (42) 0x3-acanthine 48 (42)

66b (Pia)

ethyl berbamine 66a (42a)

Structural type of the

alkaloid

XXI xx I I XI11 VI VI VIII VI11 VIII XV XV VI VI VI11 XXIII VI VI XXIII XXI XXI VIII VIII VIII

VI11 I VI11 VI

VI11 VI11 v I

Cndetermined I VI

VI11 VI VIII VIII VIII VI XI I I XIV

XI VI VI11 VI11 Y I I I r111 VIII I V I 1 1 VI VI

J A N - F E B 19791 GUHA E T AL. : B I S B E S Z Y L I S O Q U I N O L I N E ALKALOIDS 9

TABLE 3. Continued. I

B. 2 'UlgQr lS Linn. . . . Root iB. heteropoda Schrenk, I *

B. zrbiliana ~ u x i r s semper:ireiis Linn.. . . . . . . . 1 Leaf

. . . . . . . . . .

IB. :.aliicbiana Baill.) See d b u l a

S a m e of the plant

Berbamine 5 i (46) Osyacanthine 48 (47) Berbamine 5 ; 4 i a j (')-Curine 132 (48)

cai id icans Sandwith

B. petiolaris Sal1 B. svaseyr Bucke)

B. thunbergri DC (Mahonia sbusq i Fedde)

B. tinitoria Leschen. . .

B. lschonoskyana Regel (B. aristda)

I Structural

Plant part Alkaloid studied

Root Root

Whole plant

Root

Stem

Berbamine 5; 112b) Berbamine 5i (43)

Berbamine 5 i (44) Isotetrandrine 62 (44) Oxyacanthine 48 (44) Berbamine 5 i ,331

Obaherine 46 (45) Obamegine i l 14.5) Ox;\-acanthine 48 (45)

Ch3ndodendron caiidicaiis Sandwit h C. 1imacii:olium (Dieis) Jloldenke.

C. miirofih:.lum (Eichl. 1 Moldenke. . . . iS~chnosr3al1rm miiroph>lliim Eich! )

C. platiph:,liirm IIiers . . . , . . . . .

C . tomeiitosiim Ruiz and Pavon

C. toxicojmiim ' n ' edd .~ Kruk. et Mold

Wood

Root

Leaf Stem, root and

Root and leaf Stem and barb

leaf

Stem

Stem and leaf Stem

Yamamoto] C. mucronafa d Rich C ocalifolia DC

Root I

Cissampelos iiisnloris JIakino . . , Root iParacgclea ivsularis Maliinol Kudo and

C. pareira Linn

Cocculus hirsxtus (Linn.) Diels

C . japonicirs DC.. C. laurifoliirs DC.

Whole plant Root

Root and leaf

I "

, Stem and root

Isochondodendrine 122 (49) i+ 1-Sore,-cleanine 124 (49, 50)

(+ -Curine 132 (20) Isochcndodendrine I22 1 0 ) Chondroioline 131 '20) (-)-Curine 133 (20)

Isochondodendrine 122 (20) Chondocurarine 129 (51)

ibaee B)

Chondrocurine 130 (60, 5 2 ) I- ]-Curine 133 (50, 5 2 , 53) Cycleanine 121 (50 , 5 2 ) Isochcndodendrine 122 150, 5 2 ) '--)-Tubocurarine 142 3 2 ) i-)-Sorcl-cleanine 124 (50) (-!-Tubocurarine 143 ' 5 3 ) Tomentocurine IS6 150) '-)-Curine 133 :W Isochondodendrine 122 (54) Tosicoferine 141 (54) C;\-cleanine 121 ( 5 5 )

Insularine l i 0 5 5 ) Isochondodendrine 122 (56 ) Dih5-dron-arifteine 146 1 5 i ) Dimethyldihydron-arifteine 147

t>Te of the alkaloid

Dimethl-lwarifteine 168 (57 ) JIethyldihydrorrarifteine 149 ( 5 i ) Jleth>-lnarifteine I50 ( 5 i ) Warifteine 151 (57) Cissampareine 145 i 5 S ) Insularine l i 0 (59) Isochondodendrine 122 (11, 59) 4"-O-\Ie:hylcurine 139 (60) (-]-Curine 133 110, 11, 60, 61) C;\-cleanine 121 f59, 6 1 ) Ha>-atidine 136 (61) Hayatine 137 (IO. 11, 61) Ha-atinine 136 110, A l l Isotrilohine 15; '62) Trilohine 163 (62)

~

See .Siefihania ~ jagoiiica 'Thunh.) Miers Bark and trunk 1 Isotrilobine 15; '63)

Trilohine 163 (63)

VI11 VI11

VI11 VI11 VI VI11

VI VI11 VI VI11 \' I

VI11 XXI

xx xx XXI xx XXI XXI

xx XXI XXI XXI xx xx XXI xx XXI

XXI xx XXI xx

L-ndetermined

1 XXll

1 XXll

1 XXI

XXll

XXll XXll XXVl

~ xx XXI

XXI XXI XXI

XXIII

XXlll XXllI

1 xx

1 XXlll

10 JOURSAL O F S S T U R A L P R O D U C T S [VOL. 42, NO. 1

TABLE 3. Coniznued.

S a m e 01 the plant

C. leaeba DC.. . . . . . . . . . . . . . . . . . . . .

C. pendulus (Forsk) Diels.. . . . . . . .

C. sarmentosu~ Diels

C. frilobus DC.

Colubrina asiatica Bronpn. . . . . . . . C . faralaolra . . . . . . . . . . . . . . .

Crcmastosperma polypklebum (Diels)

Cyclca barbata (Wall.) hfiers . . . . . . . . . Fries. . . . . . . . . . . . . . . . . . . . . . . . . . . . .

C . burmanni Hook. et Thoms . . . . . . . C . insularis (hfakino) Diels.. . . . . . . . . . . .

C . madngascariensis Baill.. . . . . . . . . . . . . . .

C. peltofa Diels.. . . . . . . . . . . . . . . . . .

Plant part studied

Root Leaf Stem and leaf

Root

All parts of the plant

Bark Leal, stem-bark,

root-bark

Bark Rhizome

Root Rhizome

Root

Root

Dapknandra aromatica F. 11. Bailey.. . . . . . . I Bark

D . dielsii Perkins.. . . . . . . . . . . . , B y k

I =

Alkaloid

Oxyacanthine 48 (64) bfenisarine 165 (55) Cocsoline I52 (65) Cocsuline 153 (66) Cocsulinine 154 (65) Pendine 178 (6fi) Penduline 72 (66) Pendulinine 179 (65) Isotrilobine 157 ( 6 i ) Jfenisarine 165 (67) Tetrandrine 76 ( 6 i ) Trilobine 153 (67) Coclobine 35 (68)

Isotrilobine 157 (59) Normenisnrine 166 169) Daplmoline 38 (69) Trilobine 163 (69) 0-Methyldauricine E a (69a) Cycleapeltine 36 (69b)

Limacine 64 (69b)

Phlebicine 25 (70) Homoaromoline 42 (71) Isotetrandrine 62 (71) Berbamine 5 i i i l a ) Chondrocurine 130 ( i 2 ) (*)-Fangchinoline 58 (73) (+I-Isochondodendrine 122 (74) Limacine 64 ( i la ) Monomethyl tetrandrinium 67 (75) (+I-Tetrandrine i 6 (74) !=t>-Tetrandrine 77 (71a) Tetrandrine mono-S-2'-oxide 78 ( i 2 ) Thalrugosino 79 (73) Tetrandrine 76 ( 7 6 ) Cycleanine 121 (77) Insulanoline 169 (77) Insularine 170 ( i i ) Isocbondodendrine 122 (781 (+)-Sorcycleanine 124 ( 7 ; ) Chondrocurine 130 (11) (-)-Curine 133 (11) Isochondodendrine 122 (11) Cycleacurine 134 (79) Cycleadrine 58 (79) Cycleahornine 59 (79) Cycleanorine 60 ( i s ) Cgcleapeltine 36 (79) Fangchinoline 61 (79, 80) Isochondodendrine 122 (80) (+I-Tetrandrine i 6 ( i 9 , 80) (-1-Tetrandrine 77 (80) Aromoline 31 (81) Daphnoline 38 (81) 0-hIeth:-lrepandine 45 (32) Repandinine 90 (82) (-)-Tenuipine 92 is?) Repanduline 169 (82) Pseudorepanduline 1 6 i (83)

Structural type of the

alkaloid

VI XXIV XXlII XXIII XXlV

Undetermined Vlll

Undetermined XXl l l XXIV VI11 XXIIl VI

XXIl l XXlV VI X X l l l I VI

VI11

IV VI VI11 VI11 XXI VI11 xx VI11 VI11 VI11 VI11 VIll VI11 VI11 xx XXVI XXVI xx xx XXI XXI xx XXI V l l l VI11 Vll l VI VI11 xx VI11 VI11 VI VI VI X X XXV xxv

JAS-FEB 19791 GUHA ET AL. : BISBESZTLISOQUISOLISE ALKALOIDS 11

TABLE 3. Continued.

S a m e of the plant Plant part etudied

D. micrantha Benth

D. repandula F. Muell. . . . . . . . . . . . . . !;llhnosperma rapandulum F. Muell.)

D. species . . . . . . . . . . . . . . . . . . . . . . D . species Dr-7. ..........................

D. species unnamed.

D. tenuipes Perkins

Dryadodaphne nomguineensis (Perkins) A. C. Smith , . , , . . .

Epinetrum cordifolium Mangenot and Mibge . . . . . . . . . . . . . . . . . .

E . mangenotti Guill. and Debray,

E . ri lbsum (Excell) Troupin

Guattrria megalopkylia Diels

Gy~ocarpus americanus Jacq.. . . . .

Heracleum wll ichi . . . . . .

Isolona pilosa Diels

(G. wquini Roxh.)

Bark

Bark

Bark Bark

Terminal twig and leaf

Leaf Bark

Luurelia semper7irens Tul.. . . . . Limacia cuspidata Hook. f . and Thoms.

Bark

Root

Root and leaf

Leaf, root Stem

Stem bark

Bark and leaf

Root

Trunk bark

Leaf Whole plant

L. obloiiga X ? r a . . ~ Khole plant I

Lindera oldhainii Hems:. . .Magnolia com~we.c.ca h s i m . . . . . . J J . fuscala . h l r , , , . . . . .

'.lfichr!io ; ; i c [ a t a Blume;

Leaf Bark Leaf

Alkaloid

Daphnandrine 3 i (82) .~,O-Dimethylmicranthine 156 (13) 0-Methylmicranthine I58 (13)

0-Methylrepandine 45 (821 Repandine 49 , 8 4 1 Repandinine 90 (82) Repandu!ine 168 (82, 841 Isotenuipine 6 i 165) Fangchinoline 61 (13) S,O-Dimethylmicranthine 156 (13) 0-Methylmicranthine 156 113) (+l-Sortenuipine 88 (13) Telohine 160 (13) 1,2-Dehydromicranthine 154 (83)

9,O-Dimethylmicranthinr 156 (63) 0-Methylmicranthine 158 (53) Micranthine 159 (33) Pseudorepanduline 167 (63) (+)-Tenuipine 91 183) (-1-Sortenuipine 69 (82, 66) Aromoline 31 (82) (+)-Sortenuipine 68 (86) Repandmine 90 (66) Repanduline 168 (82) (-)-Tenuipine 92 (62) (+)-Tenuipine 91 (86)

Drs-adine 104 ( 6 i ) Dryadodaphnine 105 ( S i )

Cycleanine 121 (88) Isochondodendrine 122 (85) Sorcrcleanine 124 (68! Cycleanine 121 f68) Isochondodendrine 122 (88) Sorcrcleanine 124 185) Cycleanine 121 M a ) Isochondodendrine 122 f86aj Xorcycleanine 124 ;RSa 1

0,O-Dimethylcurine 135 (69) Isochondodendrine 122 169) 12'-0-Meth>-lcurine 140 (391 Phaeanthine i4 (90) Pycnamine i 5 190, Crcleanine 121 '90a) Isochondodendrine 122 i9Oa) Curine 133 ((rob\ Isochondodendrine 122 r9Oh)

Limacine 64

Limacine 6 1 ,Q3 Limacusine 44 '9.3' Lindoldhamine 11 94 0s)-acanthine 48 ' 9 5 Maqnolamine 15 '1; 1Iornoline 12 ,I;,

Structural type of the

alkaloid

VI XXIll XXIIl XXlIl VI VI VI X XXV X VI11 XXlll XXllI X XXlll XXlII

XXIII XXlll XXIII xxv X X VI X X XXV X X

XIV XIV

xx xx xx xx xx xx xx xx xx XXI xx XXI VI11 VI11 xx xx XXI xx VI11 I V I I I VI I V l l l 1' I I \ ' I I I I

12 JOURNAL OF NATURAL PRODUCTS [VOL. 42, NO. 1 TABLE 3. Continued.

M. borealis Takeda., . . . . . . . . . . . . . . . . . . M. fortunei (Hort.) Fedde.. . . . . . . . . . .

-If. grif i thii Takeda.. . . . . . . . . . . . . . . . . . . .

M. japonica DC.. . . . . . . . . . . . . . . . . . . .

(Berberis fwtunez Lindl.)

Root Trunk

Bark

Trunk and root Trunk, root and

M. manipurensis Takeda . . . . . . . . .M. morrisonensis Takeda.. . . . . . .

.\I, philippinensis Takeda

Ai. sikkimensis Takeda. . . . . . . . . . .if. simonsii Takedx.. . . . . . . . .If. s;iaseyi Fedde . . Mmispermum caiiadense Linn. . . . .

.\I. dauricum DC.

.I.ichelia fuscala Blume. . . . . . . . . . . . . . . . Necfandra rodiei R . Schomb.. . . . . . . . . .

(Ocorea rodiei)

Selumbo nucifera Gaertn .

Semuaron Tieiilardi Baill. Ocofea rodiei . . . . . . . . . . . . . . . . Pachygoxe pirhescens Benth.. . . Paracyclea insularis (Makino) Kudo and

P. ochiaiana (Tamamoto) Kudo and Yamamoto . . . . . .

Pamamoto. . . . . . . . . . .

Phaeanthus ebraceteolatirs (Presl) Jlerrill.. .

Pleogyne cuntiinghamii X e r s . . . . . . . . . . . (P. auslralis Benth.)

Root R w t

Trunk and root

Stem bark Root

Leaf Stem, root and

Rhizome

Rhizome

See Berberis

rhizome

See Jfagnolia Bark and Seed

Bark

Seed

Root Embryo

Bark and Leaf

Root and top See Xectandra

See Cissampelos

Stem, root and rhizome

Bark

Root

Alkaloid

Oxyacanthine 48 (96) Berbamine 57 (97) Oxyacanthine 48 (98) Berbamine 57 (15) Oxyacanthine 48 (15) Berbamine 5 i (99) Oxyacanthine 48 (99) Berbamine 57 (15) Isotetrandrine 62 (15, 19)

Oxyacanthine 48 (100) Berbamine 57 (101) Isotetrandrine 62 (101) Oxyacanthine 48 (100) Berbamine 57 (101) Isotetrandrine 62 (101 j Berbamine 67 (102) Isotetrandrine 62 (102) Oxyacanthine 48 (100) Oxyaranthine 48 (98) liaseji Buckley S o alkaloid (18) Dauricine 3 (18, 103)

Daurinoline 6 (103) 3”-Desmethyldauricine 7 (103) Dauricine 3 (104, 105) Dauricinoline 4 (105) Dauricoline 5 (104) Daurinoline 6 (104) ucata Andr. Ocotine 23 (106) Rodiasine 26 (106. 1 O i ) Sepeerine 50 (107) Demerarine 39 (107) Dirosine 19 (107) Norrodiasine 22 (107) Ocodemerine 176 (107) Otocamine l i i (107) Z-Kor-(i)-tetrandrine 70 (106) Ocotosine 24 (106) (+)-Curine 132 (48) Isoliensinine 28 (108) Lienrinine 29 (109, 110) Neferine 30 (110) Seumarine 111 (111) idiei R. Schomb. Isotrilobine 157 ( l l l a )

mclaris Makino

(-)-Curine 133 (112)

Cscleanine 121 (112) Insularine 170 (112) Isochondodendrine 122 (112) Phaeantharine 73 (113) Phaeanthine 74 (114) (-)-Curine 133 (115) Isochondodendrine 122 (115)

Structural type of the

alkaloid

VI VI11 VI VI11 VI VI11 VI Vl l l V l l l

VI VI11 VIll VI VI11 VllI VI11 VI11 VI VI

I

I I I I I 1

IV I V VI VI IV IV

Cndetermined

VI11 IV XXI V V V XVI

X X l l I

XXI

xx XXVl xx VI11 VI11 XXI xx

JAN-FEB 19791 GUHA ET AL. : BISBENZYLISOQUINOLISE ALKALOIDS

TABLE 3. Continued.

13

Same of the plant Plant part studied

P>ciiarrheiia ausiraliana F. Muell.

P. manilleiuis F. Muell.

Khole plant in- cluding root

Root

P . omatha Diels . . . . . . . . . . . . . . . . . Bark

Sciadoleiila tcxijera Krulioff and -1. C. I ' Smith . . . . . . Stem

Siephaizia c a p i t a t i Spreng.. . . . . . . . . . . . .

S. cepharanlha Hayata. Root tuber

5. diiabelagci Diels , , , . , . Root and stem S. discolor Spreng. . . . . . . . . . . . . . . See S. S. glabra i,Roxb.'~ Miere . . . . . . . . . . . . . See S. S. hwizaiidifoiia (Killd.) Walp., , . , . , , , , . , ~ Root

iS. discolor Spreng.)

3. lapoirica 1Thunb.) Niers.. , , , , , . , , , . , . Root, stem and leaf

Root and terres- terial portion

Stem and leaf Tuber and above

ground parte S. rotirrzda Lour.. . . . . . . . . . . . . . . . . . . . . . . .

S. sasaiii Haj-ata . . . . . . . . 15. glabra rRozb.) lliers] ' Root

I ' Tuber

S?chiiosepali~m microphillum Eiohl.. . . . . . . See Choiidodeizdron Thoiictriim dcsjcarpiim Fisch. and La11 , , Root T.feiid1eri C. L. Anders. Khole plant

T.,foetidum Lim. . . Aerial parts

~ Root

T . glauciim Desi. , , . , I See T . T. hertiaiidezi: Tauech.. . . . Root T . isopjroide? C. -1. )ley.. . . . . . . Root

Alkaloid

Berbamine 5; (116)

Isotetrandrine 62 I 116) 2-S-Sorberbamine 69 (116) 2-S-Sorobamegine 69 1116) Berbamine 57 11171 Isotetrandrine 6 2 111;) Phaeanthine 74 '11;)

S, St-Bienoraromoline 32 111 5 ) 2-.\--Sorobamegine 69 ill@',

Sciadenine I 2 7 '119) Sciadoline 128 (1203 Cj-cleanine 121 (121) f-i.)-Epistephanine 40 :l22) Berbamine 67 (123) Cepharanoline 33 (123) Cepharanthine 34 (55 , 123) CJ-cleanine 121 155, 123) Isotetrandrine 62 ;55, 123) Dinli!a!eine 172 (124 I

reriioiiii,kdia Kalp. .oiir i ida Lour. Fangchinoline 61 126) Isochondodendrine 122 '125) Isotrilobine 157 (126) (-:-Tetrandrine ;A ,125) i+,-Tetrandrine 7 7 (125) Oxoepistephanine 4 i a il26a) Epistephanine 40 ( I E , 128)

Hj-poepistephanine 43 (12;)

Obamegine i l (129) Insularine 170 (130) Stebisimine 51 '128) C:-cleanine 121 (16 )

Berbamine 5; (131)

Tetrandrine 7 6 1132) microph!llum Eichl.

Berbamine 57 (1

Thalfoetidine 99 '136) Thalfine 102 '13 iN Thalfinine 103 (137)

Hernandezine 81 1381 0-Methj-Ithalieopine 55 1139) Thalisopirline 53 1139) Thalisopine 54 (1%)

riigosio71 Ait.

Structural type 01 the

alkaloid

V I l l

\ ' I l l V l l l V l l l VI11 VI11 V l l I V l l l

Cndetermined

VI VI I I

xx xx xx VI V l l l VI VI xx VI11

Cndetermined

VI11 xx XXIl l VI11 VI11 \ ' I VI

VI

V l l l XXVl VI xx V I I I VI V l l l VI11 V l l l VI11

XI1 IX IX V l l l V l l I XI1 Xl l l XlIl

XI VI1 VI I VI1

14 JOURSAL OF S - 4 T U R A L P R O D U C T S [VOL. 42, KO. 1

T ~ B L E 3 . Contitwed.

Kame of the plant

T . longistglum DC. . . . . .

T . lucidum,, . . .

T . minus Linn

T . pedunculatum Edgew. . . . . . . . . . . . . . T . podocarpicm Humh. . . . . . . . . . . .

T . polygamum Muh.. .I.. . . . . . . . . . . . . . . . . T . reaolutum DC. . . . . . . . . . . . . . . . . . . .

T . rochebrunianum Franch & Sar.

T . iugosum .lit, , . (T . glaucum Desf.)

Plant part studied

Root

Root

Ahore ground parts

Root and whole

Root plant

Whole plant

Root

Root

Root

Root

Aerial part

Alkaloid

.V-Desmethylthalistyline 16 (140) Methothalistyline l i (140) Thalibrine 14 (140) Thalists-line IS (140) hromoline 31 (141) Homoaromoline 42 (141) 0-llethylthalicherine 95 (141) Ohaherine 46 (141) Ohamegine 71 (141) Oxyacanthine 48 (141) Thalicberine S i (141) Thalidasine 100 (141) Thalrugosine 79 (141) 0-Methylthalmethine 56 (142)

Thalmethine 98 (142) 0-l\lethylthalicberine 95 (142, 143.

Ohaherine 46 ‘144a) Thalfine 102 (144a) Thalfinine 103 (144a) Thalieherine S i (142) Thalidasine 100 (144a) Thalideaine 83 (143) Thalirahine l i a (144a) Thaliracebine 14a i144a) Thalrugcsaniinine 55 (144a) Thalmine 108 (144) Berbamine 5 i (14.5) S-Desmethylthalidezine 80 (146) l--Desmethylthalistyline 16 (146) Hernandezine 81 (146) Isothalidezine 82 (146) hlethothalistvline l i (146) Thalidezine 83 (146) Thalistyline 18 (146) Thalrugosine 79 (147) O-hfeth>-lthalicberine 95 (148) 0-hlethylthalmethine 96 (148) Thalidasine 100 (148) Thalrugosaminine 55 (148) Hernandezine 81 (149) Sorthalihrine 13 (150) Thalihrine 14 (150) Thalihrunimine 112 (151) Thalihmnine 113 (149) Thaleimine 86 (151) Obamegine 71 (152) Thalidasine 100 (152) Thalideaine 83 (143) Thaligosidine lOOa (152a) Thaligosine 62a (152a) Thaligosinine 52b (152a) Thalirugidine l ia (152a) Thalirugine 14a (152a) Thalirupinine 14h (152a) Thalrugosamine 52 (153) Thalrugosaminine 55 (154) Thalrugosidine 101 (152) Thalrugosine i 5 (152) Thalsimine 86 1143)

144)

Structural type of the

alkaloid

111 111 I 111 VI VI XI VI VIII VI XI XI1 VI11 XI

XI XI

VI XI11 XI11 XI XI1 IX 111 la V I I XIV VIII IX 111 1x IX 111 IX 111 VIII XI XI XI1 VI1 IX I I XVlI XVII IX VI11 XI1 IX XI1 VI1 VI1 111 la la VI V I I XI1 V I I I IX

J A S - F E B 19'791 GUHS E T BL. : B I S B E S Z T L I S O Q U I S O L I S E S L K S L O I D S 15

TABLE 3. Contimied.

I

XVIII XVI I I VI11 VI11 VI11

XIX I XVlll

XVI I I XVlll XVlll

Endetermined L-nderermined

XXIII VI11 VI XXIII XXl lI VI11 XXIII

rndetermined

1 \ I l l

~

~ studied S a m e of the plant Plant part

T . mbcordaia Olir.

T . simplex Linn.

Root, stem and leaf

Leaf Root

T . sir l lannbcdri ir~

T . thioibergi i DC. . . . . . .

Aerial part

Aerial part and

Aerial part

Root

seed

~ Stem and leaf

Tilincova Oiiihlaget Enpl. Root I " l u

~'

Alkaloid

_ _ Hemandezine 81 115.5) Thalidezine 63 (15.5) Thalisamine 84 (155) Thalsimidine S5 (156) Thalsimine E6 (155, 156, 157)

Hemnndezine 81 115ia) Thabadensine 106a il57a) Aromoline 31 (1.58, 159) Homo~romoline 42 (158, 159) 0-Uethylthalicberine 95 (160) Thalicherine S i (160) Thalictine 1Oi (161) Dinklacorine 111 (162) Funiferine 20 (163') Xortiliacorinine .I 116 (163) Tiliacorinine 119 (163) Tiliageine 2 ; (163) Funiferine 20 1164) Funiferine S-oxide 21 (165) Sortiliacorine A 115 (166) Sortiliacorinine .1 116 1166) Tiliacorine 118 '166) Isotetrandrine 62 1166a) Thalrugosine i 9 (l66a) Tiliafunimine i9a (16fia) Tiliacoridine 183 1167) Tiliamosine 120 :163) Sortiliacorinine -1 116 1168, 169) Xortiliacorinine B 11; 1169) Tiliacorine 118 (169) Tiliacorinine 119 1169) Tiliarine 185 (170) Tiliandrine 184 '74) Cocwline 153 ' l i l ) Isotetrandrine 62 ( l i l ) Stebisimine 51 i l i l ) Trigilletimine 162 (172) Cocsuline I53 (171) Pl-enamine i5 ( I i l ) Trigilletimine 162 ( l i 2 ) Phaeanthine i1 (171, 173)

i Aromoline 31 ( l i d ) 1 Fangchinoline 61 (lil)

Tetrandrine 76 rli4) Tricordatine 161 (lis) Chondrofoline 131 (li5a) Obamegine i l 1176)

Oxyacanthine 18 , l i 6 ) i

I Structural t j p e of the

a 1 k a 1 o 1 d

IX -

~ ::: 1X

I 1x

the detection of phaeanthine in Triclisia patens; Bhatnagar ( lSl) was partly success- ful in identifying and characterizing a large number of BBI alkaloids. Dragen- dorff's reagent, or a mixture of an aqueous solution of chloroplatinic acid and aqueous potaqsium iodide, n as found to be unsatisfactory because of rapid fading of the colored spot<: a solution of iodine in potassium iodide was prescribed.

After determination of the number of alkaloids, the tertiary alkaloid mixture is

16 JOURNAL OF KATURAL PRODUCTS [VOL. 42, NO. 1

treated to separate the individual components. A number of procedures have been developed.

The crude alkaloidal mixture contains in most cases both phenolic and nonphenolic bases, and only the tertiary BBI bases containing two -OH groups show common phenolic properties2 Bick et al., after extracting the phenolic bases with 5% sodium hydroxide solution, evaporated the chloroform solution of the tertiary alkaloids to dryness, dissolved the residue in benzene, and then extracted the cryptophenols Tyith Claisen reagent (13).

Cava (54) and Grundon (182) applied a modified technique to separate phenols from other bases. The acid solution of total alkaloids was made strongly alkaline m-ith 10% sodium hydroxide solution. After removal of the non-phenolic and cryptophenolic bases by chloroform extraction, the alkaline solution it-as brought to pH 8 by the addition of ammonium chloride; the phenols were then extracted with chloroform.

Countercurrent distribution of the alkaloids betn-een chloroform and buf- fers of different p H has also been used to separate the BBI bases of different acid constants (106, 169). Fong, using benzene, (149) extracted the alkaloids of Thalictrum rochebruiziaitum from its acid extract at pHs 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 7.3 and 8.8.

The separation of alkaloids by distribution among different solvents is also a common process. Remarkable success has been scored by Iiupchan (79) by distributing Cyclea peltata alkaloids among glycol, benzene, heptane and methanol.

The different fractions separated as above (a, b or c), are then chromatographed on an alumina column, activated (169) or deactivated (76), or on silicic acid. Flori- si1 (134) and diatomaceous earth (103) have also been used on several occasions. Solvents used as eluents are benzene, ether, chloroform, ethyl acetate. methanolic benzene, methanolic chloroform, etc. There are also reports of the use of di- chloromethane, but it has some disadvantages; type IV alkaloids showed evi- dence of some decomposition (107), and Iiupchan (79) separated a large number of artifacts formed by reaction of the natural alkaloids with dichloromethane.

Partition chromatography n-as reported to separate obamegine and oxy- acant hine from the alkaloidal mixture of X a d z o r h i z a simplicissima (1 76) .

Preparative thin layer chromatography has also been used (13, 61, 79). On many occasions the bases were separated as their salts or some other deriva-

tives. Shanima (135) converted the crude alkaloid mixture of Thalictrum feizdleri to hydrochlorides and separated the individual hydrochlorides by partition chro- matography on a cellulose column using methyl ethyl ketone-water as eluent. On the other hand, Bick (13) isolated 0-methyl micranthine and telobine as their K-acetyl derivatives.

Minimal work has been done on the isolation of quaternary BBI alkaloids. Tubocurarine chloride n-as iqolated by King ( 2 5 ) from Afzomospermum graltdi- foZiunt. After the removal of the tertiary bases, the quaternary bases n-ere pre- cipitated from a weakly acidic solution of the alkaloids as reineckates, which were then converted into chlorides, and the solution upon concentration gave crystalline (+)-tubocurarine chloride. Recently, Iiupchan (79) used two ion exchange columns, Don-ex 1-X8 (OH and C1 forms), m-ith methanol as eluent to separate cycleanorine and cycleahornine chloride.

a)

b)

c)

Tompounds containing one -OH group, sometimes called cryptophenols, differ from the former in that they are usually insoluble in sodium hydroyide solution, but soluble in Claisen reagent (25% methanolic potassium hydroxide solution).

JAS-FEB 19791 GCHA ET AL. : BISBESZTLISOQCISOLISE ALKALOIDS 17

STRI-CTCRAL ELUCIDATI0S.-For many years little progress n-as made in the elucidation of the structures of the BBI alkaloids, principally because in almost every case erroneous 'monomeric' formulas (C1,-C20) TI ere assigned on the basis of wrong molecular weight determination.. Although Pyman (183) in 1914 assigned formula C d . & to the three alkaloids of Daphizavdra micraiztha Benth., he failed to determine their structures. The structure elucidation of the BBI alkaloids x i s pioneered by Spath and Kolbe ( A i ) who in 192.5 suggested a 'dimeric' formula (C37) for Oxyacanthine for n hich a monomeric formula had been previoubly accepted. I n the follon ing decades the formulas of the other BBI alkaloids were similarly revised. Honever, not until the application of mass spectrometry to this laby- rinthine problem could the chemists obtain accurate molecular weights and com- positions since these alkaloids have a tendency to retain the solvent of crystalliza- tion even after drying at a very low pressure. Improved degradation methods and nuclear magnetic resonance spectroscopy including double resonance and nuclear Overhauser effect studies (16s) have proven of great value in solving many of the srructural problems such as the location of substituents and the determi- nation of the configurations of the chiral centers.

A brief discussion on the important degradation reactions applied to the BBI alkaloids n-ould help researchers in this field because the spectroscopic data alone are still insufficient to predict the structure of a new BBI molecule.

Permanganate oxidation.-The methylene groups (a and cy1 position in I, table 1) n-hich are both benzylic and /3 to nitrogen atoms are susceptible to facile oxidation by an aqueous solution of potassium permanganate. But identi- fication of the degradation products cannot always lead to a single structure for the parent molecule. For example, the expected degradation products 1 and 2 of isotetrandrine (VIII,3 R f = R 3 = R 4 = R j = R S 1 = R 3 ' = M e , R1=R1 '=H ) are also possible from obaberine (VI, R2 = R3 = R4 = R2' = R31 = R4I = Me, R1 = R1' = H ) and their stereoisomers.

a)

1 2

Shamma (184) has developed a controlled oxidative method with potassium permanganate in acetone. Cleavage occurs, irrespective of the configurations of the chiral centers, a t the benzvlic bond of the isoquinoline moiety, n-hich is un- substituted at CS' (or C,) producing a tertiary lactam and an aromatic aldehyde. For instance, oxyacanthine (VI, R1 = R3 = R, = R31 = R4I =Me, R4 = H, R1 = R1 = H ) gives baluchistanamine (3), a natural product.

U

OH

3

3The Roman numerals used in this discussion refers t o the structural type depicted in Table 1.

18 JouRs.4L OF SATURAL PRODUCTS [VOL. 42, NO. 1

The aromatic proton signals in the nmr spectra of BBTs generally overlap and are difficult to assign. On the other hand, the signals of the oxidized products are spread over a large range and are generally eaqier to identifj-. Phenolic compounds are oxidized as their 0-acetates to get better yields. This controlled oxidative method, although of low yield, should assist in the elucidation of the structures of BBI molecules.

b) Hofmann degradation.-The process is illustrated Jvith 12-0-ethyl oxyacanthine (VI, R ~ = R ~ = R z ' = R ~ ' = R 4 ' = 1 I e , R1=Et , R1=R1'=Hl 1 ) in scheme 1.

12- 0 - Ethyloxyacanthine

1. C H 3 I 2. Hofmann deg r odat ion wi th alkali and heat

3.0zonolysis

1. C H ~ I

2. H ofm ann. degradation

1. Pt/ H q

2. Zn/Hq 4

Scheme 1 . 5 - Here again, a single structure cannot be predicted. Stereoisomers of the

12-0-ethyl derivatives of oxyacanthine and berbamine (8, R = H) can give these degradation products, namely 4 and 5.

I n spite of its demerits, the Hofmann degradation is still used for the BBI molecules containing a biphenyl unit (Types IV, XVIII and XIX) where the metal- ammonia degradation (discussed later), the most widely used degradative method of structure elucidation of BBI molecules, is ineffective. The newly developed methods, photolysis (discussed later) and controlled oxidation with potassium permanganate, could supplant the Hofmann degradative method in the near future.

JdS-FEB 19791 GUHA ET -4L. : BISBESZYLISOQUISOLINE ALK4LOIDS 19

Photolysis.-Bick (185) has observed that BBI alkaloids on irradiation with uv light in the presence of oxygen undergo cleavage at the C-1 and C-1' benzylic centers. Isotetrandrine (VIII, R2 = R, = R, = R j = Rpl = R31 = JIe, R, = R1' = H 1 1 ) gave the amide carbinolamine intermediate 6 and the dialdeh>-de 7 as the major products.

c)

The method is illustrated in scheme 2 .

I s o t e t r a n d r i n e

6 - I

L

S c h e m e 2

It has been observed that the lactam is formed on that isoquinoline unit n-hich

The presence of phenolic groups complicates the reaction and diminishes the

d) Metal-ammonia reductive degradation.-Sowa (186) in 193'7 cleaved

is unsubstituted at Cs or Cs'.

yield; these are, therefore, methylated or ethylated before irradiation.

diarylethers reductively with sodium in liquid ammonia.

S a 'liq.SH3 Ph-0-Ph +PhOH+PhH

Alk>-l aryl ether linkages remain mostly unaffected. Substituted diary1 ethers can cleave in two n-ays.

Cleavage

at b

Sowa made a systematic investigation (186, 187, 187a) on different substituted di- arylethers to Gtudj- the effect of subqtituents on cleavage pattern and obqerved that the fission of the bond betu-een oxygen and the substituted ring (cleavage at a) is promoted by substituents in the order o-Ale0 > m-JIeO > m-Ne > p-OJLe.

20 JOCRSAL OF S A T U R a L PRODUCTS [VOL. 42, NO. 1

53 70 99%

Ph-& - -PhOH

55YG (The yield of the predominant phenol only is indicated).

Scheme 3

In 1951, Tomita first applied this reaction successfully to cleave BBI molecules into two B I molecules. He isolated a phenolic B I 9a and a non-phenolic B I com- pound 9b from the reaction mixture formed by the reaction of 0-methylberbamine (8, R = M e ) in toluene with sodium in liquid ammonia (188).

'Q Na 9a ts a$ Li? NH, -

R 0'

e S c h e m e 4

-

The reaction has been applied to a large number of BBI molecules, and it has been observed that the direction of cleavage is determined by the substitution pat- tern in the aryl rings (scheme 3 is generally obeyed); the conformations of the molecules appear to be less important in influencing the cleavage pattern. The case of 0-methylberbamine (8, R=ilIe) is illustrated in scheme 4.

K3 a : R2=Me,R4=OLle,R~=R~=OH,R3=R6=Ri=H,Rl=H, b : R2=Jle ,R4=Rj=Rs=OMe,R3=R6=Ri=H,R1=H~l c : R 2 = M e , R 4 = R , = O h l e , R ~ = O H , R ~ = R ~ = R i = H , R 1 = H , d : R2=I\Ie,R4= Rs = Ohle,Rj = OH,R,= R6= Ri= H,R1= H 1 e : R2=Ale,R4=Rj=Ohle,Rs=OH,R3=D,Rs=Ri=H,RI=H, f : R2 = Me, Ra = Rs = OMe,Rs = OH, R3 = E, = D, R6 = H,R1 = H 1 1

g : R2=XIe,R4=R,=Ra=OPvIe,R~=Ri=D,R3=H,R,=H 1 h : R2 = l l e , R j = OMe,R4 = R = OH,R3 = R5 = R = H,R1 = H,

R z = Rle,R4 = R, = OIvle,Rs = OEt,R3= R,= Ri=H,R1 =HI 1 1 Rz = Me,R4 = Rb = OMe,R3 = Rj= Rg= Ri = H,R, = H, Rz=Lle,R4 = Rs = OMe,Rj = OH,R3= Rs= R;= H,RI = H,

1 : R2=Me,R4 = Ra = OMe,Rs = OH,R,= R, = R; = H,RI = H, m : R 2 = hle ,R4= R,= OMe,Rs=Me,Rs=R6= Ri=H,RI = HI 1 n :R4=R6=OMe,Ro=Rs=OH,R2=R3=Ri=H,R~=H o : R? = Me,Rj= RE = OH,R3= R4= Rs= R; = H,R1 =H,

R2 =ble,Ra = Rs = Rs =OMe,R3 =Rs = Ri =H,Rl = H, R2=Rle,R4= Rs=Ohle,Rg= R*=OH,R&= R i = H,R1= H, R2=Me,Ra=Rs=RB=OiLle,R~=OH,R~=R;=H,R1=H, R2=ble ,R4= Rs = Rs = OMe,Ri= OH,R3= Rs= H,Rl = H 111 R2=Me,R3=OEt ,R4= Rj = Rs=OMe,Re=Ri=H,R1=H, R 2 = hle,R3=OEt,R,=R~=OMe,R4= Re= R-=H,Rl=H, R2 = Me, R3 = Rs = Ra = OMe,R4 = R5 = Ri = H,R1= H b

h-@f

RE

9

w : R4=OMe,Rs=Rg=OH,R2=R3=Rg=R,=H,R1=H x : Rz = Me ,R4 = Rs = OMe,Ra = OH ,R3 = R 6 = R, = H,RI = H,l'

J r l S - F E B 19791 GUHA ET AL. : B I S B E S Z T L I S 0 Q I ; I N O L I S E ALKALOIDS 21

Since the chiral centers are not involved in this reaction, the configurations of the asymmetric centers of BBIs and their degradation products are identical.

Definite conclusions about the sites of attachment of the ether linkages are not aln a)-s made possible by simple sodium-ammonia cleavage. For example, the degradation products 9c and 9d from 0-methj-loxyacanthine (VI, R 2 = 1x3 = R, = R2'=R:, '=R4'=I\Ie; R1=R1 '=H j suggest the alternate structure 10 also for 0-methyloxyacanthine.

10

To solve the problem, Inubushi (189) deuterated the BBI molecule under condi- tion$ 71-here only the protons ortho to methoxy groups were deuterated before cub- jecting them to reductive degradation. The method is exemplified in scheme 5 . The presence of deuterium at C5 in 9e indicates the original ether linkage betn een C, of 9f and Cs of 9e. The deuterium at C11 in 9f diem the terminals of the other diphenyl ether linkage to be at C13 in 9f and at C1: in 9e.

Oxyacanthine

(VI, R z = R3 = R;= R;= R;=Me, R~=H,R,=R;=H 111 1 I) 0-Methylation 2) Treotrnent wi th

34/.DCl in D l 0 D i D

Scheme 5

However, extension of this deuteration procedure to another alkaloid nemuarine (XVI, R2=R3=R4=R2'=Rs1=lIe .R5=H,R1=H ,R1'=Hb) resulted in the introduction of only one deuterium, at position C s ( l l l ) , although both Cs arid Cgl, ortho to methoxy groups n-ere expected to be deuterated.

Bick (3'7) suggested an alternative method; the cleavage was done m-ith *odium in SD3 instead of ammonia; deuterium marks the terminals of the ether linkage. Bick determined the structure of 0-methylisothalicberine (SI, R2 = Rs = R4 = R 5 = Rgl = R: =Me, R1 = R1' = H,l j from the fission products 9g and 9h.

The position of the phenolic function can be determined by degrading the 0-ethyl derivative with sodium-ammonia. Bick (2s) found that the non-phenolic cleavage product of 0-ethj-lberbamine is 9i, thus indicating 8 ( R = H j a< the structure of berbamine. A recent method is to cleave the trideuteriomethyl derivative of the compound (23, 150). Application of this method seems to be

22 JOURNAL OF KATURAL PRODUCTS [VOL. 42, NO. 1

on the increase since several phenolic BBI alkaloids react n-ith diazoethane very s10wlj- making the preparation of their 0-ethyl derivatives difficult.

When a diphenylenedioxide bridge is present in a BBI molecule, a tn-0-stage reductive fission is required, as illustrated with isotrilobine (XXIII, Rz = R3 = Rz '=R3 '=h le , R 1 = H b , Rl '=Hl I) inscheme6 (190).

Isotri l o b i n e

Na, N O H Lio. N H 3 I

I . C h Z N 1

2 . N a / L i q . N H 3 1 9j t 9~ t9-t - -

Scheme 6

The phenyl-benzylether linkage cleaves with metal-ammonia in the following way :

Ph-0-CH2Ph +Ph-OH+ CH3Ph

For example, 0-methyl cisampareine (11, R = M e ) is reduced according to scheme 7 (191).

11 s c h e m e 7

I n the above scheme the -C=K-group is reduced during this reductive clea- vage. Some other chromophores are also known to react with sodium-liquid am- monia, e.g., > C = 0; methylenedioxy groups can be hydrogenolyxed and con- verted to a single phenolic group. For example, cepharanthine yielded 90 as one of the two degradation products (192). Cepharanthine IYa/liq. S H 3 (Rz = R3 = RA = Rz' = Me, R'a-R'4 = CH2, R1 = R1' = H I 1 1 )

The hetero ring of the isoquinoline containing a quaternary nitrogen is opened up during metal-ammonia reduction. For instance, a non-phenolic, optically inactive Emde-type degradation product 13 is produced from one quaternary half of 0,O-dimethyl(+)-tubocurarine acetate (12, R=A!Ie, X=OAc) (193).

+9d+90

Sodium in liquid ammonia has certain limitations : (1.) A complex mixture of more than two BIs can be produced, especially

Icupchan from BBI alkaloids having similar substitution around ether linkages.

JAS-FEB 19i9] GUHA ET AL. : BISBESZTLISOQCISOLISE ALKALOIDS 23

' - I e : N P g H < o

-%+ N Q F2Ng ' O p e

' OMe

13

,' d,Me 2X- 'H \ ' R nee' I

- 12 -

(194) separated the four products 9c, 9p, 9q and 9r from the reductive cleavage of thalidasine (XII. R2=R3=RA=R;=R2'=R3'=R4'=l1e, R 1 = H b , R1'=H ).

For example, tvio BIs 9b and 9s were isolated following sodium-ammonia reaction of thalfine (14).

( 2 . ) The cleavage pattern shown in scheme 3 is not qtrictly obeyed.

b 14

Scheme 8

(3.) Some methosyl groups are hydrogenolysed during the reaction. For ex- ample, 0-ethylthalidezine (IS, R2 = RA = R S = R6 = R2' = R3'= Me, R3 = Et, R1 = H b , Rl '=H j on sodium-ammonia reduction provided, along with the usual non-phenolic degradation product 9t, the demethoxy derivative 9u (133). Similar reduction was also observed in the case of hernandezine (IX, RP = R3 = R A = Rj = R6 = RP' = R,' =Ale, Rl = H b , R1' = H ) which by hydrogenolysis of C6-01\Ie led to the formation of 9v (196). During the degradation of dihj-drothalsimine (E), the C5-OI\Ie was hydrogenolysed (13ij 196) forming 9b as one of the products.

15 Scheme 9

Sodium-ammonia reduction hydrogenolpzes the CS-OH of thalisopine (1-11, Rz = R4=Rj=Rz'=R3'=R4'=Ale, R2=H, R1=Hb, R1'=H ) so that 9x is pro- duced as one of the degradation products (197).

S a liq.SH3 Thalisopine -9x+9k

e) Bick et al. (197a) observed that the BBI alkaloids are cleaved quantitatively

by ceric ammonium nitrate; the products after reduction were as a diamine and a diol. The process is illuqtrated in scheme 10 lyith hernandezine as an example.

Oxidative degradation n-ith ceric ammonium nitrate.-

24

Scheme 10

The reaction mas applied to a number of BBI alkaloids with success. Vhen applied to berbamine, thalicberine, and tenuipine, this reaction gave good yields of the nitrogen-containing fragments only.

This includes structures showing configurations a t the chiral centers, molecular formulas, and calculated molecular weights, melting points and specific rotations, as well as uv, nmr, and mass spectral data, and cd and ord information. The degradative methods used and the botanic sources are also given in table 4. The intent is to provide the re- searcher who has isolated a BBI alkaloid with a quick means of deciding xvhether his alkaloid is old or new and, in the latter case, of formulating a structure by correlat- ing its spectral data with those of the known compounds listed here.

The alkaloids are grouped in this table according to table 1. They are ar- ranged in alphabetic order, and the structures are described according to the skeletal structures of table 1.

Unless stated otherv-ise, uv spectra were obtained in methanol or ethanol, nmr in deuteriochloroform, ord and cd in methanol.

The symbol [a] used in this table actually means [ a ] ~ . Melting points are expressed in "C, optical rotations in degrees, chemical shifts in the nmr spectral data in 6 units, wavelengths in nm. Uv spectra are described as A max (log E). cd as [+I x (m.velengths at which the peaks and troughs appeared), mass as m/e (relative abundance). (wavelengths at which the peaks and troughs appeared) ; only in few cases are they described by the ampli- tude 'a' of the first Cotton effect and the [+] x lop2 value of the first extremum of the second Cotton effect. This diversity in describing the ord was unavoidable.

The reference number placed after the name of an alkaloid refers to the pub- lication related to the establishment of the final structure of the alkaloid. The reference to both the melting point and optical rotation is the same and is placed after the optical rotation value.

.1CKNOWLEDGERIEST

A complete list of the BBI alkaloids follows (table 4).

Ord curves are expressed as [$] x

The authors are grateful t o Professor Maurice Shamma, The Pennsylvania State Vniver- sit>-, U.8 .I., for his intereqt, constructive criticisms and valuable suggestions. They are thankful t o Professor I. R . C. Rick of the University of Tasmania and Dr. R. C. Das, C.S.R.S.,

J A S - F E B 1%9] GUHA ET AL. : B I S B E S Z T L I S O Q U I S O L I S E ALKALOIDS 2s

TABLE 4. Bisbenzglisopuznoline a lka lo ids .

Rz=Rr= R*I= R: '=Me,R ,= Rj= R 4 ' = H , ' R i = R i ' = H ' , . . . . . . . . . . . . . . . , . . . . , ,

R 2 = R 3 = R 5 = R2 '=R31=J Ie ,R4= R4 '=H, ~

R , = H ' , ,Ri'=H,, , . . . . . . . . . . . . , , . . . .

R 2 = R1= R, = R 2 ' = R = R1' = I I e ,R j = H , 1

(6,6 I-Di-0-methyldauri col ine) I Ri = H 1,Ei' = H b , , . . . . . . . . . . . . . , . . .

Rz=R4= I t2!= R 1 ' = R 1 1 = ~ I e , R 3 = R j = H , 1 (6 ' -03Ie t hy1 d auri col ine) I R i = H ,Ri'=H,, . . . , . . , . . , . . . , . . . , . , ,

Rz=R,= R2 l=R4I= ; \ I e ,R~ = R 5 = R3I= H, Ri=H , R i ' = H , . . . . . . . . . . . . . . . . . . . . .

RZ = R 3 = R , = R ? I = R1' =Me) R = R,' = H,

(G-0-Met hyldauricoline) R i = H ! R i = H b . . . . . . . . . .

Config. I l-R,l!-S ' 1. B E R B ~ V C ~ I S E (198)

C1~H,.Osrz:596.2S8638 IIP 190-191; [ a lQ+8 i . (199) 1 DEGR IDITIOS: Metal-ammonia.

(198) SOL-RCES: Berber is avizirensis,

B . iniegerriiiia. B . o3longa.

1-R.1'-R I 2. CU~SPIDALISE 1921 1 Cc;H:,0c~2:G10.3042~8

IIP oil: [CY] -48 (CHCl:). (92) UT- 280. (92) ! ?;AIR 2.43, 2.48 ( 2 s S l l e j ; 3.81

(3 s Ohle): 5.2.5 ( 2 s OH). (9?) ' DEGRIDATIOS: Metal-ammonia. 1200 - _ _

I SOL-RCES: Limocia cirspidafa, L. ob lo jigs.

I C3iH;:0a~z:G24.319938 1 3IP 115; [CY] -139 (MeOK). (18)

IIP 100-103: T c Y ] ~ ? -113 (JIeOH).

1-R,l I-R

(104) UT- 283 (4.0). (103) CD -702 1225is -148 (285). (140) KhrR 2.44. 2.48 12 s S b I e ) : 3.78.

3 80, 3 82 (3 x OlIe) . (202) ;\I.\ss 024 (lI-, 0.11, 206 (100).

13n7 --", DEGRIDATIOS. Metal-ammonia.

Sol-RCES: Jfeiizspertiiiini caiiadeiise, (201 i

Jf. daitrzcirni.

4. D.~URICISOLISE (105)

MP amorohous Dotvder: Talz1 -94.6 C~; I I :~0~~~:610.304288 _ _

iMeOHL). (105) S M R 2.48, 2.52 ( 2 s KIIe) ; 3.59,

3.61, 3.84 (3 I OhIe). 5.44 ( 2 x OH): 6.00-T.14 (11 s arom. H) . (105)

DEGR i ~ . m o s : Met al-ammonia. (105)

SOURCE : -If eiiispernium daitri c u m .

1-R,l'-R 5 , D~CRICOLISE (104) CjeH,oOJ? ~596.288638 AIP aniorDhous oov-der: ra120 -105 , . ~

(JIeOH'). (10i) YAIR 2.49, 2.52 (2 s S l I e ) ; 3.59,

3.62 (2 s OlIe ) : 5.53 13 s OH): 6.03-7.15:111 s aroni. H) . (104)

DEGRADATIOS: Metal-ammonia. 1104)

SOCKCE : Jf enispernzuni daiiricum .

1-R.ll-R 1 6. DAT-RISOLISE 1204) C ~ - H ~ ? O G S Z :010.304288 1 AIP 99-98: [a]2i -114 (JIeOH)

(103)

26 JOURNAL OF N A T U R A L P R O D U C T S

TABLE 4. Continued.

[VOL. 42, KO. 1

R2=R3=Ra=R3'=R4'=hIe,Rj=R2'=H, R,= H;(p,RI'= H, , . . . . .

Rz= R $ = Rj= R2'= Ra' = hle,R4 = R3'=H,

(12-0-Methylespinine) R i=Ri '=H 1 1 . . . . . . . . . . . . . . . . . . . . . . . . . .

R2= R8= R2I= Ra'=Me,Ra= R E = R3'= H Rl = R1' = H ; I \ . , , . . . . . . . . . . . . . . . . . . . .

R2= R3= Rs= R2' = R31 =Me,R4= R,' =H

(Epimer of cuspidaline) Ri= Rj '=H,. . . . . . . . . . . . . . . . . .

Rz= R4= Rs= Rz' = R4I= H,R, = RBI= M e R1 =Hll:!,R1' =H, . , , . , , . . . . . . . . . . .

1-R,l '-R

1-R,l '-S

1-R,l '-S

1-S,l '-R

1-R , 1 '-R

UT 284 (3.95). (103) KMR 2.48, 2.51 ( 2 x Nhle); 3.55,

3.00, 3.80 13 x Ohle); 5.95, 6.02 12 x arom. H) : 6.50-7.20 (9 x arom H) (103)

(203 1 (204)

M. dnlLrlczk7n

MISS 610 (AI-, 0 I ) , 206, 192.

D E G R ~ D L T I O ~ : Metal-ammonia.

SOCRCES: J f e n z s p e r m z ~ n ~ cenadense,

7. N '-DES\IETHTLDA~RICI~E (103)

MP oil (unstable), La]27 -98 Cz-H~206?;2.610 304288

(MeOH) (103) T-T 2x3 ii n, (103'1 ?JhlR2.G -(l x x I h e ) ; 3.60, 3.82

(2 Y OMe), 3.84 ( 2 x OMe): 5.65 12 Y H , lost in DzO); 6.50-7.30 (10 to 11 x arom. H ) . (103)

206, 192. (103) h i s s N o molecular ion peak, 419,

DEGR~DATIOS: Metal-ammonia.

SOURCE: A21enisperm2inz canedense.

8. ESPINIDINE 138)

(103)

C~;H~zO~S2:G10.304288 MP amorphous poFder; [a] +31

S X R 2.44, 2.55 (2 x SAfe); 3.57, 3.79 (2 x Ohle). (38)

Mass 610 (hl-, <0.3), 192 (loo), 177 (26), 163 (metastable). (38)

DEGRADATIOS: Met al-ammonia.

(CHC18). (38)

(38) SOURCE : Berberis luurina.

9. ESPININE 138) C36H4CO6N*:596.288638 RIP 123-125; [a] +25 (CHC13). (38) NMR 2.41, 2.49 (2x SAle); 3.57,

3.77 ( 2 x OMe); 6.02, 6.25 (2 x high field arom. H). (38)

Mass 596 (If+, <l), 192 (loo), 177 (261, 163 (metastable). (38)

DEGR.LD.~TION : hlet al-ammonia. (38)

SOURCE: Berberis luurina.

10. GRISABISE (21) C3jH,z06N.:610.304288 3IP 145-146: [a] -60.2 (CHCl,).

(21

(4.17). (21)

(3 x Oble). (21)

(loo), 175 (15). (21)

UTr 224 (4.25), 237 (4.26), 287

S M R 2.43, 2.48 (2 x KMe); 3.83

M a s s 010 (ML, 4) , 418 (4), 192

DEGRADATIO~X: Metal-ammonia. (21)

SOURCE: A buta grisebachii.

11. LISDOLDHAUISE (94)

J A S - F E B 19791 GUHA ET AL. : B I S B E S Z T L I S O Q U I S O L I S E ALKALOIDS 27

TABLE 4. Coniznited.

Cz,Hj,O,S,:SG8.25;338 JlP 183-186; La]33 7-35 (EtOH)

194 I UT- 205 (4 .651, 220 sh (4 39), 280

S N R CFjCOOH. 3.98 ( 2 'i OMe); 6 79-7.54 (11 x arom. HI (94)

Miks 568 i l l - ) . 178 11001. 194)

(3 91) (94)

R2=R3=l i ? '=P \a '=~ le ,RI=Rj=R4 '=H

(Enantiomer of berbamunine) R i = R l ' = H b . , . . . . . . . . . . . . . .

R2= R 3 = R i = RE= R2'=RJ'= Rq '=ble , Ri=H"i, R i ' = H b . . . . . . . . . . . . . . . . . , . . .

R2=R,=R4=Rj=R3'=hle,RZI=RII=H R i = H b , R l ' = H ' ! . . . . . . . . . . . . . . . . . . . . .

1-S,l'-R

1-R,l '-R

1-s , 1 '-s

R2=R3= R 4 = Rs= Rz'=R31=Me,Rr'=H, R1=Hb,Rl '=H, 1 , , . . . . . . . . . . . . . . . . . . . I (2'-,V-Met hylnort halibrine)

l-S,ll-S

, \ , DEGRADITIOS :I ' i\Ietd-ammonia.

SOURCE: Lindera oldlianiii.

12. MAGSOLISE igrisabutine)

(94)

1205. 21) C ,H ,,b6S2:596.288638 LIP 178-179: [a] -9.G (pyridine). 3IP 192-193 (17): :a' -50 (CHCI,).

n 1 (LlJ

U T - 224 11.24). 239 14.25,. 287 (4.011, 320 sh ( 3 . 2 5 ) . iP1)

3.71 ( 2 s OJle). (21)

(loo), 176 ( G ) . (21)

S h l R hlesSO -ds; 2.32 ( 2 x NMe);

Xiss 596 (AI-, E), 404 (131, 192

DEGR.~DATIOI : Metal-ammonia. SOURCES: d bicta gr i sekachiz , -1lagnol:n .fitscata

12a. O-~~ETHTLD.~TRICISE (69a)

JIP amorphous ponTder; [..Iz0: -78.8 (ethanol). (G9a)

LTT- 283 (4.04 j . (69a) S M R 2.39, 2.42 (2 s S M e ) ; 3.48,

3.52 (2 x OMe), 3.70 (3 x OMe); 2.3-3.5 il4 x a h h . 11): 5.8-7.0

c,sH4606Ne:638.335588

MASS 637 (0.08, hI--H), 623 (0.08), 431 (0.09), 416 (0.15), 206 (100). i f i c ) n ) _ _

SOURCE Coliihrina asintfca.

13. SORTHILIBRISE (150)

MP amorphous powder; [a] +47

UT- 284 (3.10). (150) S l l R 2.46 (1 Y XMe); 3.60, 3.71

lI.%ss G10 (hl-), 206 (loo), 178

D E G R ~ D ~ T I O S . Metal-ammonia.

SOURCE Thalictruni rochebrunianiim.

C,7H4z06~*.610.304288

(CHC1,)- 1150)

(2 x OAle), 3 i 3 (2 Y OMe). (150)

(23). (150)

1150)

14 TH~LIBRISE (150)

bIP amorphous ponder. [a] +110

UT- 284 13 901. (150) M f R 2 45 12 x S M e ) . 3.60 (1 x

CahHdAO Xz 624.319938

(CHC19). (150)

OMe), 3.75 12 x O l l e ) , 3.77 (1 Y

(23). (150)

1 OlTe). (150) , Miss: 621 (ll-)) 206 (loo), 192

28 JOURNAL OF SATTJRAL PRODUCTS [VOL. 42, so. 1

TAEILE 4. Continued.

1 Type Ia

Rz= Ra = Ri = Rc = Rz'= R4'= Rs'=?rIe,

(7-0-Methylthalirugine) R3'=H,RL=H,,R1'=H' ' , . . . . . . . . . . . . .

1-S,l'-S

l-S,l'-S

Type I1

l-S,l'-S

SOURCES: Thalictrunz longistylum, T. rochebrunianunl.

14a. THAL~RACEBINE (144a)

RIP 83-84; [a126 $121' (RIeOH). (144a)

C39H~~Oih-2 :652.314853

UT 278 (3.90). (144a) CD $1030 1238), $111 (289),

-5.1 (310). (144a) NRIR 2.48 (2 x NRle); 3.62 (2 x

ORIe). 3.76, 3.76 (2 x ORIe); 5.87 J (1 x O'CH20); 5.77 (H-8), 6.15 (H-8'); 6.52 (H-5), 6.6-7.2 (7 x arom. H) . (144a)

206 (100). 144a)

(141a) Permanganate in acetone. (144a)

Mass 652 (M+, 0.05), 220 (951,

DEGRADATIOK . Met al-ammonia.

SOURCE : Tiialictrum iiianus.

14b. THALIRUGISE (152a)

?\IP amorDhous solid: ra120 i.92 C~rH~~0;~2:640.314853

(XeOH). (152a) UT 280 (3.81). 1152a)

(282). (152a) KMR 2.43, 2.49 12 x S M e ) ; 3.58,

CD +780 !226), -31 (248), +A4

3.83 (2 x OMe), 3.78 (2 x O l l e ) ;

arom. H ) . 152a)

(35), 132 (83). il52a)

5.50 (1 x OH): 5.73 (H-8'), 6.38 (H-8), 6.47 (H-5), 6.6-7.2 (7 s

M ~ S S 640 (AI', 0.01), 222 (loo), 207

DEGRADATIOX : Rlet al-ammonia.

eT-%O'(3.81). 1152a)

(282). (152a) KMR 2.43, 2.49 12 x S M e ) ; 3.58,

CD +780 !226), -31 (248), +A4

3.83 (2 x OMe), 3.78 (2 x O l l e ) ; 5.50 (1 x OH): 5.73 (H-8'), 6.38 (H-8), 6.47 (H-5), 6.6-7.2 (7 s arom. H ) . 152a)

MASS 640 (AI', 0.01), 222 (loo), 207 (35), 132 (83). il52a)

DEGRADATIOX : Rlet al-ammonia. (152a) Permanganate-acetone (152a)

SOURCE: Thalictrunz rugosztnz.

14c. TH$LIRCGIV?JE (152a)

RIP amorphous solid: [a]20 +lo4 (AZeOH). (152a)

UT' 281 (3.90). il.52a)

(287). (152a) KMR 2.48, 2.50 (2 x NRIe); 3 3 ,

3.61, 3.78, 3.80. 3.83 (5 x ORIe);

arom. H ) . (152a)

(loo), 192 (26). (152,)

(152a)

C39H,,O;Sz:G54.330503

CD $930 (230), -21 (252), $145

5.4 (1 x OH': 5.71 1H-8), 6.11 (H-SI), 6.53 (H-5'), 6.6-7.2 (7 x

Rliss 654 (AI', 0.8), 222 (681, 206

DEGRADATIOS : RIet al-ammonia.

SOURCE: Tlielzctrim rugosztnz.

15. ?\.I.iGSOL.AillISE (206)

JAX-FEB 19791 GUHA ET .4L. : BISBESZTLISOQUISOLISE ALKSLOIDS 29

TABLE 4. Continued.

2l-N-Me t h yl t halis t yline.

5-O-Demethylthalist yline. . . . . , . . . . . . . .

Type I11

l-S,l'-S

1-S,l'-s

C3;H,,Oi?i2 :626.299203 MP lli-118; [a]?* +180 (EtOH).

1206 )

D E G R ~ D ITIOS: lletal-ammonia. (208) Permanganate. (206)

SOURCE: Jlagnolza f u s c a t a .

16. X-DESMETHTLTH.~LISTYLISE (140)

LIP amorphous powder; [a]25 +l5l (MeOH). (140)

UT 252 13.81). (140)

C4aH*sOa~*:682.325418

CD +878 (226), +68.2 (284). (1401 KMR 2.47, 2.50 (2 K KMe): 3.60,

3.63, 3 . 7 (3 x OMe), 3.82 (2 s OlIe) ; 5.90 (OCH,Oj; 5.75, 5.96 (2 x arom. H ) , 6.51-7.10 (7 x

arom. H ) . (140) bliss 682 (XI+, 0.6), 236 (94), 221

(li), 220 (1001, 206 (141, 205 ( 6 ) , 204 ( i) , 192 14). (140)

SOURCES: Thal?ctrum longistylum, T . podocnrpum.

SOURCES: Thalactriim !ongzstylum, T . podocarpirm.

17a. THILIRABISE (14ia)

Alp 131-132: :alz6: +142. il44a) C,cH <:OS,' 5-:683.333243

\ - - - , \ - - - - ,

CD 7969 (220, +G2.6 (2i9). (144a) KMR 2.55 (1 x Kl Ie) ; 3.45, 3.78

(2 x N-ble) : 3.65 i l s OhIe) : 3.78 (3 x 0311~). 5.93 (1 s OCHZO); 5.58 (H-8), 5.82 (H-8')) 6.2-7.4 (7 x arom. H ) . (l44a)

683 OIL, 26). (l44aj

Miss 222 ( 5 i ) , 220 (100). (144a) I\.I-\ss n ITH CHEMICAL IOBIZ~TIOS

DEGRADATIOK: Jletal ammonia.

SOCRCE: Thalicfrum minus.

l i b . T H . I I I R U G I D I S E (152a)

(144a)

30 J o n R x . 4 L OF n ' a T U R A L P R O D U C T S [VOL. 42, NO. 1

TABLE 4. Continued.

OMe OMe

Isomer of norrodiasine

R ~ = R$= R 4 = Rz1=R31=Rql=h3e,Rj=H, R 1 = R I 1 = H , stereochemistry undetermined

Funiferine-2-iV-oxide. . .

1-s, 1 1-S

Type IV

C~sH4sOsSz:670.325418 MP amorphous pom-der: [a]20;

UV 278 (3.82). (152a) CD +985 (230), $72 (280). (152a) NhIR 2.48. 2.51 12 x " e ) : 3.61,

+112 (MeOH). (152a)

3.63, 3 85 (3 x OMe), 3.81 (2 x ' Ol Ie) ; 5.76, 5.79 iH-8, H-8'), 6.6-7.2 (7 x arom. H ) , 5.1 (2 Y OH). (lB2a)

Miss 670 @I+, 1.4), 222 (loo), 221 (3) , 220 (3) , 207 13) , 206 (8), 192 ( 8 ) , 1i8 (2). (152a)

DEGRIDATIOS: Metal-ammonia. (152a) Permanganate-acetone. (152a)

SOURCE: T'haliitrum rugosunz.

18. THALISTYLISE 1140) C4,H4s08N2+ X-:697:348893 M P 160-153 (chloride); CY]*^ +146

UT- 276 (3 .86) , 283 (3.84). (140) CD $1050 (25), +125 (284). (140) NRIR 2.48 (1 x S M e ) : 3.45 (2x

(MeOH). (140)

N-Me): 3.63, 3.77, 3.85 (3x OAfe), 3.80 (2 x 011~); 5.89 (1 x

6.39-7.44 (7 x arom. H). (140) M ~ S S 697 (XI+ 0.8). 236 (100). 220

OCHt0): 5.7'0 (H-8), 5.77 (H-8'),

I , ~I

(88). (140) DEGRADBTIOS: Metal-ammonia.

SOURCES: T'halictrum longis ty lum, (140)

T. podocarpurn.

P 203 (hydrochloride); [ C Y ] +9i (H2O) (hydrochloride). (107)

SOURCE: Nectandra rodiei .

20. FUNIFERIXE (164)

MP 232-234. 168-169: 1-184.3 C~~H420e,N2:622.304288

I . - (CHC13). '(164)

UT 233 sh (4.64), 286 (4.15), 292 sh (4.12). (164)

CD +1214 (241), +308 (274). (164) R-MR 2.36, 2.64 (2 x NMe); 3.39,

3.48, 3.79, 3.87 (4 x OMe); 6.33- 7.25 (9 x arom. H). (164)

(l), 396 (19), 395 (69), 381 (21), 198 (i7), 175 (27), 174 (21). (164)

hfASS 622 ofL, loo), 515 (I) , 431

SOURCES: Tdiacora f u n q e r a , T . dinklagei.

21. FUXIFERIKE AT-OXIDE (165)

;\IP 207-209; [a]25 $44 (MeOH).

UV- 261 (4.75) , 288 (3.95). (165)

Cd~H4z0 iN2 ~638 .2992O3

(165)

J .4S-FEB 19'791 G r H d ET .iL. : B I S B E S Z l - L I S O Q U I S O L I S E ALKALOIDS 31

TABLE 4 , Confznued .

YAIR 2.62 , 3.16 ( 2 x S l l e ) ; 3.27, 1 3.51, 3.81, 3.91 (4 s 011~); 6.30-

R3 = Rd = Rj= R Q ' =Me,Ra ' = H,R, = Me 8: R 2 ' = H or vice versa, R l = R 1 ' = H , I

stereochemistry undetermined ~

R 2 = R 3 = R ~ = R 6 = R 3 ' = 3 1 e , R 2 ' = R ~ ' = H , R, = R l ' = H , stereochemistry undetermined. . . . . , . . . . . . . . . . . . . . . . .

i

R 2 = R 3 = R, = Rs = R2'=Me,Ra' = R, '=H, R 1 = R1'=H, stereochemistry

undetermined

7 .55 (9 Y arom. H). 1165)

( 7 5 ) . GOT 118). 515 (1). 431 (1). h k s s 638 (MA, 321, 622 (loo), 621

\ - , I ~

430 il), 396 (25), 395 (83), 38f (30) , 364 (3) , 349 (2), 198 (721, 175 (241, 174 132). 1165)

DEGR LDATIOA : Permanganate in

SOL RCE' Tzlzacora J imi fera acetone. (165)

2 2 . SORRODIMISE (107)

RIP 282 (hydrochloride); ICY] ~ 7 4

SOURCE: Secta i idra rodzei.

C~;HI~O~K?:G08.288638

(H?O). (107)

23. OCOTISE (106) C3;HicODS2:608 288638 ?\IP 165: [CY!" +40 *2 (CWCl,).

1106) UT- 224 (4.60), 284 (4.04). (106) ORD +127, [@; Y 10-2= $1700.

1106) S M R 2.31 (1 1 S l l e ) : 3.39, 3.55,

3.80, 3.88 (4 s Ol le ) ; 6.10-7.65 (arom. H). (106)

Mass 608 (AI-, G O ) , GO9 (19), 607 ( G O ) , 485 (I) , 448 (l), 430 (2.8), 416 (1). 402 (1)- 382 (42). 381 (72), 36T (47), 198 (36), 191 (loo), 168 (32), 160 (18). (106)

SOVRCE: S c c t a n d r n rodiei .

24. OCOTOSISE (106) C,-H,cOa~;*:G06.2T2988 h i p ise-188; [(y]24 +29i 1 2

(CHC13). (106)

(3.00). (106) CT- 233 (4.55), 282 (4.01), 298 sh

ORD +Ma, 161 x 10-2> 1700. . _ (106)

KMR 2.28 (1 s Nhle); 3.39, 3.50, 3.80. 3 87 (4 s OMe); 6.41-7.72 (arom. H ) . (106)

Mass 606 (11-, 14), 59 (43), 58 (100). (106)

SOL-RCE: S e c t a n d r a rodiei .

. _ (106)

KMR 2.28 (1 s Nhle); 3.39, 3.50, 3.80. 3.87 (4 s OMe); 6.41-7.72 (arom "1 ilnA\

Mass 6 (100). ( lua)

SOL-RCE: S e c t a i

25. PHLEBICIXE (70)

LIP 195; [ C Y ] +182.5 (CHCIQ). (70) UV 292 13.931. 170)

C3jH~aOsSz:608.288638

ORD -1690 (2311, +495 ( 2 5 2 ) ,

CD -660 ( 2 2 5 ) , +695 (246), -110 -206 (272), +352 (297). ( T O )

(260), +257 (285). (70) XMR 2.27, 2.57 (2 I; S h l e i : 3.38,

3.70, 3.80 (3 s Ol le ) : 0 20, 6.28, 6.50, 6.69, 6.73, 6.78 (6 s arom. H ) , 7.08-7.25 (2 T arom. H ) , 7.28 (1 s arom. H ) . (70)

I Rz= R3 = R4 = R5 = Rz ' = R3' =Me,R4' = H , 1 R I = R z ' = H , sterochemistry undetermined (G1-O-Methylphlebicine)

R 2 = R3= Rzl = R3 '= R4'=?rle,R4= R g = H R1= R1 '=H, stereochemistry undetermined

DEGRIDATIOS: Photolysis. (70) SOURCE: Cremastosperma

polyphlebi im.

26. RODIASISE (io, 106) C3sH420cN;z r622.304288

RI= R3= Rz ' = R3 '= R4 '=Me,R4= R s = H, R1= R1' = H 1 1 ' . . . . . . . . . . . . . . . . . .

Rz= R3= R4= Rs '=R3 '= R4'=ble,Rs=H,

(12'-0-Methylliensinine) R1=R1'=H,!l , , . . . . . . . . . . . . . . . . . . . . . . . .

TYPe v

1-R,l I-R

1-R,l'-R

1-R,l'-R

27. TILIAGEINE (209)

MP 270; [a]*: +132.6 (pyridine).

UT 212 (4.83). 231 sh (4.60). 288

C ~ ~ H ~ O O E X ~ :608.288638

(209 ) '

1 (arom. H). (209)

(4.03), 295 s h (3.96).' (209) NhlR 2.34, 2.60 (2 x " l e ) ; 3.41,

3.76, 3.81 (3 x OMe); 6.2bi.18

MASS 608 @I+, loo), 501 ( l ) , 417 (2), 382 (24), 381 (95), 367 (20), 350 ( 5 ) , 335 ( 5 ) , 191 (82), 175 (lo), 174 (16). (209)

SOURCE: Ti l iacora dinklagei.

28. ISOLIENSIKINE (108) C3iH420~N2:610.304288 ' M P oil; +49.3 (MetCO),

[aIz9 -43.3 (CHCI,). (108) UT' 286 (4.04). (108) KMR 2.38, 2.49 (2 x NMe); 3.70

(1 x OMe). 3.76 (2 x OMe): 5.88 (2 x OH) .' 1108) ~

(108) DEGRADATION : Met al-ammonia.

SOURCE: Nelumbo nuci fera .

DEGR~DATIOK : Met al-ammonia.

SOURCE : (210)

Nelum bo nucifera .

JAS-FEB 19i9] GUHA ET -4~. : B I S B E S Z Y L I S O Q C I S O L I K E ALKALOIDS 33

TABLE 4. Cont inued .

R 2 = R 3 = R , ' = R3 l= l I e ,R4=R4l=H,

(2-,\~--JIethgldaphnoline) R i = R i ' = H . . . . . . . . . . . . . .

R 2 - - R 4 = R 2 ' = R4 '=H,R3= R,'=?IIe, R1=R1'=H , . . . . . . . . , . ( 2 '-*Y-Deme t hyldaphnoline )

Type VI

l-R,l'-S

1-R ,ll-S

l-R,l '-

11P oil. [a] -37.8 (CHC1,). 1110) S l I R 2.43, 2 4 i ( 2 x S l l e ) , 3.52,

3.68, 3.71, 3 77 (4 x O X $ , 6.01- 6 98 (11 Y arom. H ) . 1110)

DEGRID LTIOS: Metal-ammonia. (211)

SOCRCE: S e l i i m b o niiczjera.

31. X R o i r o L r s E (thalicrine) (23, 212)

C3RH3,06St:594.272988 MP 175; [CY]" $327 (CHC13). (81) l IP 198-202, [CY]?* +249.5 (pgri-

I . - , dine). ( i ( - i~ UT 208 (4.91), 228 sh (4.69), 285

(3.95). (174) CD +2200 (224), $210 (293). (141) NXlR 2.53, 2.56 ( 2 x S M e ) ; 3.56,

3.78 ( 2 x OlIe) : 6.32-7.45 (10 x arom. H ) . (174)

Mass 594 (AI-, loo), 593 (53), 382 (46), 381 (%), 368 (8), 367 (40), 364 (8), 297 (3), 192 (li), 191.5 118). 191 ( i s ) , 174 (li), 168 (14). (174).

SOLRCES: dbuta sp lendida , Duphnandra aromat ica , D . tenii ipes, Thalzctrum lucidurn, T . fhzinbergiz, Tr ic l i s ia pa tens .

32. S, ~Y'-BIBSOR.LROMOLISE (118)

hIP 206: [CY] $177 il.\-HCl). 1118) UT- 285 (3.88). 1118)

C34Ha:Osr2:566.241688

S M R CDCls-CDaOD: 2.2-4.6 (14H: benzylic I1 and S-CHSj; 3.61, 3.79 (2 x O l l e , : 6.1-7.6 (10 s arom. H ) . (118)

XISS 566 (?.I-). 1118) SOURCE: Pycuurriiena ornntlia.

33 CEPH~RL\OLI\E 1123) C3SH3606S2 592 255338 MP 270 CY]^^ +319 tCHC1,'I. (1231 UT-282 ( 3 90) 1123) X l I R 2.56, 2 62 12 x X l l e ) , 3 65

(1 \ 0 N e i 5 55, 5.57 11 x OCH:O), 6.33-7.49 110 x aroni. H j (123)

lIi*. 592 (?*I-), 485, 401, 380, 3T9, 365, 348. 333. 192, 190, 175, 174

34 JOCRSAL OF SATURAL PRODUCTS [VOL. 42. KO. 1 TABLE 4. Cont inued .

R2 = R, = Rg = R2' = R3'= AIe,R4'= H, R I = H , , R I ' = H , ~ . . . . . . . . . . . . . . . .

R 3 = R,= Rp'= R31 = ble,R2= R4 '=H, R,=Ri '=H . . . . . . . . . . . . . . . . . . . . . . . . (12-0-Met hyldaphnoline)

R, = R, = R4I = H,R = R2 ' = RO ' = Me, R j = R1'=H, ' l . . . . . . . . . . . . . . . . . . . . . . .

1 '-8

l-SJ '-8

1-R,l '-S

1-R , 1 I-S

Miss 606 ()I-), 605, 499, 405, 404, 380, 379, 365, 348, 333, 192, 190 (TS), 174. (203)

DEGRADATIOU: Metal-ammonia. (192)

Miss 606 ()I-), 605, 499, 405, 404, 380, 379, 365, 348, 333, 192, 190 (TS), 174. (203)

(192) DEGRADATION: Metal-ammonia.

SOURCES: Stepiiania cepiiarentiia, s. S O S i i I ? i i .

35. COCLOBIXE (68) C~:H,~OFS2:606.2i2588 MP amorphous: [a120 +123

UI- 230 (5.0); 211 (4.15), 300 sh (3.84). (68)

YAIR 2.53 (1 x K l Ie ) ; 3.20, 3.51: 3.80, 3.91 14 x ORIe): 6.11-7.60

(CHCla). (681

(10 T arom H ) . 168) hliss 606 (AI-, loo), 605 (SO), 591

(E), 575 (lo), 559 (i), 499 (30), 303 (M-, 30) 168)

DEGR IDATION. Metal-ammonia.

SOURCE: Cocculus trzlobiis.

36. CYCLE IPELTINE (faralaotrine)

(68)

i i q ) CaiH~'~0,N2:608.288638 AIP 232-234; [a]*' -106 (CHC13).

179) UT 282 (3.72). (79) XMR 2.47, 2.53 ( 2 x S h I e ) ; 3.29,

3.73, 3.93 (3 x OM?). (75) Miss 608 (11-, 52), 381 (67), 367

(33), 191.5 ( 2 2 ) , 191 (100). (79) SOURCES: Colitbrznafaralaotra,

Cyclea peltnta.

37. D.IPHKAKDRISE (212) C,sH,,O,S~:59~.272988 hlP 270: [a]16 +480 (CHC13). (82) UT 285 13.91). (179) ORD +l l58 (233), '+65 (280),

NRlR 2.50 (1 x S M e ) ; 3.60, 3.75,

M k s s 594 i?.l+). 593. 487. 417. 416.

+463.5 ( 2 5 7 ) . (215)

3.88 (3 x OhIe). (216)

368, 367,'353,'336,'321,'307,'192,'

12n2 184 (+TI, 178, 161 (++), 160. \---,

DEGR-IDATIOX : RIet al-ammonia.

SOTRCE: Daphnandra micrantha.

38. D-IPHSOLISE (trilobamine)

(212)

121 2'1 C1~Hj~0,Nn:580.257338 hlP 195; [all5 $356.6 (HOL4c). (217) UT- 285 (3.92). (179) ORD f961 (234), $99.7 (280),

$331 (295). 1215) NRI

0: R HCOOH; 3.65, 3.83 (2 \ l e ) . 1218)

Miss ;SO &IL), 579, 473, 403, 402, 368, 367, 357 336, 321, 307, 192, 184 (++I, iis, 161 (++I, 160. (203

JAS-FEB 19791 GCHA ET AL, : BISBESZTLISOQUISOLISE ALKALOID^ 35

T.~BLE 4. C o ~ / i ~ i i e d .

R,= I??'= R ; ' = RA'=lIe,R,= RI=H,

(Epimer of sepeerine) R,=H, ,R,'= H

12-0-Met hylhypoepistephanine

Enantiomer c (+)-epistephanine.

R 2 = R,= R 4 = Rpl = R, '= l I e ,RI '= H,

(Epimer of cycleapeltine) R I = R l ' = H . . . . . . . . . . . . . . . .

R 2 = R , = R 4 = R z l = R3'=Me,R, '= H,

(Enantiomer of cycleapeltine) R i = H ,Ri '=H,

I-R , 1 1-S

1-R

1-R ,1 I-€?

DEGR.ID.LTIOS: ?\Ietal-ammonia. /.Qi '1,

l1.i.s~ GO6 ( X I - , loo), GO5 195), 581, 575, 561, 559, 545, 485> 483, 381, 379, 303 (fT), 190, l i 4 , 145. 1128)

DEGR.LD.ITIOS : Uet al-ammonia. (219,

SOURCES: Siepiiatiirl capitotd, S. jnpoiiicn.

41. (- I-EPISTEPHIUISE (21) C 3-H 3,0, S :606.272988 LIP 198-206: [a!20 -210 (CHC1,).

121) Uf--i84 (4.231. (220) SOURCE: diiisocycleri gradidicri.

42. HOJIOhRO\fOLISE (,homo- thalicrinei (711

C,;H,,,O,S,:GO8.~88G38

(158) UT- 284 (3.93). (158) SOURCES: .4 bictn sp lendida , C y i e a

barba.ta, Thnlicir1tni iliicnbergii.

MP 235-2363 [a]" +#25.3 (CHC13).

43. HTPOEPISTEPHASISE (pseitdo- epistephanine) 1221)

C3,H,,06S,:592.257338 ?rIP 256-2973 ral15'j +183.8

c H c i 3 ) . ( i 2 i ) SOURCE: Stcphn?iia jnponir i i .

44. LIX~CL-SISE (92)

l l P 235-237; ;a] 7110 (CHC13). C3-HIo06Sz :608.288638

192) UT-283. (92) S M R 2 47, 2.52 ( 2 Y N l l e ) : 3.33,

3.75, 3.95 (3 s 0Me) . Miss 608 (11-), 383 381, 367, 191 i++, loo), l i s , l f 4 , 168, 141. 192)

(92)

SOURCES: Liniacia cicspidatn, L . ohlonga.

JOURNAL OF KATURAL PRODUCTS [VOL. 42, so . 1

TABLE 4. COntinUed.

R2=R3=R2'=R31=hfe,Ra=R4",

(Enantiomer of aromoline) R1= R1' = H, . , . , . . . . , , . . . . . .

R 2 - - R ~ = R ~ = R ~ I = R ~ ~ = R4I= hle,

(Epimer of obaberine) R1=H,,R1'=H! , , . . . . . . . . . . . . . . . . . . .

l-S,l'-R

1-S,l I-R

1-s, 1 '-s

l-R,ll-S

4 a . hI.\coLmIsE (21a)

MP 179-181: [a120 -320 (CHC13). C36H3i06rlTz:594.272988

(48); 11% (28). b i a j SOCRCE: A b u t a grisebachii.

44b. hfAcoLINE (21a)

MP 255-259 (chloride); [a]20 -60.6

U17 282 (3.92). (2la)

hlass same as macolidme. (21a)

C3iH~*06?;2+'2X-:610.301288

(chloride) (MeOH). (2la)

(278 ) , +110 (296). .(?la) ORD -420 (248), -80 (264), -170

DEGRADATIOS : Metal-ammonia.

SOURCE: Abuts grisebachii.

45. 0-h1ETHYLREPANDIKE (222) C3sHazO6Nz:622.304288 MP 211; [all3 -73 (CHCla), [a]20

UT* 206 (5.11), 233 sh (4.65), 282 (3.81). (215)

-113 (247), -28.9 (260), -166

NhlR 2.55 (2 x Nhfe); 3.05, 3.40, 3.i5, 3.95 (4 I Ohle). (39)

?*lass 622 (hf+), 621, 515, 431, 430, 396, 395, 381, 364, 349, 335, 311

114. (203) DEGR~DATION: Met al-ammonia.

SOURCES: Dmphnendra dzelszi, D .

-108 (0.1 NHCl). (82)

ORD -105 (226), $711 (234)J

(276), -71.6 (289). (215)

(?+I, 198 (++), 175 ( + + ) J

(222)

repandula.

46. OBABERIKE (O-methploxy- acanthine) (223)

C 3zH 4 2 0 6x2 622.304288 MP 139-140; [aI9 $302. (223) ORD 179.1 (2271, 1634 (2461,

C81.1 1289). t135 .5 (29- 2 ) (215) NhlR 2.56, 2.65 (2 \ NMe) 3 19,

3 62, 3.77, 3.88 (4 \ Ohlei. (39) Miss 822 (hI+), 621, 515, 431, 430,

396, 395, 381, 364. 349, 335, 311 ++I, 175 (++I, (-+I, 198 (

174. (203)

(224) DEGR.~D.\TIOS: Metal-ammonia.

SOURCES: Berber is iiiirrino, B . i schonoskyana, T'hn!ic!riciii lztcidztm

J.4N-FEB 19791 GUH.I ET AL. : BISBESZTLISOQUISOLISE ALKALOIDS 37

TABLE 1. Cont inued .

Me N FJ&?+&%

R2= R 3 = R z ' = R 3 ' = R4'=31e,R4=H,

(Epimer of oxyacanthine) RI=H,.P\I'=H I

L-R,l'-S

l-S,l'-S

1-R .1 '-s

47. OBLOSGIMISE (12)

11P 198-200. 142) C3EH430EX2-X-:623 ,3121 13

U T - 281 (3.972. (42) MASS 622, BO{, 577, 564, 550, 501,

411, 396, 395, 381, 220, 206, 198, 175, 174, 58 (100). 142)

SOVRCE :

178. OXOEPISTEPHISISE (12Ga) Cs7H seO;S 2:G20.252253 l I P 224-226: :a]2i 4-27? (CHC1,).

SOURCE : .S/epliunio lierna n d i f o l i a .

Berber i s o bl on go.

(126a)

48. OZT.ICASTHISE (224j Cj;H:rOeS2 r608.288638 RIP 212-214: Tal29 $285.6 ICHCl,). . .

1176) LTT 206 (1.94), 238 sh (5.45), 282

3.G0, 3.;; (3 s Ol le ) . (176) MASS GO8 (AI-), GOT, 501, 117, 416,

396, 395, 381, 361, 349, 335, 304 f + + ) , 198 (++: loo), 192: 175 i++), 1T1. (203)

DEGR.\D.~TJOS: RIet al-ammonia. (224)

SOCRCES: Berber is aquifoliirni, B . j lor ibunda, B . integerrinza, B . ju l ianae , B . lember t i i , B . oblonga, B . fhitnbergii , B . t s c h o n o s k y n a , B . w l g a r i s , Coccitlits laeaba, -1fngnolia comprCssa, -1Iahonia acanthifolia, AI. borealis, AI. for tune i , JI. gr i f i t h i , Jf. leschenaulti i , *If. ninnip i t rens is , JP. s i kk imens i s , Jf. s imons i i , Thal ic t runi l i iciduin, .riantiioriiiza simplicissinin.

49. REP.ISDISE ( 2 2 2 . 225) C,jH,aOsS2:608.288638 RIP 254; [a]" - 101.3 (CHC12.

/ooo\ l L L L l

CV 284 13.83 i . (179) ORD - 1360 (21T), +580 1236 ) ,

-46.4 1258). -239 1279). -136 (292) (215)

SRlR 2 50 ( 2 x S3Ie ) ~ 3 02, 3 38, 3 T3 (3 x OlIer (39)

lI-\qq 608 i l l - ) , 607, 501, 417, 416, 396, 395, 381, 364, 349, 335, 304 (-+), l!8 (+T), 192, 175 ( + + I . l l 4 1203)

50. ~ E P E E R I \ E incotearnine I 1218) C3FH-.0eS2 594 272988 31P 222 +392 iCHCl 1 (218) CT- 284 (3 791 (182)

38 JOURSAL OF SATURAL PRODUCTS

TABLE 4. Continued.

[VOL. 42, so . 1

R = R 3 = R 4 = R l l = R8'=hle,R4'=H,

(Enantiomer of homoaromoline) Ri=Ri '=H,

R2= R 4 = R E = Rz '= R 3 ' = R4'=hle,

(50-DemPthyl thalrugosnminine) R3= H,RI=H,,Ri'= H 1 1 ; . . . . . . . .

1-S,l I-R

Type VI1

1-SJI-s

MASS 594 (M+), 593, 487, 417, 416, 382, 381, 367, 350, 335, 321, 297 it+). 191 1++). 178, 168 (++ j; EO. (203) '

DEGRADATIOS: Metal-ammonia. (218)

SOURCE: A'ectandra rodiei .

51. STEBISIMINE 11281 C36H340s~;2:590.241688 LlP 233-235. (128) UT- 238 (4.71), 279 (4.38). (128) S M R 3.25, 3.88, 3.90, 3.96 (4 x

OMe); 5.91 (1 x ai-om. H) , 6.2- 7.2 (8 x arom. H) . (128)

PyI~ss 590 (M-, loo), 575, 559, 370, 295 (++, 13), 221, 206 (171, 192, 175 and a low abundant peak a t hlL $14. 1128, 203)

DEGRID~TIOS: Metal-ammonia. (128)

SOURCES: A n i s o c y l e a gradidieri , S t ephan ie japon ica , Tr i c l i s ia gil leti i .

52. THALRCGOSAVISE (153)

MP 122-125; [..]so +280 (MeOH). CiiH4oOfiN2:608.288638

11.52) U<--%2 (3.91). (153) CD f140 (220), +165 (225), +6.1

(274), 7.0 (280), 9.12 (293). (153) NhlR 2.51, 2.55 (2 x Nhle); 3.60,

3.78, 3.88 (3 s OMe); 6.3-7.5 (10 x arom. H). (153)

Mass 608 (M-, 5 l ) , 382 (23), 381 (74), 367 (29), 206 (931, 205 (28), 192 (SO), 191 (loo), 190 (39), 176 123). 175 1281. 174 (39). 168 (28); 149 (90): (153)

(153) DEGRID~TTOS: Metal-ammonia.

SOCRCE: Thakc t r z im riigoszim.

52a. THALIGOSISE (152a)

RIP 143-145; ral -109 (RIeOH). C3iH1?0;~2.638.299203

. _ (152a)

US- 282 13.86). 1152a) Cil ClA7 12253. -79.8 1240). _ _

-12-(272), +32 (287): (15ia) X l I R 2.52, 2.56 (2 x S M e ) ; 3.08,

3.39, 3.78, 3.95 (4 x Ohle): 6.38

arom. H ) ; 4 .7 (1 x OH). (132a) RLiss 638 (AI+, 89), 637 (2i) . 023

(H-8), 6.46 (H-5), 6.6-7.4 (7 x

(a), 412 (25). i l l (92), 222 (14), 206 (++, loo), 192 (30). (152a)

D E G R ~ D ITIOS: Metal-ammonia. (152,)

SOCRCE : T h a lict r 11 nz r ugosirni .

JAS-FEB 19791 GUHA ET AL. : BISBESZTLISOQ~ISOLISE ALKALOIDS 39

TABLE 4. Conhiizied.

Rz=R3= R,= R:= R1s= Rs'=?\Ie,R' '= H,

(12'-O-Derneth-l thalrugosaminine) R i = H k , R i ' = H

Rz= R,= R j = R P f = R3' = R,' =Me,Rs= H,

(12I-O-Met hylthalisopidine) R1 =H,,R1'= H! . . . . . . . . . . . . . . . . . . . .

l-S,l'-S

1-SJ1-S

1-SJI-s

1-s , 1 1-s

52b. THALIGOSISISE (152a1

IIP 233-234.5: lajnl -58.5 QIeOH). C3sH,?O;S,:638.299203

il52ai UT- 282 (3.90). (l52a)

- 130 ( 2 7 5 ) . il52a) SAIR 2.51 , 2.56 ( 2 I S M e ) , 3 04,

3.40, 3 80, 3.84 (4 x O l Ie ) , 6 36 (H-8), 6.47 (H-3 , 6.5-7.5 [i 'i arom. H ) , -5 0 (1 x O H ) . (152a)

MASS 638 (AI-, loo), 426 (E), 425 (3_7), i l l (34)) 236 ( 2 ) , 213 (ff, 94), 192 (311, 191 (6), 190 (9). (152a)

CD ~ 1 0 0 0 (230), -480 (2421,

SOTRCE: Thalzctriim riigoszim.

Ut- 282'13.901. 1152a) CD ~ 1 0 0 0 (230), -480 (2421, - 130 ( 2 7 5 ) . il52a)

SAIR 2.51 , 2.56 ( 2 I S M e ) , 3 04, 3.40, 3 80, 3.84 (4 x O l Ie ) , 6 36 iH-81. 6.47 iH-5). 6.5-7.5 i i 'i arom. H) ; -5.0 (1 x O H ) . (152a)

MASS 638 (AI-, loo), 426 (E), 425 (3_7), i l l (34)) 236 ( 2 ) , 213 (ff, 94), 192 (311, 191 (6), 190 (9). (152a)

SOTRCE: Thalzctriim riigoszim.

IL'hIR 2.44, 2.19 (2 x S l I e ) , 2.96, 3.30, 3.70 (3 I OMe) . 6.4-7.2 (9 x arom. H ) . (139)

SOURCE: Thnlzctrum isopyroides .

!51. T H ~ L I S O P I ~ E 1139. 9) C33H420;X2:638.299203' RIP 151-153; [a]2o -104.9

UT- 284 (3.65). (227) (hIeZCO), -71.02 (CHC1,). (22

ORD -250 (213). -100 (265).

17

-225 (280). (228) S M R 2.13. 2.18 12 Y Xhle) 3.00.

3.29,-3.i0, 3.86'74 s OMe): 5.10 (1 'i OH): 6.31, 6.38, 6.57, 6 .77, 6.85, 7.06 (9 s arom. H ) . (139)

Mass 638 01-, 11). 412 (89), 221 (18), 206 (+'+, loo), 183'(17), 174 1181, 173 (29), 142 (891, 90 89 (20). (139)

(197) DEGR.ID.ITIOS : Met al-ammonia.

SOCRCE : Thalict r i m i s o p y o i d e s .

5 5 . TH.~LRTGOS.UIISIKE' 10- met 11, It hallsopine) (1481

(148 I

C ~ Q H I ; O - S ~ 652 314853 MP 103-109, ia]'. -90 4 (MeOHi

UT- 205 (4.891, 227 sh (1.51), 282 (3.94). (148)

CD '812 ( 2 2 8 ) : -534 (242), -85.4 (2721, 122 .5 (2881, -5.9 (2%). (154)

S M R 2.32, 2.57 1 2 s S h I e ) : 3.08, 3.41. 3.80. 3.63. 3.97 ( 5 s OMer: 6.10-7 20 19 x arom H ) . (1541

11 \'.$ G 5 2 IJI-. 49 I . 051 133 I , 426 1191, 425 (59). 411 (221, 409 1191,

'The name 0-methylthalisopine predates the name thalrugosamininr. Still the later name is retained because U-niethylthalisopine n-as not isolated, but %-as detected b:- TLC rrf the mother liquor of the plant extract remaining after separation of rhalisopidine and thalisopine (139).

40 JOURNAL OF X A T C R A L P R O D U C T S

TABLE 4. Continued.

[VOL. 42, xo. 1

R 2 = R 3 = R z ' = R3I=Me,R4= R,= H, R1 = H,,R1'= HI ' . . . . . . . . . . . . .

R2=R3=R,=R2'=R3'=Me,Rs=H, R1= R, '= H'l , , , . . . . . . . . . . . . . . .

R?= Rs= R,= Rt'= R,l=hIe ,R,=H,

[ ( j- )-Fangchinoline] I R1= Ri '=H

l-S,l'-S

1-R,l '-S

214 (27), 213 (loo), 212 (16), 206 (11), 205 (31), 198 (21), 192 ( 7 ) , 191 (6), 190 (16), 189 (6), 176 (14), 174 (38). (154)

DEGR ~ D A T I O S : Met al-ammonia. (148) Permanganate in acetone. (148)

SOURCES: Thalictrum isopyroides: T . recolictum, T . rugosirm.

56. z4THEROSPERJIOLISE (229)

MP 183-188; [a]'' +202 (CHCI,). C36H3,06r\'2:594.2i2988

-- ( 2 0

UT- 284 (3.97). (27) ORD 11520 (233), $60 (204),

1314 1290). 127) KMR 2.62 (2 x NRle); 3.30, 3.7G

12 x ORlp). 127) - _.-_

~ i s s 594 (>I-,-&), 593 (591, 471 (0.8), 463 (8), 402 (6.5), 367 (45), 305 B . 5 ) and 382, 381. 350, 335, 321, 192, 191 (++), 174, 168 (++I. (203, 229)

SOURCE: Atherospernia moscha tum.

57. BERB-WISE (berbenine) (28)

l i p 156: T ~ l 3 ~ +109.7. (31) C31H4006N2:608.288638

UV 284'(3.?9).. (230) ORD $301 (240), +130 (2501,

-78.6 (261), -130 (271): 4-59.9 (294). (215)

NMR 2.25, 2.53 ( 2 x NMe); 3.08, 3.54, 3.70 (3 x OMe); 5.95 (C8'- H). (230)

MASS 608 (?VI', 79), 607 (501, 485 (2), 417 ( i ) , 395 (68), 381 (341, 198 (++, 100). (230)

DEGRADATIOS : Met al-ammona. (28)

SOURCES: Atherospernia moscha tum, Berber is an iurens is , B . aquifoliz~m, B . asiaticn, B . f lor ibunda, B . ju l ianae , B . kawakami i , B . lani- ber t i i , B . lycilLm, B . mingetsens is , B . morrisonensis, B . pe l io lar i s , B . suasey i , B . thunbergi i , B . iinctoria, B . uulgaris, B . zebiliana, Cyclia barbata, Mahonin nquifoliunt, ,M.forticnei, d l . gr i f i th i , 119. japo- n ica , M . loniarii folia, -14. nior- r i sonens is , -19. ph i l ipp inens i s , Pycnarrhena australinna, P . nianil- l ens i s , S t ephan ie cepharaniha, S . sasak i i , Tha l i c t rum foetidztm, T . pedicnculatum.

58. CYCLE.\DRISE (79)

AZP 160-162; [aI25 0 (CHCl?). (79) UT- 282 (3.81). (79)

Cz;HaoO,S2 r608.288638

JAS-FEB 19791 GCHA ET rlL. : BISBENZTLISOQUISOLISE .4LKALOIDS 41

TABLE 4. Continued.

I

1

~ 191 (it. 100). 179)

S M R 2.26, 2.43 (2 s S M e ) ; 3.73 (1 x OMe), 3.88 (2 x OMe). (79)

Mass 608 (AI+, 64), 417 (11), 381 (80), 367 ( 3 2 ) , 191.5 (++, 2 5 ) ,

R 2 = R3= R 4 = R j = R;' =Me,Rz'= H, Ri=H,,R:'H , . . . .

R = R = R = H J R 2 1 = R31 = R = X e , Ri=Ri '=H, . . . . . . . . . (Enantiomer of 2-N-Sorobamegine)

R = R, = R = R z l = R z ' =?.le , R q = H,

(12-0-Met hylat herospermoline j Ri =H,,RI'=H

l-S,ll-S

1-S , 1 '-s

I-S,l '-R

l-S,l~-S

1-R, 1 '-8

] SOL-RCES: 'Cyclea barbata, C. pel tata.

\ - --, \ . - , klIG-5.37 (1 s SMe); 3.30 (1 x

ONE B- 1 s S + l I e ) , 3.54 (1 s S-Me): 3.38, 3 .72 , 3.94 (3 s OhIei : 4.5 liirCH-ST): 6.0-7.4

1 110 s arom. H). 1 i9 )

1 SOURCE: CycIea pel toto.

60. CYCLE ISORISE (79)

PIIP 1iO-172, 7308 ICHC13) C3;H,,O,N2:008.288638

f i 5 I U T - 282 (4.01). 179) S M R 2.33 (1 Y XJIe): 3.22, 3.33,

3.70, 3.88 (4 s OhIe); 8.9-7.4 (10 x arom. 13). (75)

Miss 608 (11-, 5 5 ) , 431 1181, 381 (80), 191 (100). (79)

SOURCE: Cyclea peltata.

60a. T-O-DEJIETHYLPEIS.~~IISE

C3jHj60hS2:580.25i338 1IP 205-206; ~ a ] 2 0 -86 (IZXeOH).

121a)

W a ) U T - 284 (3.95). (21a)

+lo0 ( 2 7 6 ) , -60 (296). (21a) A1 iss 580 (ML, 64 I , 389 ( 5 ) , 388 (2),

368 (31 ;, 367 (loo), 353 ( - I O ' , 192 121), 174 (19). (21a)

POURCE: il biiia przsebachii .

ORD -650 (242), +110 1253),

61. FASGCHISOLISE (231) C1-H,,O~S,:608.288638 UP 237, [ajl8 +250 (CHC13). (13) U T - 236 sh (4.51), 282 (4.01). (171) S J I R 2 33, 2 59 (2 Y Nhle ) , 3.55,

3.77, 3 93 13 Y 0Me) . 6.06-7.23 (10 s arom. HI. 1171) Mass 608 i l l - ) , 607, 471, 417, 416,

382, 381, 367, 350j 335, 321, 192, 191 (++), l i 4 , 168 it+). (203)

DEGRAD.\TIOS : Met al-ammonia. 1231)

SOURCES: Cyclea pe l ta ia , Dapiiniindra species Dt-7, Si e piinn i n h e r n ii nd $0 1 io, S . t e i m n d r a , Triclisia siibcordata

62. ISOTETR.LSDRISE 10- methylherhamine). 1232)

C ~ S H ~ ~ O R S ? 1022.304288

42 JOURNAL O F XBTURSL PRODUCTS [VOL. 42, so. 1

TABLE 4. Contznued.

MP 180-182; [aj6 +l5 l (CHC13). id?)

Rn=R3=R2'=R3'=Me,R4=Rj=H,

(Enantiomer of atherospermoline) R1= H I l ,Ri'=H,

R2=R3= R E = Rzl= R3'=1le,Rp= H,

(Enantiomer of fangchinoline) R ~ = H , R I 1'=H,.

Isomorph of fangchinoline. .

Isomorph of (+)-tetrandrine..

1-R,l'-R

1-R ,l'-R

V?-iOG 14.97), 238 sh (4.38), 282 (3.85). (21.5)

ORD +122.6 1235). -69.4 1251). -40.9 (258); -131 (274),'+1$1 1290). (215)

NRlR 2.28, 2.60 (2 x NMe); 3.18, 3.63, 3.78, 3.95 (4 x OhIe). (39)

?\Iass 622 (MA), 621, 485, 431, 430, 396, 395, 381, 364, 349, 198 (++), 190, 175 (++), 174. (203)

DEGRAD.ITIOS: hlet al-ammonia. (232)

SOURCES: A therosperma moschatum, Berber is kawakami i , B . minget- sens is , B . morr isonens is , B . thunbergii , Cyclea barbata, Laure l ia semperv irens , Mahonia japonica , hl. lomari i fo l ia , hl. morr isonens is , M . p h i l i p p i n e n s i s , Pycnarrhena australiana, P . mani l lens is , S tephania cepha- rantha, Tlialictrum f o e t i d u m , T i l iacora . fun i fera , Tr ic l i s ia gil leti i .

63. KRUROT-IKE (23) C36H3sO6N1:594.272988 IIP 182-183; [a] -180 (CHC13).

(2.1 1 Uf7-%5 (3.82). (23) S M R CDC13-Me2SO; 2.28, 2.58

(2 x NMe); 3.30, 3.73 (2 x OMe); 5.97 (1 x H ) ; 6.28-6.75 (arom. H) , 7.11 (2 x H ) ; 7.32 (2 x H). (23)

hiass 594 (hI+, 69), 593 (441, 487 (<l) , 403 (14), 381 (loo), 192 (is), 191 (95), 190 (24), 174 (32), 168 (25). (23)

DEGRADATION : Met al-ammonia. (23)

SOURCE: d buta splendida.

UT 281. (92) KhIR 2.33, 2.60 (2 x Tu'Rle), 3.33,

SOURCES: Cprlea bnrbata, Lzmacza 3.78, 3.92 (3 s OMe). (92)

curpzdnta, L. ohlonga.

65. RIEKISIDISE (125) C 3:H4rOi;S2 :608.288638 MP 176: [a]23 + 2 G O . (133) SOURCE: .Siephnnza tetrandra.

GB. ~ IELISIKE (126)

RIP 152: +290. (133) CseHizOsSz:622.301288

SOURCE: . Step~ianzn tetrnndra

J A S - F E B 1 9 i 9 ] GCHA E T AL. : B I S B E S Z T L I S O Q C I S O L I S E ALKALOIDS 43 TABLE 4. Conianiied.

R = H , R'= M e o r v c e versa

R2' = RS = R4 = R Q 1 = lie, R, = R5 = H, Ri=Ri '=Hi

1-R, 1 1-s

l-S,l'-R

l-S,l'-S

l-R,l'-S

l-p\.l'-S

66a. 2-S'-~IETHTLBERBI1lIhE (42a) CQ.H~?OFSZ 623.312113 Data not available t o the reviem-er SOCRCE: Berbev ts oblongu.

PEISiMISE (21a) C3e?;3sO~S2:59A.272988 MP 187-190: [.Iz0 -259 (CHCI,).

121a1 L-1- 281 13.90). (21a) ORD -660 (236). $50 (254), i l l 0

S11R 2.28. 2.50 12 x Xhle). 3.75. (278), -55 (291). (21a)

3.85 ( 2 x Ohle), 6.06, 6.iO ( 2 x' arom. H i . 121a1

I\l.~ss 594 (11'; i l ) , 471 (l), 403 (8), 402 ( G ) , 382 (29), 381 (loo), 367 (AS), 192 (91), 191 (loo), 174 (59), 168 125). 121a)

SOCRCE: d buta gr isebachi i .

67. ; I~OSOJ~ETH~LTETR~NI)RI- XIUV (75 )

C rqH,eOFS,'-2S-:638 ,335588 LIP 208. +51.5 (MeOH). (75 ) KYIR 2 50, 2.78 ( 2 s S l l e ) , 3.18,

3.41, 3 71, 3.90 14 x 0 1 I e i . 5.9- 7 . 3 (arom. H) . (75)

MISS 622, 621, 620, 607, 591, 485, 483, 431, 130, 416, 396, 395, 393, 381, 379, 3W. 3\50, 319, 335, 311, 206, 205, 204, 198.5, 198, 192, 191, 190, 175 5, 175, 174, 160, 14Gj 145. (75)

SOI-RCE: Cyclea hiirbiita.

C36H-,0BS2:594.272988 MP 166-168: [CY] +I17 (CHCI,).

Ui-282 13.831. (116, X l I R 2.62 tl -, SAIe) , 3.12, 3.62,

68. 2 - A ~ - ~ O R B E R B . I J l I ? E (1 16)

1116)

3.78 13 s 0 3 k i . 1116) X I ' S 594 (ll-, 3 5 i , 382 (1001, 192

B O , , 191 f 8 5 ~ , I74 136). 1116)

'CY]" -116 (0.lS HC1). (118) UT- 283 (3.84). (118) S l l R CDCIj-CD,OD: 2.52 i l s

S N e i : 3.73, 3.85 ( 2 s O J h : 2.3-4.2 (14 s 11: benzylic CH and S-Me I : 6.O-i.5 (10 1 amni . H I . 1116, 11%

JOURXAL OF NATURAL PRODCCTS [VOL. 12, so. 1 44 TABLE 4. Continued.

I

R3= R a = R5= R Z 1 = R3 '=Me,Rz=H, Ki=H,,Ri'=H I . . . . . . . . . . .

R 2 = R3 = Rzl = R,' =1le,Rd = R5 = H,

(Epimer of atherospermoline) R1= Ri ' = H 1 1 8 , , , , , . , , . . . . . . . . . . .

R3= R 4 = RZ1= Ra'=ble,R2= R j = H, Ri=RI '=H, . . . . . . . . . . . . . . .

R 2 = R 3 = R,= R21= R3 '= l I e ,R5=H,

(Enantiomer of pycnamine) Ri=H, ,Ri '=H I

1-s , 1 1-S

1-R ,1 '-S

l-S,l 'R

Mass 580 (M-, 25), 368 (25), 367 (SO), 353 (15), 192 (15j, 191 ('io), 184 (loo), 174 (40), 161 (30). 1116)

SOURCES: Pgcnarrhena australiana, P . ozantha.

io. 2-XORTETRASDRIKE (106) C-;H?aOe,N2:608.288638 UP 222-226; $33512

(CHCI,). (106) TJT- 22 i (4.53), 282 (3.88). (106) ORD a: +139, [+] XI lo-*: $1410.

i~nfi'i d R ' 2 . 6 2 (1 x NRIej, 3.22, 3.39,

Rliss 608 (11-, 54), 607 (47), 501 3.i6, 3 94 (4 x OXe) . (106)

(l), 471 (l), 382 (441, 381 (1001, 367 (14), 191 (+T, 89), 168 (26), 174 (21) (106)

DEGRAD ATIOS' Metal-ammonia. (106)

SOCRCE Sec fa i id ra rodiei .

71. OBAUEGIRE (stepholinej (129) Cz6H 3606K2:594 .272988 M P l i l - l i3 : rali9 +273 (CHC1,).

I . ~

1129)

l-S,l'-S

I . , ,, DEGRADATION: hleta1:immonia.

(129) SOURCES: Berberis tschonoskyana,

S tephania japonica , Thalictruni lucidurn, T . rugosum, Xanthorhiza s impl ic i ss ima.

71a. PEINAMIKE (21bj

M P 1iO-171; [a120 -109 (CHC13).

UT- 282 (3.90). (21b) ORD -30 (296), +250 (2i5), $160

C,sH34ObNz:594.272988

(21b)

(263), +440 (2501, -690 (237). (21b)

NRlR 2.55 (1 x X l l e ) ; 3.06, 3.55, 3.68 13 x OAIe): 6.0, 6.22 ( 2 x arom. H ) . (21bj

XASS 594 (\I-, 22), 471 (I) , 403 (l), 402 (l) , 382 (26j, 381 (loo), 367 (20), 192 (18), 191.5 (4). 191 (28), 174 (30), 168 (15). (21b),

SOURCE: d birta p s e b a c h z .

7 2 . PEKDULISE (233) CaiH,,OsNz :608.288638 LIP 192-194; [a] +265 (CHC13).

(66) UT';284 (3.84). (233) X3lR 2.32, 2.62 (2 x NRle); 3.21

( 2 XI OMe), 3.i5 (1 x Ol l e ) ; 2.88,

JXS-FEE 19791 GUHA ET AL. : BISBESZILISOQUISOLISE ALKALOIDS 45

TABLE 4. Continued.

x- 3 _"

' OMe 0 ' R,= R,= R a = R j = R2 '= R3' =Me,

(Enantiomer of tetrandrine) R I = H ,RI '=H,

R, = R, = R 4 = R, ' = R ' = Me, R a = H,

(Epimer of berbamine) Ri = H , FtI ' = H b , : . . . . . . . . . . . . . . .

1-R,l'-R

1-R.1'-R

3.42, 3.90 (8 ring methylene, 2 ring methine and 4 benzylic pro- tons respectively); 6.05, 6.79 (2 s arom. H) , 6 20-7.40 (10 s arom. H) . (66)

Miss 608 (ll-j, 607, 416, 396, 395, 381, 364, 319, 198 (++I, 198.5 (++)1 175.5 (Sf) , 175, 174. (66)

SOURCE: Coccitlits pendu lus .

7 3 . PH.XE.ISTHARISE (113) C3iHd60sS?-- 2X-:616.257338 LIP 124-130 (picrate), 180-184

(perchlorate). (113) U T - (113) DEGRIDATIOX: Metal-ammonia.

1113) SOURCE : Phaeanthzt s e bract eola t u s .

,.-*,

(3 91). (215)

-87 (268), -257 (290). (215) S M R 2.30. 2.60 (2 x XMe); 3.20,

3 .32 , 3 . 7 2 , 3.87 (4 s OhIe); 3.08 (ring methylene). (216)

Miss 622 (11-), 621, 485, 431, 430, 396, 395, 381, 364, 349, 198 ( + + I , 192, 175 (++), 174. 1203)

ORD -810 (2281, -1350 (236)j

DEGR.XD.~TIOX: Metal-ammonia. (178)

SOCRCES : Piiaeantiiiis e b m c t e o l a t u s , Pyc i iu r rhem m u ~ i z l l ~ ~ ~ s z ~ , TricIzszu p a ' e n s .

Gyroca rpits alii erz can u s ,

75. PTCXIJIISE 1234. 235 I C3;H,rO~N2:608.288638 JIP 186-187: [ a 1 2 5 -283 (CHC131

(1171 UT--'%9 sh (4.59), 282 (3.991, 292

13.88). 1171) ORD -406.5 f227), -609 ( 2 3 5 ) ,

-83.1 12671, -190 (290). (215) S U R 2.32? 2.60 12 s Tl Ie ) : 3.18,

3.22, 3.71 (3 s OJIe): 6.01-7.24 110 s aroni. H ) . 1171)

Xiss 608 (11-1, 607, 485, 417, 416, 390, 395, 381, 364, 349, 336, 304 i++), 198 (+- I> 192, 175 j - + j , 174. (2031

L)EGR~D.\TIOS: Metal-animoni.. 1234

SOTRCES : G jrorii rpit s riwi erictiii Its, Py i i i r r l i e i iu i i ioii i l l t i isisj Triclisiii p n t ~ i i s .

l-S,l'-S 76. ~--!-TEIRISDRISE 12321 C-,H110~Sr:A22.304"88 1IP 218: .a:?] +241,4 fCHCI.,I.

k174)

46 JOURSAL OF SATURAL PRODUCTS [VOL. 42, so. 1

TABLE 4. Coniinzied.

R z = R,= R?= RE= R2'= Rg'=hIe, R i = R i ' = H . . . . . . . . .

Tetrandrine-.\'-2 '-oxide

Rz = R = R J = R = R g = Me,R = H,

(Epimer of fangchinoline) R i = R i ' = H , I , . . . . . . . . . . . . . . . . . . .

' UT214 (1.78), 283 (3.91). (174) 230 (1.40), 282 (3.89). (105)

ORD +1490 (235), $138 (2?2), $249 (289). (215)

S l I R 2.29, 2.58 ( 2 x S M e ) : 3.15, 3.31, 3.G9, 3.87 (4 x Ohre). 5.91- 7.35 110 -i arom. H) . (174)

X~SS 622 (?\I+, %), 621 (41), .515 ( l ) , 501 (I) , 455 ( 2 1 , 448 (l), 430 1 G ) , 395 119). 395 1 G 5 ) , 381 133)

I I

i@'(+T', IOO), 1ii (++, 39:. (106)

DEGRIDATIOS : IIetal-ammonia. ( 2 3 2 )

SOURCES: Cocczilzis saraientosus, Cyclea barbaia, C . bzirinunni, C . pe l tn ia , Siepiianin lierna+id$olia, S. te!randra, Triclisia sitbcordata.

-- i t . (+)-TETR~NDRISE (125) Cj<H4206S2:622 301258 1IP 257-253: [a] 0. (1251 SOCRCES: Cyclea barbata, C.

78. TETR.ANDRI>E ~ 0 ~ 0 - X - 2 ' -

p e l iaia , Stepha m a i iernandzfo Iia .

OYIDE (72) C3eH420iN2. 638.299203 M P 185-190: [a]23 +198 (CHClg).

172 I N k R 2.31 (1 x KRIe): 3.25, 3.35,

3.71, 3.92 (4 x OMe); 3.54 (1 x >le S-0). (72)

?\ISM €138 @I+, l5) , 622 ( G i ) , GO7 (22), 591 (12), 431 (7.5), 430 ( G ) , 396 (IG), 395 ( 5 5 ) , 382 (8), 381 (30), 3 i 9 (ll), 200 (6) , 204 ( i ) , 198.5 122)) 198 (loo), 197.5 (3), 175.5 110). 1i5 125). ( 7 2 )

SO~RCE: Cyc l ia bar'baia.

79. THALRUGOSISE (thaligine, isofangchinoline) (147, 152)

RIP 153, :.Iz5 $87 (MeOH).

UI- 282 13.94). (147) ORD $79.G (240), $4.9 (270),

$10.6 (288), +O.G (310). (117) M I R 2.31, 2.53 (2 x NRIe); around

-CH-): 3.76. 3.92. 3.94 13 x

C3;H1,06~2:608.288638

(147)

2.90 ( G x -CH,-); 3.59, 3.62 12 s

1-R ,1 I-S

(152)

licirztin lzictdzini, T . polgganum, T . rugoszrm, T?lzacora fimjeera.

SOURCES: Cyclea barbatn , Tha-

J A S - F E B 19i9] GUHA E T AL. : B I S B E S Z T L I S 0 Q ~ I S O L I S E ALKALOIDb A i

T ~ B L E 4. Coii+iiii,ed. I

R,=R,= Ft4=Rj= Rb= R?'=R31=?.le, ~

R1= H, ,€il l = H , . , , . , , . . . , . , . , , 1-6,. 1 '-S

3.88 (3 x O3Ie I : 6.28-7.39 110 s arom. H I . t l66nI

Silfi-z.G?-il x 'S<Ie) : 3.28, 3.34, 3.75, 3.92 (4 z OlIe ) ; 5.57-7.42 (9 x ai-om. Hi. (146)

31.m 624 (lIL> 1911, 623 (13j, 398 ( l l ) , 208 (9): 199 (211, 192 (loo),

S O U R ~ E : T h n l i c i r u m podocarpzciiz. 191 13), 176 (4). (146)

81. HERSISDEZISE (thalicsimine) f l S A 1

C31H,,O-S?:652.314853

L-1- 209 14.99), 283 (3.90). (138) ORD 71357 (229), +1490 (2352,

CD -703 (245), -166 (2731,

S l I R 2.30, 2.63 (2 s S 3 l e ) : 3.24, 3.34, 3 . i 9 , 3.83, 3.91 ( 5 s O1Ie); 6.02-7.50 (arom. H) . 1138)

Misq 652 (ll-), 651, 461, 426, 425, 411, 394, 379, 365. 213 (++, 1001, 192, 190 (++), 1i4. 1196, 203)

DEGRLDATIOS: Met al-ammonia.

MP 192-193: r a l 2 o +EO (CHci3) . (138)

-18.8 (2T5,1 $235 (292). (213)

+199 1290). (236)

(196) SOURCES: Tiinlictrzci?i feizdleri ,

T . liernnnde:ii, T . podocarpunr, T . roche b y i i niu ii i i m , T . sin1 p i e r .

82. I ~ O T H I L I D E Z I ~ E (146)

l l P 136-138. [a: - i0 (1leOH) Cj,Hd,O-S2 638 299203

(1 46 1 UT-282 13.99). (146) CD -638 (230), +370 (2471,

-217 (285) . (146)

48 JOURR-at OF N A 4 T U R A L PRODUCTS

TABLE 4. Continued.

[VOL. 42, NO. 1

R3= R4= R5 = Rs = R2I= R3I= h l e , R ~ = H ,

(2-A~-Demethylhernandezine) R 1 = H b , R l 1 = H 1 , . . . . . . . . . . . , . . . . . . . .

OH

1:l Mixture of two conformers of 50-methylthalsimidine

l-S,ll-S

1-S,l'-S

1-s

NhlR 2.23, 2.54 (2 x Xhle) : 3.18, 3.62, 3.75, 3.88 (4 x OhIe): 4.85 (phenolic H ) : 5.99-7.33 (9 x arom. H ) . (146)

(23), 411 (go), 397 (38), 222 (11), 206 1861. 192 11001. 1146)

Mass 638 (&I+, 47), 637 (18), 412

DEGR.~D.&Iox : 'Met al-ammonia. (146) SOURCE: Thalicf r i m podoca r p u m .

83. TH~LIDEZISE (135) C3sHJ20;S2:638.299203 h lP 158-159 [ C Y ] +235 (CHC1,).

(135) CT- 283 (4.02). (132)

$382 (288). (146) S h l R 2.33, 2.64 12 x KMe); 3.27,

3.37, 3.78, 3.92 (4 x OMe); 6.02, 6.12-7.5 (arom. H). (135)

hlass 638 (hl+), 411, 192. (135) DEGRADATIOK: Metal-ammonia.

(135, 146) SouncEs: Thalictruni fendler i , T .

mznus, T . podocarpum, T . rugo- sum, T . s i m p l e x .

CD $318 1216), -466 (248),

84. THALISAMISE (155)

h lP 191-194: -138 (CHCls). (155)

L-1- 284 (4.60). (155) NMR 2.31 (1 x S h l e ) ; 3.44 (2 s

OMe), 3.84 (2 x Ol le ) , 3.94 (1 x OMe). (155)

Miss 638 (M+, 36), 219 (loo), 206 (48), 191 (25). (155)

SOURCE: Thalictrum samplex.

85. THALSIMIDISE (thalcimidine)

C39H42OiS2:638.299203

(237) C~-H,,O-S~:fi22.267903 " ~~" - ~ ~

XP 195: [all4 +48 (CHC13). (156) UT- 280 (4,.12), 312 (3.76). (156) ORD Positive Cotton effect, re-

corded only down to 290 nm. 1228)

hlass 622 (If+, 1001, 621 (eo), 607 (56), 591 (20), 485 (lo), 311 (++, 28), 221 (81, 190 (lo), 175 (6). (237)

SOURCE: Thalictrztm s imp lex .

86. TH.ALSIVISE (thalcimine) (151)

RIP 149-150; [a] +22.6 (CHC1,).

US- 282 (4.23), 312 13.90). (238) ORD Positive Cotton effect, re-

corded only down t o 290 nm. (228)

S R l R C j D j S : 2.29 (1 s SLle ) : 3.47, 3.51, 3.89 13 s OMe), 3.82 ( 2 s 031e). (1.51)

C3sH~oOiPITz:G36.283553

(151)

JAS-FEB 19 i9 ] GUHA ET AL. : BISBESZTLISOQUISOLISE ALKALOIDS 49

TABLE 4. Continued.

R2 = R s = R ? ' = Ra' = ?rIe,R = H, R ;-R6 =

(Enantiomer of (Tpnortenuipine) CH,,Ri=H .Ri '=H,

R ? = R - = R >= R?'=R;'=lIe,R5-Ra =

(= j-Tenninine CH,,Ri=FC:,'=H. . .

E, = R = R = Fi? ' = R a =Me, Rj-R6 =

(Epimer of isotenuipine) CH~,R!=H, .RI '=H : ' . . . .

. .

Type X

l-R,l'-S

1-5 , 1 1-s

1-R ,1 I-R

1-S , 1 1-s

l1a-s 636 (NL, I O O ) , 635 O W , 621 (5l) , 605 i l i ) , 499 ( l l) , 318

190 i l l ) , 1 i5 (51 , 174 ( 7 ) , 90 (l5), 89 ( G J . 123;. 2391

(tf, 24), 235 (12), 205 tu),

DEGADATIOS': IIetal-ammonia.

SOVRCEG: Thalictriini rocliebrii- ( K j

~t ia i i i i i i i , T . rir,oosiini, T . s imp lex .

87. I~OTESUIPISE (85) C3sH rc,O;S, :636.283553 11P 239-241: +129 (CHClsj.

(85) U I - 9 5 5 EtOH; 210, 282. (85) XAIR 2.30, 2.58 (2 s K l I e ) : 3.16,

3.60, 3.75 ( 3 x Olfe) ; 5.9 (1 x

3 1 . k ~ ~ 636 (11-1, 485, 395, 198

SOURCE: Dapiinatidra spec ies .

-OCH?O-). (85)

( f - ) . (85)

ORE'S915 (23G), t131.8 ( 2 8 2 ) , '146.3 12811. 121.5) \ - - - I I - - - , , ~~~.

Mass 8 2 2 (Af-), 621, 471, 431, 430, 382, 381. 3 6 i , 350, 335) 321, 192, 191 (++:I, 174, 168 iff), (203)

SOURCES: Dabhnandrci sbecies

89. (-)-SORTESCIPISE (8Gj [at first erroneously named .\--demethylt enuipine (82 !]

CsiH3jO;S* :G22.207903 ?\IP 211; [CY.]" -218 (CHCl,,I. (82) STAIR 2 . 3 2 , 2.63 (2 x S l I e ) ; 3.33,

3.78 ( 2 x OMe). (8G) SOURCE: Daphmi idrn !enziipes.

90. REPASDISISE f8G) C:,H4,0rS2:G36 ,253553

SOURCES: Dnpi ivandra d i e l s i i , D . MP 243: [CY] 0. 1817)

r e p a d u l a : D . ieiiiiipes.

MP 140-14;, 219 'CY.]?{ +223 5 fCHC1 I ISGI

UT 280 (3 8 2 ) 185) ORD -F23 i22S1 -1284 ( 2 3 S i ,

-878 (244, . ( 2 1 5 1 SMR 2 32. 2.63 1 2 1 S l I e I :

3 3 3 . 8.78 ( 3 1 OMe t (851 j.15.

Uiss G3G (11-1. 635. 485. 445> 444) 396. 395, 381. 364, 349. 335, 316 (++). 198 ( L - J , 192, 175 (I+), 174. (2031

JOURNAL OF KATURAL PRODUCTS [VOL. 42, NO. 1 50

TABLE 4. Continued.

Rz = R a = R 4 = R z l = RBI = Me,Rj-Rs =

(Enantiomer of (+)-tenuipine) CHZ,RI=H ,J,Ri'=H,. . . . . . . . . . . . .

Rz= &= R a = Rs= Rzl= Rt l=Me,

(7-0-Methylbelarhe) R1= R1'=H,ll, . . . . . . . . . . . . . . . . . .

l-R,l'-R

Type XI

1-R , 1 I-S

1-R, 1 I-S

1-SJI-s

DEGR $DATION : hletal-ammonia.

SOURCES: Dnpiinandra species unnamed, D . tenuipes .

92. (-)-TEATIPINE (85)

(86)

C3sH,,O;Sz:636.283jj3 1IP 110-145; [a]" -258 (CHC13).

182 I

OR%'- 703 (232), - 1040 (239), ShIR Same as (+)-tenuipine. (85) SOURCES: Dapiinandra dzelsiz, D .

-450 (250). (215)

93. BELARISE (37) C3,HicOs~z:608.288638 IIP 158-160: [a] -222 (CHC!s).

(2i) SGR (3i) Miss 608 (AI-), 607, 501, 471, 417, 416, 382, 381, 367, 192, 191 (++I, 174, 168 (++I. (240)

DEGRADATIOS : Metal-ammonia. ( X i ) \-. ,

SOURCE: Berber is laurina.

94. 0-METHYLISOTHALICBERIIVE (si)

Cs~H~z06Nz:622.304288

(39) NMR 2 38, 2.60 (2 x S M e ) ; 3.51, 3.79, 3.84, 3.91 (4 x Oh'le). (39)

&lass (39) DEGR4DATIOS: Metal-ammonia. (37, 39)

SOLRCE: Berber is laurina.

RIP 208-209; [a] -195 (CHCla).

9.5. 0-~~ETHY-LTHALICBERIIVE

UT 278 (3.65 j. 1243) ORD +510 (245), -312 (280),

Cd9O 1306). 1228) SLIK 2.li, 2.83 (2 i S h I e ) ; 3.61 (1 x OMe), 3.75 (1 x OhIe), 3.87 (2 x Ohle); 5.94, 6.15, 6.51 (3 x arom. H), 6.59 (2 x arom. H), 6.83 ( 2 x arom. H), 7.22 (2 x arom. H). (243)

Mass 622 (AIL, 52), 621 (26), 607 (6). ,591 121. 396 1100). 381 (18).

DEGR~DATTOIV: Metal-ammonia.

SOURCES: Tiialzctrum lucidum, T. (241 1 miiius, T . revolutum, T . thunbergzi.

JAN-FEB 19i9] GUHA ET SL. : BISBESZTLISOQUISOLISE ALKALOIDS 51

T ~ B L E 4. Confiiizied.

l-S,l'-S

12-0-Met hylt halme t hine . .

(244)

rei.olziium. SOURCES: T h f l / Z C t 7 U ~ l ~ I I ~ ? z ? { s : T .

97. THALICBERISE (241: 242j

LIP 181: $231.2. (160) C j;H 4180 $\;2,: 608.288638

UT- 282 '13.81). (141 j

;395 (285) . (,141) S h E i 2.10, 2.58 (2 x S M e j ; 3.66,

3.77, 3.88 (3 s OIIe ) : 6.07-7.20 (10 x arom. H ) . 1141)

X~SS 608 N-), 607, 501, 485,,417, 418, 396, 395, 381, 304 (++)L 198 (+- j , 192, 175 (+-I> 144. (240)

DEGR-ID-ITIOS: Metal-ammonia. 1241)

SOURCES: T1ialictriii)i Iircidzini: T . ?~~ i i tu s , T . i h u n b e r g f i .

CD $2490 (214), -122 (250),

1245 I . SOURCE: Thalictruni foe i zdz i v z .

Type XI1

1-s 98. TH ILVETHISE (244) Cg6HgsO~S*:592.25;338

Miss 592 iW-), 591 (93!, 577 16), 545, 469, 295 (-ti-), 273 (T+).

' RIP 275-277: [a]*' 7200 . (244)

1

I 12401

CjcH,,O-S,.638.299203 1IP 168-170: [a;'' -88.6 (CHC13).

US- 2 i 0 (3.87), 285 13.87). (246) OED -120 1230), $33 (24B!, f2.5

(2GO), +30 1278), -33 (295). 12281

(13gi

SiTF2.32, 2.70 ( 2 s S?\l~j: 3.32, 3.51, 3.77, 3.89 (4 s OlIeI ; 6.33 ' ( 2 x arom. H ) , 6.40 (1 s arom. H ! , 6.47 ( 2 x arom. H I . 6.75 12 x

1 aroni. H ) . 1246) bI.iss 638 (LI-, loo), 637 (4W, G23

(9) , 6!-7 ( G ) , 515 ( 2 ) , 417 (63) , 402 (01) 71.3 (67). 206 (IS), 190 ( E I ) , 176 yi), 174 ( 5 ) , 90 (4), 89 ( 2 ) . (239)

~ DEGR LD.ITIOS: Metal-ammonia.

52 JOURSAL OF SATURAL PRODUCTS [v-OL. 42, NO. 1

TABLE 4. Continued.

Rz = RB = R = R = R 2 ' = Ra = Rql =Me> RI =H, ,RI ' = H I , , , . . . . . . . . . . . . . . . (12-O-Meth~-lthalfoetidine)

Rz= R3= Rz'= R3I= R4'=RIe,R4=Rj=H, RI=H,,R1'=H,,I., . . . . . , . . . . . . . . . . . . .

l-S,lI-S

l-S,l'-S

1-s , 1 1-S

Type XI11

1-S

lo(). T H 4 L I D b I h E (194) CssH,.O;Sz:6.52 314853 RIP 105-107; [.Izi -70 (JIeOH).

(1 44') U?-;?; (3.66), 282 (3.66). (194) ORD>-120 (232), $40 (248),

$10 (260), +35 (271), -35 (295).

KbIR 2.25, 2.62 ( 2 x KMe), 3.27, 3.50, 3.75, 3.87, 3.91 (5 s 0AIe); 6.30-7.54 (9 x arom. H). (194)

RIsss 652 (M-), 651, 637, 621, 515, 426. 425. 411. 397. 394. 331, 330,

(228)

213 (loo), 204, 190. (194, 240)

(194) DEGR~DATION Metal-ammonia.

>SOL-RCES Thalictrirm das>carpum, T . luczduin, T . re~olutzini, T . rzcgoszm

lOOa THALIGOGIDIYE i152a)

. . (152a)

UT- 275 (3.72), 283 (3.72). (152a)

$67 (268). -190 (287). (152a) S L I R 2.25, 2.66 (2 x " e ) ; 3.49,

3.75, 3.86 (3 x Ol fe ) : 6.2-7.7 (9 x arom. H) ; 5.6 (2 x OH). (152a)

hIass 624 (>I+, 40), 412 (7), 411 (20), 203 (++, 23), 192 (100). (152a)

DEGRXDATIOS: Me tal-ammonia.

C D -318 (224), +54.9 (242),

(152a) SOURCE: Thalictruni rugosiiin.

101 TH~LRGGOSIDIYE (152)

MP 172-174. [al30 -185 (MeOH). C3nH<gOt 9 2 r638.299203

(152) VT- 275 (3.99), 282 (3.99). (152) ORD -34.3 (226). t 9 8 12411.

-;-171.5 (248), +58.8 f267): -2203.3.5 1286). ii52)

SMR-2.25, 2.60 (2y?hIe): 3.51, 3 .75 , 3.85, 3.87 (4 x Oxre): 6.3- 7.7 (9 x arom. H). (152)

DEGR XDXTIOS : Metal-ammonia.

SOURCE : Thalictr2i~ii rzigosirni. (153)

102. THALFINE ithalphine) (195, 9) C,;H 3E05X 2 :648.247 168 1IP 141-142: [ c T ] ' ~ $69 (EtOH).

1137) UT- 260 (4.58), 348 ( 3 86). (137) CD 11340 (2081, $670 (233),

(360), +6 9 (388). (144a) NRIR 2.20 fl x K l I e ) ; 3 40, 3.50,

3 61, 3.76 (4 x OlIe) 6.04 (1 x

-820 (263), -280 (229), -13.9

OCHgO), 5.93 (C8-H). (195, 9)

JAS-FEB 19791 GUHA ET AL. : BI~BESZTLISOQUISOLISE .%LKALOID~ 53

TABLE 4. Coiiiiizitcd.

R Z = R B ' = R 3 1 = R,' =Me ,RB = R ,i = H, R i = R i ' = H , . . . . . . . . . . . . . . . . . .

(l14a) DEGR.ID.ITIOS : Met al-ammonia.

1195) SOCRCE: T / i O h C f l l i l l / f G C f i d l i ? i / .

103. TH.\LFISISE i t halphiiiine) 1195. D i

(195) hl.1.; GO6 !11P, 95) ~ 440 (14 ' . 220

11OOl! 204 f l G i . (144s DEGRIDITIOS : l I e t al-smmonia.

(144a~ SOURCE: Thalictuiinz f o e t i d i m .

l-S,l'-R

X ~ I R 2.30. 2

6.28 Cc & C,' Xiqs GO8 N - j ,

381. 367. 304 1++

,65 ( 2 s S h I e ) ; 3.48 ci; O ~ I ~ J , 3.93 ( 2 s OAIe): 6.0,

Hi. (247) 501, 487. 471, 382,

), 181 1 + t , ), 175 ( I T ,

I+, 7 ) . 1210) ; : Met al-ammonia.

D E G R ~ D LTIOS: Metal-ammonia.

54 JOLRNAL OF NATURAL PRODUCTS [VOL. 42, so. 1

TABLE 4. Coztiimcd.

Rz= R3= R2'=R3 '=R4 '=Me,R4=H, Ri=H,,Ri' = Hii'!, , . . . . . . . . . . .

Rz= R?= R 4 = Rn'= R4'=?\le,R3'= H,

(Epimer of lauberine) R1=H,,RI'=H1,1;. . . . . . . . . . . . . .

. .

I ' I

l-R,l'-S

l-S,l'-S

l-S,l~-S

1-s, 1 I-s

Type XV

1-R,l '-R

106. LAUBERISE 139) C3 iHdcO~S2 :608.288638 1IP unstable, 250-255 (hydro-

bromide); [a] +481 ICHC13). 1541

NiyR 2.30, 2.65 (2 x S l l e ) ; 3.92 (2 x OXle), 3.95 (1 x OXle); 6.06,

llass 608 (XIL), 501, 471, 382, 381, 367, 304 (++), 191 I++, loo), 183 ( S f , 71, 175 (++, 81, 168 ( i s , 20). (240)

DEGRAD ~ T I O S : Metal-ammonia. (39)

SOURCE: Berber i s laur ina .

6.12 (CS I% Ci' H). (247)

10Ga. THABADEMIXE (157a)

Da ta not available t o the reviever SOURCE: Thalzctrztnr sirlianabadense.

107. TH~LICTISE (161)

11P 226-228 (nitrate); [a] -15.8

UT- 284. 1161) S M R 2.19, 2.62 (2 x Nhlej: 3.62,

3.82, 3.86 (3 x OMe); 5.84, 6.01 lCer and C.-H'I. 1161)

C,,H,,OENz:594.272388

C3iH4cO6Nz:608.288638

(CHCl?). (161)

hlass 608 (?*I+), 396, 395, 381, 205,

DEGR~DATIOS: Metal-ammonia. 198, 190, 175. (161)

(161) SOURCE: Tkal ic t rz~nz thiinbergii.

108. THALMIKE (248)

1IP 253; [a] 64.5 (144) UT- 286 (3.65). (227) ORD -25 (250). -30 ( 2 8 7 ) ,

C3;H"oO6Nz:608.288638

$10 (310). (228) NRIR 2.22, 2.64 (2 x SRIe): 3.93

(3 x OMe); 6.06 (CS and C S ~ H ) . (247)

31ass 608 (hl+l, 3 1 , 471, 382, 381, 367, 304 (++), 191 ( -+t IO!?), 183 (Sf, i ) , 175 (++, 81, 168 (ff, 20). (240)

DEGRADATION : hle tal-ammonia. (248)

SOURCE: Thalictrunt nrznzis.

109. KORPASURESSIXE 122) C36H3sOsNz:j04.272988 hlP 175; [a] -250 (CHCL). (22) US- 223 (4.04), 240 (4.30), 288

(4.10). (22) S M R 2.42 (1 x Khle); 3.47, 3.83,

3.91 (3 x 0Me); 5.08, 5.28, 6.08, 6.63 14 x arom. H): G.3-7.24 (6

, x arom. H) . (22 )

- - 93 JIS-FEB 19i'JI GL-HA ET AL. : BISBESZTLISOQTISOLISE ALKALOIDS:

T ~ B L E 4. Coiztinucd.

Rz = R 4 = R5 = R = R31 = Me, Rs = H , ( 2 '-.Y-L\ret hylnorpanurensine) R I = H ; ' , R ~ ' = H , , . . . . , . , . . . . . . . . . . .

Rz= Rs= R 4 = Rz'= Ra'=?rIe,Rj= H, Rl=Hl ,RI'=H,, . . . . . . . . . . . .

0 Me

1-R,l'-R

Type XVI

1-R,l '-R

Type XVII

1-s

1-SJ-s

XISS 594 (AIT, 26), 593 ( l l j , 48T ( < I ; , 473 ( l ) , 45i (2 i , 367 (loo), 206 ( l l j , 205 (E), 192 C8:h 191 (IO), 190 ( 2 3 ) , 184 (92), 116 il4), 168 ( 5 1 , 161 (26), 160 (7). ( 2 2 )

SOKRCE: d bii ia paizzirevsis.

110. PASERES~ISE ( 2 2 ) Ca,H;.,06S,:608.288038 31P 156-1581 [CY] -245.6 (CHCI:).

i22) U T - 225 (4,38:1, 238 (4,551, 284

(4.221. ( 2 2 )

5.82, 6.61 (4 s H): 6.42-7.26 ipro- tons). (22 )

SLIR 2.40, 2.55 ( 2 s S l I e ) : 3.46, 3.82, 3.92 (3 s OLIe); 5.02, 5.24,

Xiss GO8 1MT, 73; , GOT (43) , 501 (611, 487 ( l j , 471 ( 2 j , 381 (lo!), 192 ! X i , 191 (781, 190 ( l G ) , (1@1, 174 (15,1, 168 (17). C W

DEGRID.ITIOS: ?\Ietd-animonia. ( 2 2 )

SOURCE: A b i i t n pamtreizsis.

1111; UI- 211 (4 .S i , , 284 (3.98). 1111) S L I R 2.57 12 s SLIe) : 3.42, 3.80,

3.85 (3 s OLle), 5.77 , 6.07, 6.17 13 x arom. H ) , 6.8-7.9 (T s arom. H ) . (111)

?~IASS GO8 ChI-, loo), GOT (SO), 593 ( 5 ) , 577 (161, 396 ( 3 6 j , 395 BT), 381 (831, 204, (331, 198 (79) , 190 154): 177 (38) , 175 (41), 173 (391, 159 UT). (111)

DEGR-ID-~TIOS: Metal-ammonia. 1111)

SOURCE : ,?-eni iia roil rieil lardii .

112. TH.II.IBRUSIMISE (151) CasH,,OjNz:652,2784G8 l f P 198-200; [CY] +28 (CHC131.

(151 1 U T - 241 (4.481, 283 (4.02), 300 .qh

(3.91). (151) S M R C5D,S: 2.38 (1 s SAIe); 3.21,

3.55 , 3.79, 3.83, 3.88 (5 s OLIe); 4.40 (benzylic methylene); 6.42- r - 1 .s8 18 s arom. H ) . (151)

ii.iss 652 (AI-, loo), 651 (85). ( i a j SOCRCE: Tlialicfrztnr

rocliebri~nianztnr .

113. THALIBRIXISE 12%) , C 39H140~S2:668 ,309768 i M P 172-173; !cYJ~~ +160 (XeOHj. ' (149)

56 JOURSAL OF SATURAL PRODUCTS [VOL. 42, so. 1

T ~ B L E 4. C o i i f ? i w d

I UT- 205 (5.01), 242 sh, 281-2 (3.93) 1 (119) CD -1690 (245), -472 (274,,

Ti080 (296) (236) NRIR 2 45, 2 58 ( 2 x K l I e ) , 3 16,

3 36, 3 7 7 , 3 82, 3 89 15 x 0 M e ) ; 5 90, 6 39 12 x aroni. H ) . (236)

Miss 668 (RI-, 5 3 , 425 (53), 213

and neak peaks at 561, 510, 476. (236)

DEGRADITIOX . RIetal-ammonia. (236)

SOT. RCE Thalzctrum rocliebrzciiiaizzci~i .

(T+, loo), 234 ( 5 ) , 192 (TO).

Rz= R3= R2'= R3 '=Me,R4=H,R1= R1'=H, stereochemistry undetermined

R3 = R 4 = Me,R4' = H,R2 =Me and Rp' =H or vice versa, R1=R1'=H, stereo- chemistrv undetermined

Rz= R3= R4=Me,R2'= RS1=H,R1 = R1'=H, stereochemistry undetermined . (2'-N-Demethyltiliacorinine)

Type XVIII

114 DINLL K O R I ~ E (162, 249) C36H,c0,Nz 576 262423

UT- 22% 14 i o ) , 236 sh (4 68), 294

1IP 238-210. [a]" +42 55 (CHC13). 1162)

(3 97)- (162)

1290) (162) XlIR 2 29, 2 61 ( 2 x NRfe), 3.23,

3 93 (2 x 0lIe) 6 31-i.88 (9 x aroni H) (162)

Miss 5T6 (lI-, 75), 350 (G), 349 (loo), 335 (35), 175 (50). (162)

SOURCE Tilzacora ditiP1agez.

CJI -106 1230), +672 (250), +396

115. No1 tiILLI.IcoRI?*'E-,i (iso- tiliarine). (166)

(1AG)

C,jH3~0jS~:562.246fi3 RIP 258-260: [a] f194.5 (CHCI,).

U T 215 14.80). 235 sh 14.69). 293 (4.00) .~ (1G6j

S l I R 2.28 (1 s K l I e j : 3.51, 3.93 (2 s Olfe ) : 0.7-3.3 (6 s -CH,-); 6.26-7.95 (9 x arom. H ) . (166)

(loo), 321 (24), 168 (42). (166) , h 1 . i ~ ~ 562 (AI-, 69), 366 ( 3 5 ) , 335

1 SOL~RCE: Tiliacora ,fidn*ra.

116. NORTILI-ICORINSE-.I (pseudo- tiliarine) 1168, 169)

C3jHL40jl;2:562.246773 MP 262-268; [a] $268.8 (pyridine).

(169)

f l M ) 1IP 252-254; [a]'* +325 (CHCl,).

1 UT-212 (4 i s ) , 236 sh (4 E), 292 (3 99) (166)

-CH,-) 3 80, 3 92 12 s Oble), 1 A 26-8 08 19 x arom H) 1166)

NRIR 2 30 11 x S l l e ) , 2 8-3 07 f6 x

I RI.iss 562 (lb, loo), 336 '(36), 335 , I SOI-RCES: Tiliacora d i n k l a g e i , T .

189), 321 (22), 186 (40). (166)

I fztnifera, T . raceiiiosa.

- - LIS-FEB 1 9 i 9 ] GUHA ET AL. : BISBENZI-LISOQUISOLISE ALKALOIDS 31

TIBLE 4. C o n t i w e d .

Type XX

R l = R3I= H,R: = R,= R2'=31e,R1 = Ri' = €1, stcreocliemi~try undetcrrnined

= I?, = I{,= I??' =1\Ie,R3'= H, R . H, ,RI' = H . . , , . . . . . . , . . . , (Epimer of tiliacorine)

R? =R3 = E:: = R j =l \ le ,R2'= R, '=H,Rl = R I ' = H, stereocheniistrj- undet@lmined,

Rz = R, = R, = R R? = I: 1' = H ( 7 , i I-0,O-Diniethylisochondodendrine)

= R3' = R,' = Me ,

l-R,l'-S ~

1-s ,1'-S

Type XIX

117. SORIILI.ICORISISE-B (169) CsjH:~OLS?:502,246ii3 M P 218-220; :a! +356.2 ipj-ridine;).

1169) S I I R 2.23 (1 s Sl\Ie) : 3.75 ( 2 s

OlIe I : 6.38-8.20 (9 x aroni. H!. (169)

SOL-RCE: Tiliqcorn mcei i iosa .

119. TILI.\COP,ISISE (169, 249a) C-~H:iOjS?:576.26213 1IP 195: ral 1310 ipyridine). (169)

S l I R 2.28! 2.62 12 I S l l e ) : 3.S2,

DEGRADATIOS: Hofmann. (169) SOURCES: Ti l iacora d i n k l a n e i , T .

L7- 290 13.95). (1691

3.85 ! 2 I OlIe'i. (le91

120. TILI.~XOSIS~ (16s) C,4H,,O~r?:5~2.23733S \IP 276-277 (ace ia te ) ; :a'" -530

(CHCl:). (acetate). (108) SOCRCE: Ti?z'l;cora mcei i iosa .

(10 x arom. Hi. (59) M i a s G22 ilI-. 29). 621 (81. 313

/26), 312 (100). 311 128). 201 (29). 190 i l i , , 151 (li), 1.59 ili), 146 (7 1, 145 (8). (59)

JOURSAL O F SATCRA4L PRODUCTS [VOL. 42, 30. 1 TABLE 4. C o n t i n i d .

R2= R3= Rzl= R3'=Me,R( = R,' =H, Ri=Ri'=HIIII.. . . . . . . . . . . . . . . . . . . . .

Rn= RZ1=1Ie;R3= R3' = hle and Rb= R, '=H or vice versa, R , = R I ' = H , stereochemistry undetermined.. .

R1= R;= R4=R2 '=R3 '=~ le ,R4 '=H,

[Enantiomer of (- )-noreyeleanine] Ri= Ri'=H,. . . . . . . . . . . . . . . . . . . . . .

R2= R 3 = Rb=Rz1= Ra '=Me,RI '=H,

(7-0-Methylisochondodendrine) Ri = Ri ' =H~III. . . . . . . . . . . . . . . . . . . . . . . .

1-R, 1 I-R

l-S,l'-S

l-R,ll-R

DEGRADITIOS: Metal-ammonia. (178)

SOURCES: Cliondodendron toniento- srim, Cissanipelos in su lar i s , C . pare ira , Cyclea in su lar i s , Epine tr i in i cordifoiizcni, E . wan- genotti , E . d l o s i t t n , Herac ieum w.zllichi, Paracyc lee ochiuiana, Siepliinin capita t u , 5'. cepharanthn, S . rotzinda.

122. ISOCHONDODE~DRINE (iso-

Cs,H 3r@8S2:59-l ,272988 hIP 305. CY]^^ f120 (0.1 Ii HC1)

bebeerine) (250)

i.52) LlP380; [a125 +59 (pyridine). (11) UT' 211 (4.72), 231 sh (4.58), 278

( 3 . 7 3 ) , 285 (3.72). (59) ORD -990 1240). -60 12523,

-280 (2663, 4400 (288). ($9) IihlR 2.27, 2.53 (2 x Nhle); 3.87

(2 x OMe), 3.82 (ring -CH,-). (216)

(4), 312 (a), 299 (14), 298 (loo), 29i (20), 191 (9), 190 ( i) , 162 (6). (59)

DEGR.ADATIOX: Metal-ammonia. (250)

SOURCES: Abzita candicans, Cliondodendron liniacii foliunz, C. nricropliyluni, C . platipliyliitii, C. foincntoszttn, C . ioxicofeferziwi, Cissait ipelos nizicronata, C . pare ira , Cyclea barbatn, C . in- sitlaris, C . inadagascariensis, C . pe l ta ta , Epirietri im cord$olizc.m, E . niangenoiti , E . ;'illoszini, Gztatteria megaiophyl la , Herac leum wal l ich i , Isobona p i lo sa , Paracyc lea ochiai- ana, Pleogyne cunninghami, S t ephan ie 1iertiandi:ToIia.

MASS 594 (?\I+, 60'1, 593 (14), 487

123. SEOPROTOCURIDISE (251) C 38H sN :594.272988 M P 232: Tal 0. (251) Source: 'Crirark.

124. (+)-SORCTCLEANISE (50)

RIP 249-251; [cyjll +26.54 (CHC13). C".iH,[OsS~:608.288638

,-7, i '0

SOURCES: Ckondodemiron l imacii- fo l i z rnz , Cyclea i n s t i l a r k , Epine tr t tn i z~il!osziiit.

125. ( - ) - N O R C T C L E ~ I X E (252)

LIP 246-2463 [a]24 -22.50 (CHC13). Cq-H,tjOsK? ,608,288638

i R R ) LK-229 (4.76), 276 (3.84). (88) NhIR 2.35, 2.49 (2 x Nhle); 3.41

(1 x 011e), 3.6i (2 s 0Me) . (216)

JAK-FEB 19791 GUHA E T AL. B I S B E S Z Y L I S O Q U I S O L I S E ALKALOIDS 59

TABLE 4. Coittinzred.

Rz= R,= R L ' = R3l =Me,R3= PI,' =H, RI = R:'= €I, stereochemistrj- undetermined

R2= R2 '=Me,R3=R4= R,'= P\,l=H, R1= R,'=H,

1-s , 1 1-R

1 I-R

l-S,l'-S

Type I X I

l-R,1'-,3 i

DEGR~DITIOI : Metal-ammonia.

SOURCES. Chondadendro7i toinen- tos i in i , Cyclea ?nsu lar i s , Epi- nefr ic i i i cord~.t"oliztrn, E . uiaiigenoiti .

(252)

126. PROTOCCRIDISE (50) Cs~H,~(?eS?:594.272988 hIP 295 (pyridine adduct); [a]

SOCRCE: Czcrare.

S7.G (H20) (hydrochloride). 1251)

127. ~ C I I D E A I S E (119)

PIIP 251-256 -a:3O -13 (pjridine),

VT- 277 f3.18). 283 (3 .47) . 1119)

C,;H: OsS2.608.288638

r .a,- -no - 15 (CHC13). (119)

S M R 2 .23 , 2 : i i (2 :: SPIIe)': 3.40, 3.80, 3.82 (3 s OhIe); 5.70-G.85 (10 s arom. H ;. 1119)

Mass GO8 ( A l l ) , 607, 312 (loo), 298,

DE G R . ~ D . ~ T I O S : Met 31-ammonia.

SOL-RCE: S c i a d o f e n i a fox i fera .

128. SCLLDOLISE (120)

204, 191, 190. 1119)

(119)

CssHc,OsS, :590.211688 LIP 225-2281 [a]** -4G (CHC1,).

112n1 L-?-iii (3.94): 2S3 sh (3 .88) , 326

sh (3.771, 335 (3.78). (120) S M R 2.35 (1 s S l I e ) : 3.55, 3.83,

1.02 13 s 031e). 5.50-0.85 19 s

(120) SOUECE: Sciadotenia iosc fera .

l28a. TETRI-0-DEUETHYL- CYCLE.lSISE (252Zi)

C31H3:0eS*:566.241688 Data not available t o the revieFer

129. CHOSDOCCRARISE (193)

LIP 277-280 (iodide) : [a]*5 +l50 iH,Oi (iodide). (51)

SOTRCE: C h o n d o d e n d r o n

CssH,,OJ-- 2X1:G2.1.319938

U T - Hz0: 280. (31)

toii ieii fosii i i i .

130. CHOSDROCL-RISE - 1 7 1 - tuhocur~ne] 1193 I

S HC1). ( 5 2 I

CjsHj*O&s 591.272988 1IP 232-231. [a]'' f200 (0.1

JOURNAL OF KATURAL PRODUCTS

TIBLE 4. Continited.

[VOL. 42. NO. 1

R, = Rj = R,= R p t = Rgl=l le ,R5 = H,

[i-0-Met hyl- (+)-curine! R i=Rl '=H, . . . . . . . . . .

Rz = Rs = R, ' = R s l =Me ,R? = Rj= H , Ri = RI HI,' . , . . . . . . . (Enantiomer of (+&curine)

RZ = R, = E: p l =Ale, R, = R5 = R,' = H,

[GI-0-Demethyl (-)-curine] R i = R i ' = H ' . . . . . . . . . . . . . . . .

l-S,l'-S

1-SJI-s

1-R,l'-R

1-R 1 I-R

IR 2.25, 2.45 (2 x > (ring -CH,-); 3.82, 3.88'(2 x OPlIe). (21G)

llass 594 Of-), 593, 579, 298 (loo), 297, 296, 266, 251.5 (++), 191, 190, 162. (253)

DEGRAD ATIOK : Met al-ammonia . (254)

SOURCES: Choiidodeiidroit tomento- sztiii, Cyclea iiiadagascarieiisis.

131. CHONDROFOLISE (255) Cs;H.cOz~*:G08.288638 Alp 135; [a220 -280.6 (0.1 S HCl).

12n) N i R 3.74 (1 x O l I e ) , 3 85 (2 1

OXe). (255) 111s~ 605 (MA), 607, 593, 487, 312,

298, 297, 258 5 (+l), 204, 190, 174, 159, 146, 145 (253)

SOURCES Choiidodendroii plaiz- p1~y11zti1i, C i a r z a o:aia.

132. ~ ~ ' - C U R I ~ E iberbeerine

ll;;s'594 (AI-), 593, 298 (loo), 297, 283. 1257)

SOURCES: db i i ta c a n d z c m s , Bzixzis seii iperizreiis, Clio?idodendroiz i i i i croph3lzm. Sec fa i id ra rodzei.

133. (- )-CL-RISE [(-)-bebeerine] 1254)

C36Hs606Sz:594.272988 MP 1G5167: [a]*[ -280 (0.1

11P 221; [a125 -33i (pyridine). (11) VI- 206 14.95), 225 sh (4.Gl), 282

S HC1). (52 )

, . . (3.98): (215j

ORD -il (231), -9G5 (239), -79 (280), -319 (292). (215)

M I R 2.30, 2.4i ( 2 x KMe): 3.93 ( 2 x ORle) ; 2.88 (ring -CHp-). (216)

MASS 594 (ML), 593, 579, 298 (loo), 297, 296, 2GG, 251.5 (++), 191, 190, lG2. (253)

DEGR.IDAT1OK : Met al-ammonia . (173, 254)

SOURCES: A ristolochia indica, Choizdodendroii p laf iphylz tni , C . toiiientoszt?n, C . tosicoferziiii: Ciss- aiiipelos pare ira , Cyclea nzada- gascar i emis , Isoloiia p i losa , Paracyclea ochiaimia, P l e o g y n e ci~itiiinghamii.

134. CYCLEACURISE (79) Cj,HsaOfNz:580.257338 RIP 205208; [a] 2 5 - 202 ihIeOH) . (79)

JAS-FEB 19'791 GUHA ET AL. : BIGBESZYLISOQUISOLISE ALKALOIDS 61

TXBLE 4. Continired

T\- 95% EtOH, 284 (3.83 I S X K DMbO, 2 18, 2.48 (2 x S M e ) ,

~ I ~ s s 580 fJI-, 521, 298 (10Oj, 2 9 i

DEGRID ITIO\ Metal-ammonia

(79)

3 i5 (1 1 OMe) (73)

(541, 253 1291 (T9)

Rz= R2= R2'= R3'=l\ le,R,= R j = H , R i=R: '=H . . . . . . . . . . . . . . . , . . .

Rt = R3 = R 5 = Rl' = R? ' =Me , R 2 = H, R, = R. ' = €I . . . . . . . . . . . .

Rs= K3= Rj=R2'= Ra '=Me,R,=H, R,= R , '=H, [12-O-Meth~-l-(f)-curinej

. . . . . . . . . . . .

' I

1-R ,1 1-R

1-s, 1 '-R 136 HXTXTIDI\E (258)

MP 1i9-180, [a: -109 (pyridine).

UT 805 EtOH 280 (3.07). (258) S U R Discussion mithout data

1 1 ~ s ~ GO8 (AI-). 593, 501, 487, 312,

DEGRXD XTIO\ Metal-ammonia.

~ O L R C E Cissnnipelos parezra.

C,-H,,O,S, GO8 288638

(258)

(258)

298, 296, 258 5 (+-), 191, 130, 174, 162, 148, 145 (258)

(258 1

1 3 i . HAI-.~TISE (259) C36Hj,OgS2 : 594.272988

U T 7 2 i i t 3 . i 3 j J 283 (3.75). (11) DEGR.ID.ITIOS : Met al-ammonia.

11P 298-303; 'aj 0 . (259)

(2.59 1 \ - - -

SOCRCE: Cissnoipeios pore i re .

138. H.II-.ITISISE (280)

L-1- 0 . 1 s HC1; 280 (4.16). (261) l DEGRIDITIOS: AIetal-ammonia

~ sOCRCE: Cissaiiipelos pare ira .

C3;H:oO~S,:608.288638 AIP 231-2321 [a: - 5 . (2Gl)

(260)

~

1 191. 190, 162. ( 2 5 3 )

1 L . i S i !508~(llP)j 807, 593, 487, A i l , , 312; 311, 298, 296, 258.5 ( j + j ,

DEGR.ID.I~IOS: Metal-ammonia. ( G O ) , SOURCE: Cissuiiipe?os poreirci

l-E,l'-E 140. ~~'-O-METHTLCLRISE (89) C -H, OJ?:GO8.288638 1IP 162-164: [a]" -303 (CHCls1

62 JocRxL4L O F NATURAL PRODUCTS

TABLE 4. Continued.

[VOL. 42, KO. 1

1:l molecular complex of (-)-curine and (-)-tubocurine..

Enantiomer of (+)-tubocurarine

Rt= Ra = Rzl= R3’=AIe,R ,= R: = H ,

(Enant,iomer of chondrocurine) Ki=Hllli,R1’ =H,. . . . . . . . . . . . . . . . . . . . . .

l-R,ll-S

1-R ,1 ‘-S

Type XXII

1’-R

Xiss 608 (AI+, 82), 312 (lo@), 298

SOURCE : Guat teria niegal o p i q l l a . (76), 296 ( 7 6 ) . (89)

141. TOXICOFERISE i54’16 AlP 286: [a] -263 IlXHCl in

DEGR.~D.\TIOS : Met al-ammonia. EtOH). (54)

(54) SOURCE: Cliondodeiidroit

toxicoferzrin

142. (+)-TUBOCTRARINE (193)

MP 275 (chloride): [a]20 +215 C~~HI ,O,S , -+ 29-:609.304210

(H20) (chloride). (51) UT- H,O: 280. 151) DEGR A D ~ T I O ~ : Metal-ammonia.

SOURCES: d n o m o s p e r n m m grandi- (193)

folziini, Chondodendroii fo ine i i tos im.

143. I - \-Tvnocrn \RISE (53) C2,HliOFfi2++ 2X-:609.304210 ’ LIP 2 i 5 (chloride): [a]20 -258

(H20) (chloride). (53) SOURCE: Choiidodendroii

t om en t osi~nt.

Pure compound could not be iso- lated, physical properties could not he determined. SOURCE: Chondodeiidron

tox i co je r im .

145. CISSAhIPAREIKE (191)

LIP 239-240; -111 (CHCl,). C3iH350,N2:606.272988

f.i8’i U?-2k2 (4.0), 320 sh (3.60). (58) XYIR 1.99 (1 x SRle): 3.75, 3.85,

3.92 (3 .y 0LIe); 5.15 (1 x’Ar- ’

CHq-OR 1. 1191) hlassk06 (AI’), $02, 500, 312, 310,

DE GR DATION : RJet al-ammoo ia. 206, 204. (191)

(191) SOURCE: Cissmiipelos pareira.

146. DIHYDROV. ARIFTEINE (57)

hlass 594 (>I+), 490, 403, 297, 191.

SOURCE: Cissanipelos oiali folia.

147. DI\IETHTLDIHYDROITARIFTEIP;E

C3sH3,0sS*:.i94.272988

(57)

(,57)

6Tosicoferine is retained in the table since Cava et a l . (54) though, that in “vie%- of its ease of isolation and its apparent behaviour as a single compound, i t will undoubtedly be encountered in future phytochemical investigations”.

JAN-FEB 19i9] GUHA ET AL. : BISBESZYLISOQUISOLISE ALKALOIDS 63

TABLE 4. Cont inued .

R , = H, R 2 = Me o r v i c e versa

' R 4 0 ' R , = H, R,= Me or v i c e versa

R , = H, R + = M e o r v i c e versa

R2 '=R3 '=Me,R2= R s = H , R1=H,,RI '=H'". . . . . . . . . . . . .

1 1-11

1'-R

Type XXIII

1 l-.S,l'-S

C,,Hd,O&P :622.304?88 1I.iss 622 (JI-), 518, 503, 417, 311,

SOURCE: Cissniiipelos oraltfolaa. 204. ( 5 7 )

137, 429,'311.' (57) SOURCE: Ciscanipelos ozalz'folia.

14G. METHYLDIHYDROTT-ARIFTEIKE (5; !

Cz;H:s 06Sz :608.2P8638 MISS 608 111-1, .504, 417, 311, 190.

SOT-RCE: Cissniiipelos oimalgoiia.

150. ~IETHYL~T-.~RIFTE:SE (57 ) C1;HzjOES2:606.2729ES Xiss 606 (II-), 502, 486, 459, 430,

SOURCE: Cissanipelos ozlalqolia.

( 5 7 )

312, 311. (57 )

151. \T.\RIFTEISE ( 5 7 ) Ci,11360ES2:592.257338 11.1s~ 592 (llT), 488, 473, 445, 417,

SOCRCE: Cis:enipelor orali folia. 416, 297. ( 5 7 )

132. COCSOLISE 12662) C IrH -20,S2:548 ,231 123 MP amorphous powder: [a] +204

U T - 225, 277 sh, 291. (66) S l I R 2.58 il x h X e ) , 3.87 (1 x

n1Iel; 2.65.7.40 (4 benzylic and 8 ring methylene protons); 3.61- 4.0 (10 Y arom. H ) : 4.33 (tm-o

(CHC13). (SO)

deuterium exchangeable protons) (262)

(661 MISS 548 (AI-), 336, 335, 321, 168.

SOKRCE: Cocculus peuditl i ts .

1-S,l'-S 153. COCST-LISE (eferine, trigille- tine) (66)

C3jH3~0,S2:5C2.24GT73 3IP 272-271: [a: 1 2 8 0 ICHC13).

~ (66) ~

1 Uf- 234 (4 .72) , 275 sh (3.731, 289

(3.771, 307 sh (3.59). (175)

64 JOURKAL OF NATURAL PRODUCTS [VOL. 42, NO. 1

TABLE 4. Contkued.

S h l R 2.35, 2.56 ( 2 2: Khle); 2.61- 3.60 and 4.11 (8 ring methylene, 4 benzylic and 2 ring methine protons), 3.90 (1 x OMe): G.18, 6.36 (2 x arom. H ) , 6.58-7.67 (X 1 arom. H) (66)

RZ = R3' = l I e ,R3 = RZ1= H, Rl=H,,R:'=Hl , I . . . . . . . . . . . . . . . ,

R 2 = R3= R2' = R3' =Me,

(Enantiomer of isoirilobine) Ri=HlI ,R,'=H,.

R2= R, = R2'= Rdl=hIe,

(2-~Y-lIeth~-l-12-0-metli~-lcocsoline) R1= H, , P \ i ' = HI

. . . .

1'-R

1-SJI-s

l-R,l 'R

1-s , 1 1-s

11 562 (lI','39); 350 (32), 349 (loo), 348, 335 ( 3 5 ) , 175 (70). (66)

DEGR.\DITION : IIetd-ammonia.

SOURCES: Coccdi ts pendidus, Tri- (66)

clisia gil leti l , T . p a t o i s .

154. 1 , 2 - D E H r D R O ~ ~ I C R , ~ S T H I S E (83)

183 )

Cs4HsaOjN2:54G.215473 h'lP 188-194; [a]20 -150 (CHC13).

Vf7-i35 (3.4). (83) S M R 2.55 (1 x SAIe): 3.85 (1 x

SOURCE: Dnbiiiiandra sbecies OhIe). (83)

unnamed.

(24)

124)

C34H9zOjSz:.j48.231123 l fP 256-258; [a]20 +332 (pyridine).

IJf'233 (4.733, 275 (3.30), 289 (3.84), 306 sh (3.64). (24)

K l I R Pyridine; 2.48 (1 x Nhle) ; 3.80 (1 x Ohlc). (24)

h1.m 548 (lI+, G O ) , 547 (421, 336 (26), 335 (100): 321 (16), 319 (18), 168 (T2) , 167 (16). (24)

SOUKCE : 4 nisocyclea gradid ier i .

Uf%36 (3 3.5). (263) KhIR 2.49, 2.59 ( 2 x Kl l e ) ; 3.84,

3.96 12 x Ol Ie) : 6.13, 6.30 12 x highfield arom: H ) . '(13)

hIass 376 (11-). (13) DEGHADATIOK: Photolysis. (13) SOURCES: Depknaiidra micrcn!ha, P. spec ies D?-7, D . species unnamed.

(190) 157. ISOTRILOBISE (homotrilobine)

CsoHIs05S2:5i6.262423 1IP 213-215; CY.^".^ $293.1 (CHCls).

1263) NhiR2.40, 2.60 ( 2 x K l I e ) ; 3.85,

3.97 ( 2 x OXe); 6.13, 0.30 (2 x high field arom. H) . 113)

Miss 576 fll-), 3.50. 349. 3%. l i 5 (++, 100). (203)

(190) D E G X ~ D JTIOA : Metal-ammonia

US-FEB 19T9] GUHA ET AL. : BISBESZTLSIOQUISOLISE ALKALOIDS 65

TABLE 4. Contirzzted.

R?= RE = H,Rz '= R B ' = l I e ,

(Enantiomer of cosdoline) R , = R , ' , R i ' = H , . . . . . . . . . . . . . . . . . . .

RB = Et,'= R 3 ' = ~ I c : , R, = H, Ri=P, i '=H . . . . . . . . . . . . . . . . . . . (Epimer of 0-methylniicranthine)

R, = R a = It a ' = N e , R y l = H, R 1 = H b ' = H . . . . . . .

SOURCES: Dapiivaridra ~ri icrontha, D . sbcc ies Dt-7, D. sbec ics unnamed.

1-R;l'-S

I l l d l

UT. 227 (-&.GO), 275 ~ 1 1 (3.69i, 284 (,3.71), 304 (3 .44) . (17.5)

S l i R 1nsolubilit~- in c3mriion cir- gouic solvents precluded the re- corciing of nnir spectra. i l i5 )

(1001, 321 (321, 108 (-19). 1175) ;\I.\ss 548 2 ~ ! , 330 (31 I ; 235

SOURCE: Tiiclisiri sii'iccrd,i!a.

sh (4.21), 311 .;h (,3.4G), 351 (3.05). (172)

( 2 s OlIe I ; 5.86-7.29 (10 s aroni. H i . 7.39. 8.34 12 x aroni. H J .

S 1 I R 2.40 11 x S 1 I e j : 3.92, 3.99

66 JOURSAL OF S.4TURAL PRODUCTS

TABLE 4. Conlinued.

[VOL. 42, so. 1

Rz=R3=R2'=RIe,R4=R3'=H, R1 = H, ,R '=HI~~I , . . . . . . . . .

MeNw ' Me \

0-Demet hy1,menisarine (exact location of OH is not determined

R2= RS = Rd= R2'=JIe,R5 =H,Rl = R'= H, stereochemistry undetermined

R 2 = R = R I = Me, €1 rR = CH,, R , = El'= H, stereochemistry undetermined. . . , . . . . . . .

Type XXIV

1-s, 1 I-s

MP 235; [all3 +304 (CHC13). (266) US- 287 13.75). 1263) NR)IR 2.45 (l'x kale). (13) MASS 562 (11-), 336, 336, 321, 168

(++, 100). (203) DEGRADATIOS: _\letal-ammonia.

(265) SOL-RCES: Anisocyc lea grandid ier i ,

Cocciilus iiirsutus, C. l a l t r i j O l i l k S , C . sar?izentosits, C. t r i lobus .

164. COCSULISISE 1267)

UT--235.5, 275 sh, 290.5. 1267) KMR TFA: 2.50-3.41 12 x NRIe):

3.68 (1 s ORle): 6.06-7.30 (9 s arom. H). (267)

Miss 578 (31-), 366, 365, 350, 183 (++I. (267)

DEGRADXTIOS : Met al-ammonia. (267)

SOURCE: Coccz~Izts pendulzis.

1%. ~ I E N I S ~ R I S E (268)

SOURCES: Coccitlzts leneba, C .

C~~H3~0eN~:590.241688 RIP 203; [a] $149 (CHCla). (217)

166. NORMENISARI~E (269) c gH&~~,:576.226038 RIP 223; [a]*' +I90 (CHC13). (269) SOURCE: Cocc~d i t s t r i lob i t s .

167. PSEUDOREPINDT-LIKE 183) C,iH3,0~N,~606.27298S RIP 168-173; [a]'* +2ZY (CHCI,).

183 ) NRIR (83) MAW GOG i l lT ) , 379, 202. (83) SOURCES: Daphiiandra dielsii, D.

specie7 unnamed.

(272) UT- 285, 350 sh. (272) NMR 2.38, 2.02 (2 s S l l e ) ; 3.58 (1 x OPIte): 3.88, 4.!4 (2 x H of bridging-CB20-); o.94 (1 s -OCH,-). (271)

51.m 020 (AI-), 379, 204, 1 i G . (271) DEGRADITIOS: Met al-ammonia.

1270)

JAS-FEB 19791 GGHA ET AL. : BISBESZYLISOQUISOLINE ALKALOIDS 67

TABLE 4. Contztiued.

SOL-RCEB: Daphnandra dielsi:, D . repaiidiila, D . tenuipes .

Type XXVI

Rt = Rt = R, = €3 P I = R3I =Me,

(7-0-me thylinsulanoline) R ,=Ei '=H 1 1 , .

BBI .1LKhLOIDS OF 172. DIXKLXEISE C36Hjs0,S2:.j9i.2i2988 1IP 285; [a; -24.4 (CHCl,). (124) SOTRCE: Stephanie diukelagei.

SOL-ECE: Bcr3e;is liiriinlaica.

SOL-RCE: Ccrnre.

U

1-R ,I '-E

l-R,l'II

ART1F;ICT ' 1-s , 1 '-s

S I ) E T E R l I I

DEGR.ID.&OS : ?\let el-ammonia. (273)

SOVRCE :

170. IKSULARIXE 1274, 275 ,

31P 157. [a]" f11.36 (EtOH). (59) UT' 200'(4.68), 229 sh (4.56), 276

K l I R 2.45, 254 ( 2 s NMe) : 3.30, 3.75, 3.82 (3 s OlIe ) . (216)

( G ) , 313 (201, 312 (loo), 311 i%) , 310 (74), 309 ( 2 6 ) , 204 (141, 190 (l?), 1i4 (191, 159 (8), 146 ( 8 ) > 140 (9). (253)

DEGRADATIOS: Metal-ammonia. 1274)

SOKF:CES: Cissanipelos ins f t lar i s , C . p i i re i ra , C y c l m z i i s i t l a r i s , Po m c y c l e n ochiaio)ia, Stephu7iio japoiiicci.

C y 1 ea inszt la r i s .

CsjH,cO& p:G20.288638

(3.64). (59)

171. S O . 16 179)

1IP 213-21i; [al'j 1156 iCHC1:).

CcsH:,O~S,C1*:636.31993S + T. t . o€ chlorine.

179 1 1 UT' 283 (3.88). 179)

KAlR 2.37, 3.30 12 ( 2 x Ol Ie ) , 3.94 12 s OhIe). 4.6

SOURCE. Cyclea p e l t a f a .

KMe): 3 7 5

(1 x -CH2C1), 5.8-T.7 (10 1 aroni. 1 H ) (59)

h-ED STRUCTURES

175. (I !-~EOCHOSDOCCR.~RISE

IIP 268 (chloride): [a!2o +I79 iH?O! (chloride). i2iG;l

SOURCE: Curare.

176. OCODENERISE

3IP 275 (chloride): [a: -170 (HzO)

~ O U R C E : -\-ecfnndrn rodiei.

177. Oroc.lwsE

Ca,H,,06Sp-- 25-lF24.319938

Ca;H,rO:T,:BOS."88fi38

ich!oride 1 . (107)

C jrHacOJ~:G08.2S8638

(chlnride'. (107) SOURCE: X e c t c i i d r n rodie i .

68 JOURKAL OF NATURAL PRODCCTS [VOL. 42, NO. 1

TABLE 4. Continlied.

178. PENDISE

blP 170-171; [a] +278 (CHCI3). (G6) SOURCE: Coccidiis penduiiis .

C3jII3~ossz:578.241588

179. PESDULIKIXE

RIP 272-273; [a] $285 (CHC13). (66) SOURCE: Coccltlirs p z d d u s .

C3jH,406~2:578.241688

183. TILIACORIDISE C39Hao0,Nz:GG4.278468 hIP 153-1515. (167) SOURCE: Tili l icora racemosa.

184. TILIANDRISE C,aH340jN2:5j0.246773 LIP 175; [a] f408 (EtOH). (74) SOURCE: Ti!iacora trinndra.

180. PROTOCHOSDOCURARIKE 135. TILI.iRTKE5 C3iH,,06S,+X-:609.301210 C?sH34OjS2:562.246773 YIP 265 (nitrate); [a]20 +l78 (H20). (2761 SOURCE: Curare. SOURCE: Tzliacora racemosa.

hlP 203-207; [CY] +283.G (hIeOH). (170)

181. PYCS.\RRIIENAbfINE C3a€Id&z :632.273383 MI' 203. (117) SOURCE: P?Ncnarrliena matiillpnsis.

182. PYCSARRHENISE

1IP 193. (117) SOURCE: Pycnurriierla m a n i l l e m i s .

CZBH~ZOYNZ :646.289033

186. TOMCSTOCURISE Cas1~,,06Nz:594.272988 MP 260; [a]'8 +202 (0.1K HC1). (5@) SOURCE: Chondrodendron toi?zentoszinz.

6Both ti1iacorir.e ( S o . 118) and tiliarine, isolated from the same source, were considered by But now the structure of tiliacorine Rao and Row (277) t o have structures of the same type.

has been modified; no work has been done on tiliarine.

TABLE 5. Names a d s y ~ o l t y ~ i z s of BBI alkaloids. (Serial number of the alkaloid (according to Table 4) is placed by the side of its name).

Aromoline 31 Atherospermoline 56

(+)-Bebeerine 132 (-)-Bebeerine 133 Belarine 93 Berbamine 57 Berbamunine 1 Berbenine 57 S, 4'-Bisnoraromoline

Cepharanoline 33 Cepharant'hine 34 Chondocurarine 129 Chondodendrine 132 Choiidrociirine 130 Chondrofoline 131 Cissampareiiie 145 CocIohine 35 Cocsoline 152 Cocsuline 153 Cocsulinine 1Gi (-)-Curine 132 (-)-Curine 133 Cuspiddine 2 Cycleacurine 134 Cycleadrine 58 Cycleahomine 59 Cycleanine 121 Cycleanorine GO Cycleapeltine 36

32

Daphnandrine 37 Daphnoline 38 Dauricine 3 Dauricinoline 4 Dauricoline 5 Daurinoline 6 1,2-Dehydromicranthine 154 Demerarine 39 7-0-Demethylpeinamine Goa T-Deme thylt enuipine 89 X-Desmethyldauricine 7 A17-Desniethylthalidezine 80 A\7-Desmethylthalistyline 16 12 '-0-Desmet hyltrilobine 155 Dihydron-arifteine 146 0,O-Dimethylcurine 13Ej Dimethyldihydron-arifteine 147 S,O-Dimethylmicranthine 156 Dimethylwarifteine 148 Dinklacorine 114 Dinklageine 172 Dirosine 19 Dryadine 104 Dryadodaphnine 105

Eferine 153 (+ )-Epist ephanine 40 (- ):Epistephanine 41 Espinidine 8 Espinine 9

J A S - F E B 19'791 GUHA E T AL. : B I S B E S Z I - L I S O Q C I S O L I S E SLKALOIDS 69

'rhBLE 5 . CO?ZtZ??Ued.

Fangchinoline 61 (*):Fangchinoline 58 Funiferine 20 Funiferine -Y-oside 21

Grisabine 10 Grisahutine 12

Hayatidine 130 Hayatinc 137 Harntinine 135 Hernandezine E l Himanthine 1i3 Honioaromolinc= 42 Honiotli*rlicrine i 2 Homotrilqbine l 5 i Hj-poepistephanine 43

Insulanoline 169 Insularine 170 Isohebeeriiie 122 (- pIsochondocurarine li4 (+)-Iqochondodendrine 122 Isofangchiiioline i 9 Isoliensiniiie 28 Isotenuipine S i Isoletrandrine 62 Isothalidezine 82 Isotiliarine 115 Isotrilobine 1.57

Krukovine 63

Lauberine 106 Liensinine 29 Limacine G4 Limacusme 44 Lindoldhamine 11

Macolidlne 44a Macoline 44b hlagnolamine 15 Magnoline 12 Menisarine 165 Menisidine 65 hlenisine 66 Methothalistyline 17 2 ' -AY-Me~h~ lberbamine 66a O-Lleth: lberbaxnine 62 411-O-Meth: lcurine 139 12'-0-Methylcurine 140 O-Meth? ldauricine 12a -\*-Meth~-l-7-O-demeth;vlpeinamine 66b Met hrldih ydroviarift eine 149 O-Meth> lisochondodendrine 121 O-lIeth> lisothalicberine 94 0-31ethj lniicranthine 158 0-Methj loxj acanthine 46 O-Meth) lrepandine 45 O-lIeth: lthalicberine 95 O-Meth\ lthalisopine 55 0-Me thvlt halme thine 96 ?rIethyl<-arifteine 150 ?\lieranthine 159 3lononiethrltetrandinium 67

Seferine 30 Semiiarine 111 (-;)-Seochondocurarjne 175 Seoprotocuridine 123 2-A\---Sorberbaniine GS (+)-Sorcj-cleanine 124 ( - )-Sore: cleanine 125 Sormenisarine 166 Z--I--Sorobamegine 69 Sorpannrensine 109 Sorrodiasine 22 (+ )-Sortenuipine 88 (- ,-Sortenuipine 89 2--\--~-ortptrandrine 70 Sorthalihrine 13 Sortiliacorine-;i 115 Kortiliacorinine-Al 116 Sortiliacorinine-B 117

Ohaberine ? G Ohsniegine i1 Ohlonganiine 47 Ocodemerine 1i6 Ocoteamine 50 Oeotine 23 Ocotosine 24-- Otocamine l i i Oroepistephanine 4 i a Oxyacanthine 48

Panurensine 110 Peinaniine 7la Pendine 178 Penduline i 2 Pendnlinine 179 Phaeantharine i 3 Phaeanthine 74 Phlebicine 25 Protochondocurarine 180 Protocuridine 126 Pseudoepist ephanine 43 Pseudorepanduline 167 Pseudotiliarine 116 Pycnamine i 5 P:-cnarrhenamine 181 Pycnarrhenine 182

Repandine 49 Repandinine 90 Repanduline 168 Rodiasine 26

Sciadenine 1 2 i Sciadoline 128 Sepeerine 50 Stebisimine 51 Stepholine 71

Telobine 160 (+)-Tenuipine 91 (-)-Tenuipine 92 (+ )-Tenuipine 90 Tet ra-0-demethglcycleanine 128a (+)-Tetrandrine i 6 (*)-Tetrandrine 77 Tetrandrine mon0-~1~-2'-oside i8

70 JOURNAL OF NATURAL PRODUCTS [VOL. 42, NO. 1

TABLE 5 . Continued

Thahadensine 106a Thalcimidine 85 Thalcimine 86 Thalfine 102

Thalibrunine 113 Thalicberine 97 Thalicrine 31 Thalicsimine 81 Thalictine 107 Thalictrimine 99 Thalictrinine 99 Thalidasine 100 Thalidezine 83 Thaligine 79 Thalieosidine 1009. Thaligosine 52a Thaligosinine 52b Thalirabine 17a Thaliracebine 14a Thalirugidine 17b Thalirugine 14b Thaliruginine 14c Thalisamine 84 Thalisopidine 53 Thalisopine 54 Thalistyline 18 Thalmethine 98

Thalmidine 95 Thalmine 108 Thalphine 102 Thalphinine 103 Thalrugosamine 52 Thalrugosaminine 55 Thalrugosidine 101 Thalrugosine 79 Thalsimidine 85 Thalsimine 86 Tiliacoridine 183 Tiliacorine 118 Tiliacorinine 119 Tiliafunimine 79a Tiliageine 27 Tiliamosine 120 Tiliandrine 184 Tiliarine 185 Tomentorurine 186 Toxicoferine 141 Tricordatine 161 Trigilletimine 162 Trigilletine 153 Trilobamine 38 Trilobine 163 (+)-Tubocurarine 142 (-)-Tubocurarine 143 (+)-Tubocurine 130 (+)-Tubocurine 144

Warifteine 151

TABLE 6. Calculated molrcular weights of BBI a l k a l q d s . (Serial number of the alkaloid (according to Tablo 4) is placed by the side ol its name).

546.215473 :CaaHsoOsNs 568.257338:C34f-I360sNs 1,P-Dehydromicranthine 154 Lindoldhamine 11

548.231123:C34H320j?r~2 576.226038tC3jH3206N2 Cocsoline 152 Normenisarine 166 12'-0-Desmethyltrilobine 155 RIicranthine 159 576.262423 :C36H360sNz Tricordatine 161 Dinklacorine 114

550.246773 :C34H3405S2 Tiliacorinine 119 Tiliandrine 184 N,O-Dimethylmicranthine 156

Isotrilobine 157

Trigilletimine 162 578.241688:C3sH3,0,N, Cocsulinine 164

Xortiliacor~ne-il 115 Pendulinine 179 Kortiliacorinine-A 116 Nortiliacorinine-B 117 580 257338:C35H3606Sz Cosuline 153 Daphnoline 38 0-Methylmicranthine 158 7-0-demethylpeinamine 60a Telobine 160 2-N-Sorobamegine 69 Trilobine 163 Cycleacurine 134 Tiliarine 185

566.24 1688 : C 34H3406N z Stebisimine 51 N , SI-Bisnoraromoline 32 Sciadoline 128 Tetra-0-demethylcycleanine 128a Menisarine 165

Tiliacorine 118

558.215473 :C3jHmOsS2

562.246773 :CajHaaOsNz Pendine l i 8

590.241688:C3sH3a06Sz

JAS-FEB 19i91 GCHA ET AL. : BI~BESZTLISOQUSIOLISE ALKALOID^ 71

TIBLE 6. Cont inued .

Cepharanoline 33 Hypoepistephanine 43 Tiliafunimine 79a Thalmethine 98 Tiliamcisine 120 Rarifteine 151

594.272988 :C 85H 310 gN 2

.Iromoline 31 Daphnandrine 37 Denierarine 39 Nacolidine 44a Sepeerine 50 Atherospermoline 56 Krukovine 63 L\7-Methyl,7-0-demethylpeinamine 66h 2-S-Sorberbamine 68 Obamegine 71 Peinamine 71a Dryadodaphnine 105 Thalhadensine 106a Sorpanurensine 109 Isochondodendrine 122 Xeoprotocuridine 123 Protocuridine 126 Chondrocurine 130 (+)-Curine 132 (- )-Curine 133 Hayatine 137 Toxicof'erine 141 (-)-Tuhocurine 144 Dihydrowarifteine 146 Dinklageine, 172 Tomenrocurine 186

596.288638:C35HaoOgrz Berhamunine 1 Dauricoline 5 Espinine 9 Magnoline 12

606.27298a:C3;H3j061;2 Ocotosine 24 Cepharanthine 34 Coclobine 35 (+)-Epistephanine 40 (- )-Epistephanine 41 0-1Iethylthalmethine 96 Cissampareine 145 Nethyln-arifteine 150 Pseudorepanduline 167 Insulanoline 169

608.2886381C 3,HtsO&;, Sor-rodiasine 22 Ocotine 23 Phlehicine 25 Tiliageine 27 Cycleapeltine 36 Homoaromoline 42 Liniacusine 44 Macoline 44h Osyacmthine 48 Repandine 49 Thalrugosamine 52

Berbamine 57 Cycleadrine 58 Cycleanorine 60 Fangchinoline 61 (* ) -Fangchinoline 58 Liniacine 64 Menisidine G5 2-Sortetrandrine 70 Penduline 72, - Pycnamine (0 Thalrugosine 79 Belarine 93 Thalicherine 97 Dr>-adine 104 Lauherine 106 Thalictine 107 Thalmine 108 Panurensine 110 Kemuarine 111 (+)-Sorcycleanine 124 (- )-Korcycleanine 125 Gciadenine 127 Chondorfoline 131 Hayatidine 136 Hayatinine 138 4"-O-Methylcurine 139 12-0-Methylcurine , 140 Methyldihydromwifteine 149 Himanthine 173 Ocodemerine 176 Otocamine 177

(+)-Tubocurarine 142 (-)-Tubocurarine 143 Protochondrocurarine 180

CusDidaline 2

609.304210 :C3:HalObT2

610.304288:C37Hi~O~~;2

Dairicinoline 4 Daiirinoline 6 S'-Desmethyldauricine 7 Esvinidine 8 GGsabine 10 Sorthalibrine 13 Dirosine 19 Isoliensinine 28 Liensinine 29

616.257339:C8.H36Osl1'2 Phaeantharine 73

620.252253 :C3;H3&0;?j2 Osoepistephanine 4ia Repanduline 168

Dimethylwarifteine 148 Insularine 170

620.288638:C3jHaoOsS;2

622.267903 :C 3iH350 ;S2 Thalsimidine 85 (+ )-yortenuipjne 88 (-)-\ortenuipine 89

622.301288:C3sH1zOsS? Funiferine 20

7 2 JOURNAL OF NATURAL PRODUCTS [VOL. 42, so. 1

TABLE 6. Continued.

Rodiasine 26 0-Methylrepandine 45 Obaberine 16 Isotetrandine 62 llenisine 66 Phaeanthine 74 i+ 1-Tetrandrino 70 (+)-Tetrandrine 77 0-1\Iethylisothalicberine 94 U-Jleth, lthalicberine 95 CT cleanine 121 0. &Dime t hrlcurine 135 DimethyldiGydrox-arifteine 147

623.312113 :C3cH4306K2 Oblongamine 47 2-S'-Methylberbamine 6%

Thalisopidine 63 -\--Desmethj-lthalidezine 80 Thaligosidine l0Oa

624.319938 : C ~ S H , ~ O ~ N Z Dauricine 3 Thalibrine 14 Neferine 30 Chondocurarine 129 (-)-Isochondocurarine 174 (+)-Seochondocurarine 175

hlagnolamine 15

632.2?3383:C35H400gSz Pycnarrhenamine 181

Thalsimine 86 Isotenuipine 87 Repandinine 90 (+)-Tenuipine 91 (-)-Tenuipine 92

626.299203 :CaiH:zO;K?

636.283553 :C3~H400iNz

637.327763 : C ~ ~ H : S O ~ N Z Cj-cleahomine 59

Funiferine ,V-oxide 21 Thaligosine 52a Thaligosinine 52b

638.299203:C3iH4zOiSz

Thalisopine 54 Isothalidezine 82 Tetrandrine mono-rV-2'-oxide i 8 Thalidezine 83 Thalisamine 81 Thalfoetidine 99 Thalrugosidine 101

0-Met h>-ldauricine 12a Monomethyltetrandrinium 67

Thalirugine 14b

Pycnarrhenine 182

638.335688:C3eH,60sNz

64-0.311853:C38H?40i~~

646.289033 :C~6H4zOqNz

G18.217168:C3sH360sSz Thalfine 102

G52.278468:C3sH,cOsNz Thalibrunimine 112

Thaliracebine 14-a Thalrugosaminine 53 Hernandezine 81 Thalidasine 100

Thaliruginine 14c

661.2784G8:C3sH,cOsSz Tiliacoridine 183

Thalfinine 103

668.309768:CasH440iNz Thalibrunine 113

Thalirugidine l i b

N-Desmethylthalistyline 16

Thalirabine l i a

652.311863 :C3sH,,O;Kz

654.330503 :CgsH,rOiNz

666.294118:C~~K~zOsN~z

670.325418:C38H,,OsS2

682.325418 : C ~ O H : S O E ~ ~ J ~

683.333243 :C40H:i0&;2

697.348893 : C ~ I H ~ ~ O ~ N Z Thalistyline 18

712.372368:C,~Hj~OsN~ blethothalistyline 17

France, for useful information. The Calcutta group wishes to thank the University Grants Commission, S e w Delhi, and RM is indebted to the CKPq, Rio de Janeiro, Brasil, for re- search grants. The co-operation and facilities received from Dr. S. Sikdar; Head of the*De- partment of Pharmacology, Calcutta University, and the authorities of K. K. College, Ber- hampur, W. Bengal, are gratefully acknowledged.

Receieed 23 M a y 1978.

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03

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88.

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BICK, I . R . C. and T. G. WH Y . 1946. A\lkaloids of Queensland flora. I. Alkaloids of Dapi im?idra repnndirla. 1 QyeeiLsliznd P a p e r s , D e n t . Clieni. l (28 ) : 8 ; Cheni. A b s t r . 41: 1390a (1947). BICI~, I . R. C. and IT. I. TAYLOR. 19i l . Alkaloids of Dapliiinndra species. Part X. The structure of isotenuipine. BICI~, I. R. C., J. HARLEY-X~SOS and3I. J . 1-ERSESGO. 1963. The structure of tenuipine, nortenuipine and repandinine. BICIC, I . R . C., G. K. DOUGLAS and R. I . T-LYLOR. 1969. Alkaloids of Dryadodaphne nocogziineensis. DEBRAT, ll., hl . PLAT and J . L. h1.1~. 1966. Alkaloids from African RIenispermaceae: Epineiriiiiz cordifoliiiiii and Epinetriini nraiigenotii, isolation of cycleanine, norcycleanine and isochondrodendrine.

J . Org. Client. 38: 1846-1852.

1975: 2219-2220.

J . Ciieni. Soc. C 1971: 3779-3783.

d n n l e s Asoc. Oiri i i i . A r g . 5: 135-147.

J . Chein. Soc. C 1969: 1627-1632.

A m . Phariir. Fr. 24: 551-558; Chenz. A b s t r . 66: 2 8 9 4 2 ~ (1967). 88a. BOUQUET, A. and A. CIT-E. 1971. Epine trzwi ;#il!oszmz. Plant M e d . Phytotirer. 5 ( 2 ) :

131-133; Chelir. A b s t r . 7.5: 85207 u (1971). 89. GALEFFI, C., G. B. X~.RINI-BETTOLO and D. 1-ECCHI. 1975. (R,R) (-,-)-12'-0-1lethyl-

curine and (R,R) (-,-)-O,O-dimethylcurine, tFo new natural alkaloids from Guatteria megalophyi ln Diels.

90. R~TT-, L. R . and A. S. R. ANJANEYULU. 1962. The alkaloids of Gyrocarpi is jacqirini Roxb.

90a. GUPTA, B. D., S. K. BANERJEE and K. L. HASDL 1976. Alkaloids and Coumarins of Heracleuwz sal l ichi . Phytochenzistry 15: 576.

90b. HOCQUEniILLER, R., P. C.IBALION, A. BOUQUET and 8. C a v ~ . 1977. Isopiline, a new aporphine alkaloid from Isolona pilosa Diels, hnonaceae . C. R. Aced. Sci. S e r . C.

Gazz. Chinz. Ital. 105: 1207-1213.

J . Sci. Ind. Res. (India) 21B: 581-582.

285 114): 447-43. 91.

92,

93,

94.

95.

96.

97.

98.

99.

100.

101.

BIISCHI, E., J. A. G.IRB\RINO and F. GIORA. Gazz. Chim. Ital. 92: 818-822; Chem. A b s t r . 58: 4614c (1963).

1962. Lazirelie semperoirens alkaloids.

TOMITA, M., H. FURVICATYA and K. FUK.IG.ITT-.L 1967. Alkaloids of menispermaceous plants. CCXXXI. Alkaloids of Liiiiacia cuspidata. 1. The structure of limacine, liniaciisine and cuspidaline, new phenolic bisbenzylisoquinoline bases. Yakzigaku Zassiii 87: 793-796. Tonm.i., AI., M. JCICHI and II. FURCKATYA. 1967. Alkaloids of menispermaceous plants. CCXL\?I. Alkaloids of Limacio oblonga. Yakiigakii Zassiii 87: 1560-1561; C h e m . A b s t r . 68: 84980j (1968). LE, S. T. and I. S. CHEN. Structure of a new bisbenzylisoquinoline alkaloid, lindoldhamine. Heterocycles 4: 1073-1076. ITO, K. 1960. Alkaloids of magnoliaceous plants. XXIT-. Alkaloids of iMiciielia conzpressa. CHATERJEE, R . and 11. P. GUHA. 1949. The alkaloids of Mahonia acanf l iqol ia , Sci. end Cziltiire 15: 163; Chem. A b s f r . 44: 270Ge (1950). Pan-or, P . P. , N . 31. ~IOLLOT and L. N . P ~ s o v a . Alkaloids from plants of the Berberidaceae family. D o k l . Bolg. A k a d . A7aztk 24: 675678; Chenz. Abstr . 75: 1484652 (1971). CHATTERJEE, R . , 11. P. GVHA and S. K. SEN. 1950. Studies on ~lfaaiionie genus. 111. Mehonia borealis and ?daiionia sw ions i i .

1976.

Yaki igeku Zassiii 80: 705-707; Cheni. A b s t r . 54: 18887e (1960).

1971.

J . Ani. Phernt. Assoc. 40: 36-39. CHATERJEE, R . and If. P. G~HI. 19.50. Studies on Mahonia genus. I. The alkaloids

CHATERJEE, R . and hl. P. GUHL 1951. Jfahonia genus. IT-. -TI. leschenaulfzz, X. nzanzpztrenszs and JI. s~kkzwienszs . J . Ani. Pharrn. Assoc. 40: 229-232. YISG, T. H. 1960. Alkaloids of Berberidaceae. XXIX. Alkaloids of Mahonza lornarzfolia and JI. morrisone)iszs. Yakicgaku Zassht 80: 1304-1307; Cheni. A b s t r . 55: 3005h (1961).

of JI. gr t f i th l . J . A v ~ . PhUr???. ASSOC. 39: 181-182.

-- JAS-FEB 19791 GCHA ET AL. : BISBESZTLISOQUIXOLISE ALKALOIDS ii

102.

103.

104.

105.

106.

107.

108.

109.

110.

111.

l l l a

112.

113.

114.

115.

116.

117.

118.

119.

120.

121.

122.

123.

124.

125.

1%.

126s 127.

AGL-ILIR-SASTOS, G. and S. T-ILLAREAL. 1961. Tertiary alkaloids of two Philippine Berberidaceae. P r o c . Syiiip. Pligtoclieiir. 1-nic. Hongkoiig 1961: 48-50: Cheni. Abstr. 61: 16442d (1964). D O ~ I ~ O T C H , R. W. and J . E. KSAPP. 1971. -1lkaloids from 3lenisperniztnz c a m d e n s e . L lo j t l iu 34: 292-300. TOJITTA, 11.. I-. Oh.woTo, I-. S.IG.LT, K. Ku.ii-.iii.~ and H. T.is.\~an-.i. 1970. Studies on the alkaloids of menispermaceous plants. CCLT-11. hlkaloids of Xetiisperii i icni daitricuni DC. (Suppl. 5). The structure of a nen tertiary phenolic biscoclaurine ripe alkaloid “Dauricoline“. I a k i t g a k u Zasslii 90: 1178-1181. TOMIT.\! A l . , Y. OK.ivoTo, T. SAG.LI, S. T.is~1c.i and T . H.LYATA. 1970. Studies on the alkaloids of menispermaceous plants. CCLTTII. -1lkaloids of J~ei~isperit i12z1))z daz t r i c i tm DC. (Suppl. 6,. Basic components of Siberian X e u i s p e r i i i i o i > daitricitvi DC. (Lztilo- s e i i i j e n ~ i k d o u r s k i i ) . CH-IS, I(. C.. 11. T. -1. ET-.ISS. C. H. H.~ss.~L and -1. 11. K. SISGSTER. 1967. Bio-

Ihkicgaku Zasshi 90: 1182-1186.

synthesis or’ phenols. Structural relationships of alkaloids of Demerara greenheart. HEARST, P. J. 1964. Greenheart alkaloids. 11. Isolation and characterisation of seven alkaloids. J . O r g . Ciieni. 29: 468-470. TOJIIT.~, 31.; H. FURUKAII-A, T . H. ~ L S G and T. J. LIX. 1964. Studies on the alkaloids of Loti embryo. (1). Structure of isoliesinine. Tetrahedron h i t . 1964: 2637-2642. CH-IO, I-.: I-. CHOU, P . TASG and C. CHOU. Alkaloids of embryo Se i i t r i i bo t iuci- f era . 1. Isolation and characterization of liensinine. S c i . S in ica (Pekiiig) 11: 215-219; Cheni. A b s f r . 57: 7363i (1962). FuRx~IT-.~, H. 1965. Alkaloids of S e l i t m b o ~ i t c < f e r c l . X. dlkaloids of Loti embryo. 1. Ilomestic S e l i t i i i b o nitcifera. I-ukiigakii Zasslii 85: 353-3541 Clieiii. A b s t r . 63: 435ld (1965). BICK, I. R . C., H. 31. LEOIT-, S . IT. PRESTOS and J . J . TRIGHT. 1973. Alkaloids of S e m n e r o n cieil lerdii (Moniniiaceae). HART: S . K.: S. R . .JOSES, J . h. LUIBEETOS and H . RES. 1972. -1lkaloids of PachJgone p i tbescois illenisperniaceae 1 . TO\IiT.I, ll., H. FERELIII-.~, 11. JUICHI and S. L r . 1967. l lkaloids of menispermaceow plan-s. CCSLT-I. Alkaloids of Parncjc lea och ia iam. I-trkugakit Zasshi 87: 1255-1287; CIieiii. .i b s f r . 68: 4 6 7 6 k - I1968 I .

Part S I I I . J . Cliem. SOC. C 1967: 2479-2485.

1962.

d z t s t r n l i m J . Cireiii. 26: 455-459.

-4 i tsi . J . Ciieiii. 25 10) : 2289-2290.

\ - - - - I ~~ .. ..

BRL-CHH.~ESES, F. I-., A. C. S-~STOS, J. KSABE and G. A. S.~STOS. 1957. The structure of phaentharin. SASTOS, A. C. 1931. hlkaloids of Piieeoufiiits ebrac feo la fus iPresl) AIerrill. Phaeanthine

-4 rcli. Pliariii. 290: 232-250.

I. -$SET, F. -1. L., G. K. HUGHES and E. RITCHIE. The alkaloids of P l e o g y i e cun- tiiiigliniitii. SIDUMIS! -1. -1. and 1’. S . T ~ H I S T . 1972. S e x hisbenzylisoquinoline a!kaloids from Pjcmrrt’ienii 0 i~s fr !1 / iam7 (llenispermaceae j . BRL-CHH-~L-SES, F. T-., G. -1. S.LSTOS and C. SCHKFER. 1969. .Ilkaloids from P ~ c n o r r l i e n a mzni/!sji.yis T-idal. Pycnaniine, 5 nen- biscoclaurine alkaloid - E the brrhaniine series. d rcii. Pharnz . 293: 454-461. LODER, J. W. and R. H. SE.~RS. 1972. Tumor inhibitory plants. Tn-o new bis- benzylisoqiiinoline alkaloids from Pyni i rr l ien , z oznnihn (3lenisperniaceae). d u s i r ‘ l h t t J . C5eiu. 25: 2193-2197. T.KIH.~SHI, K., 11. J. MITCHELL and 11. P. C a n . 1976. Sciadenine, a nev bisbenzyliso- quin,Aine alkaloid from Sciadoteiiio tosirere. T-IILIHISHI! K. and 11. P . C.i\-.i. Sciadoline, a nen- type of bisbenzylisoquinoline alkaloid. HeierocFcles 5( l ) : 367-371. Tox1T.i. 31. and H. SHIRII. 1942. ;ilkaloids of menisperniaceae. LIT-. Alkaloids of S i e p h n i a capi fa tn . TAS.II<.\, K. 1941. Alkaloids of llenispermaceae. LST-111. Structure of epistephanine, the alkaloids of Steplinizie capiin!a. J . Phnrii i . Soc. J a p a n 61: 27-35; Clieiiz. A b s t r . 45: 5173d (195lj. Toim.i, 11.. T. S.Y\V.~D.I> 11. 1iozric.i; 11. T.KEUCHI and 11. A 1 ~ c . \ ~ r . 1969. Alkaloids of nienisperniaceous plants. CCLI. -1lkaloids of Steplintzia cephaianfha . 8 . Alkaloids of S i e p h e n i o cepiialeiztih cultivated in Japan. P I R I S , R. .I. and J . LE JfES. 1955. .S!ephania dinkeliigei (llenispermaceae). i l i z n . Pliarin. F r . 13: 203-204: Clieii s f r . 49: 11959e (1959). KUPCH-IS, S. ll., IT. L. ASB nd B. S. THY.\G.~RIJ.\S, 1961. llenispermaceae alka- loids. 111. -1lkaloids of Si iia h e r m n d i f o l i n . J . Piiarm. Sci. 50: 819-822. T o ~ T . ~ , 11. and S. UED.I. 1959. -1lkaloids of menispermaceous plants. CLXXIT-. Alkaloids of Indian drug x-hich originates from Sfepiianie herizandifolia. Y u k i ~ g e k u Zasshi Ref. Ga. p. 2T9. T O ~ ~ I T . ~ , 11. and T. IBUK.~. 1963. .Ilkaloids of menispermaceow plants. CCIII . Alkaloids of formosan Stephnniil j apon ica . 1. Isolation of tertiary bases. I’akugaku Zasshi 83: 996-999; Chenz. A b s i r . 60: 4201h (1964).

Re;!’. Filipine M e d . FariiL. 22: 11: Cheiii. d b s i r . 26: 729 11932). ’ 1950.

ilusfrelietz J . Sci. Research 3.4: 346-3491 Chem. A b s f r . 45: 822i (1951).

.iustrriiinn J . Chem. 25: 2251-2254.

H e f e r o c j c l e s 4: 471-474. 1976.

J . Pliariii. Soc. J a p a n 62: 351-386: Chew. . Ibsfr . 45: S540e (1951).

I’akugnku Ziissiii 89: 1678-1681.

78

128.

129.

130.

131.

132.

133.

134.

135.

136.

137.

138.

139.

140.

141.

142.

143.

144.

JOCRXAL OF SATURAL PRODUCTS [VOL. 42, NO. 1

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2 .

1967.

1968.

23: 2887-2892.

Structure of thalisopine.

1970

\- --, 144a. LIAO, TT-TT,JT L. BE.\L, W-S. WL- and R . 1%’. DOSKOTCH. 1978. Alkaloids of Tlmlictrztm

XXT-I. Lloydia 41(3): 25i-270.

145. WALI, B. K., S-. P . A ~ L and K. L. HASDL 1964. -4lkaloidal constituents of Thalictrunz p e d i ~ i i c ~ t l e t i t n ~ EdgeT.

146. WU, TV-X., J. L. BEAL, R-P. LEU and R . W. DOSKOTCH. 1977. Alkaloids of Tl ia l ic t rum. XXI. Isolation and characterisation of alkaloids from the roots of Thalic!ritm podo- curpi im. L loydia 40: 384-394.

147. SHAMMA, 11. and S. T. TAO. 1973. Thaligine, a ne-- bisbenzylisoquinoline alkaloid from Tiiil!ic!ririii polyguiii irm Nuhl. (Ranunculaceae).

148. Rr, W-S. , ,J. L. BE.IL and R . W. DOSKOICH. 1977. Alkaloids of,Thalictrzrm. XXII . Isolation of alkaloids with hJ-potensive and antimicrobial activity from T’iialictrztm rerolzttztiii. L loydin 40: 508-514.

149. FOKG,, H. H. S., J. L. BEAL and 31. P. CAT-A. 196G. Alkaloids of Tlinlictrmi. 1-11, Isolation of alkaloids from the roots of Tiielictrtini rociiebrzrnian~tni. Lloydia 29: 94-100.

150. Sa.i, J. RI . , A I . J . MITCHELL, 11. P. Cava and J . L. BESL. 1976. Thalibrine and nor- thalibrine, new bisbenzj-lisoquinoline alkaloids from Tiialic!rirm rociiebr~tnia?ili l)~.

S e w hypotensive and other alkaloids from Thal ic t runi ?iiiiizts Race B.

Indim J . Pharn i . 26: 69.

Exper i ev i ia 29: 517-518.

Heterocyc’es 4: 753-757. SA.\, J . 31., 11. I-. L~I;SH\lIK.\STHA\I, hI. J. ~IITCHELL, AI. P. Cars and J. L. BEAL. Thalibrunimine. a nex iminobisbenz\ lisoauinoline alkaloid.

151. 197G. Conformers of thalsimine. ” _

Tetra l iedro?~ Let;. 1956: 513-516.

JAS-FEB 19791 GTHA ET AL. : BISBESZI~LIYOQUISOLISE ALKSLOIDS i 9

152.

152a

153.

154.

155.

156.

157.

l5 ia

158.

159.

160.

161.

162.

163.

164.

165.

166.

l6Fa

~IITSCHER. L. -4.. W-S. Wu. R . W. DOSPLOTCH and J . L. BEAL. 1972. Antimicrobial agents f r o b higher plants I1 .’ Alkaloids from Thuiictrunz ricgositnt. Wr, W-S.. J. L. BEIL, E. H. FAIRCHILD and R . W. DOSXOTCH.

L l o j d i n 35: 167-1?6. 1978. Six new bls-

benzylisoquinoline alkaloids from Thalictrunz rugosicni. NITSCHER, L. .4., W-X. IVv and J. L. BEAL. Thalictrunz rugosum. Myc-o bncteriu ni smegma tis , E x p e r ien tie 28 : 500. Wu, W-S., ,J. L. BE-IL, G . W. CL.IRK and L. A. MITSCHER. from higher plants.

J . Org . Chem. 43: 580-585. 1972. -4ntibiotics from higher plants.

Thalrugosamine, a nen- bisbenzylisoquinoline alkaloid active W.

1976. Antimicrobial agents ddditiona! alkaloids and antimicrobial agents from Thelictr~m

r i r g o s i c i n ~ L l o j d i n 39: 65-75, ?IIOLLOV, S . AI. and I-. ST. GEORGIET. Secondary alkaloids of Thalictricm s imp lex L. MAEI\H. S. KH.. Z . F . I ~ M ~ I L O V and 8. Yu. I-L-ST-SOT-. 1968. Thalsimidine. a ne--

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