BISBENZYLIS0QT;INOLINE ALKALOIDS--A
REVIEW
K. P. GUHAand B. MCKHERJEE D e p a r t m e n t of Piiarmacologg, B . C. R o y P o s t Graduate I n s t i t u t e of B a s i c Jfedical Sciences, 244B, d c i i a r y a J . C. Bose R o a d , Calcutta-700 020, I n d i a and
R . MUKHERJEE Fiicitldade de Farmacia, L-ni;.ersidade Federal d o Rio Grande d o Sztl, Porio .4legre, RS,Brasil
.$BSTR.xT.-The review presents a glossary of the bisbenzylisoquinoline a k a loids. The following information is tahulated: structural formulas of all the bisbenzj-lisoquinoline alkaloids (BBI) with their molecular formulas: molecular n-eights: mp and : a ] values: ~ uv, ord, nnir, mass data: degradation methods applied to determine 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 differenf 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, Bebeeriiim pirrum and Curare (the arron- poison of South A%mericanIndians), natural products chemists and pharmacognosists have been interested in the bisbenzylisoquinoline (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- B B I alkaloid-. The present report ainis to fulfill this demand. BBI alkaloids are built up of tn-o benzylisoquinoline (BI) units linked by ether bridges. I n 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 osygenated 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 r 3 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 ( S o . 1 3 i , table 4) and hayatinine ( S o . 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).
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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 t o 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*
6,7,10*,12,13-6,7,12*
I
G,7,11*,12-5,6,7,12*
I1
5,G,i,11*,12-5,6,7,12*
b. Head t o head
c.
Ia
111
Head to tail A
R;
R2-
RI
G,i,8*,12-6,7*,12(11-11) IV
B.
G,i,11*,12-6,7*,12
V
TKO DIPHENYL ETHER LINKAGES.
a. Head to head and tail to tail
Bod G , i * ,11t, 1 2 4 , i ,8*, 12t VI
5,G,7,8*,12j-S,i*,llt,12 VI1
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6,7,S*,llt,l2-G,i*,12t \I11
3
ALKALOIDS
5,GJ7,S*,lli,l2-G,7*,12t IX
0-RG
c,i,8*,lltJl2,l3-G,7*,12t X
G,7,S* ,1 1 t ,12-G* ,7,12t X I
5*,6,i,11t,12-5,G,iJS*,12t
XI11
5,6,7,8*,10~,11,12-6,i*,12~ XV11 b. Only head t o head
tLqg 6,i",8i,12-6*,it,12(11-11~
SVIII
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c. Head t o tail
' ' l ; % & \ {
' 0-n5Rkr0 G,7,8*,12t-G,7,8tJ12*
c.
OSE D I P H E S T L
H-
R;
'
G,7,8* ,11t ,12-6,7t, 12* XX I
XX
ETHER . i X D O X E B E S Z T L PHENYL ETHER
G,iJ8*,12*-G,7,8*[7-12]
/
LIN1i.IGES.
XXII
D. THREE D I P H E S Y L ETHER LISKAGES.
E.
T W O D I P H E S Y L ETHER . I S D ONE PHENYL-BENZYL ETHER LINKAGES.
Rl-N Rl
CHi
G,7,8*,llt,12,13-6,7*,12t[8-6]XXV
G,7,8*,12t-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 t o tail coupling, the more highly oxygenated benzylisoquinoline 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 parentheses, 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 ( S o . 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
JAN-FEB
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GUH.4 ET AL.
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BISBENZYLISOQUIKOLIXE 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 . fortuiiei (Hort.) Fedde, was found to contain oxyacanthine (15). Stephaizia rotunda 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 ( S o . 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 Mahoriia fortuiiei Fedde, the trunk is found to contain berbamine ( S o . 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 solution. Hot alcohol extraction x a s done by Boissier (11). 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). I h p c h a n (58) used 1.5% triethylamine in methanol. and Cava (21) used aqueous ammonia-ether for the extraction of Cissampelos pareira and -4bufa 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. I h p c h a n ( i 9 ) has also used heptane and toluene. I n several cases (lo), the p H 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 p H 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
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TABLE 2. Distribution of tile different groups of bisbenzylisoquinoline aLka!oids in different genera. ~
No. of B B I alkaloids obtained Family
Genus
s o . of ,peciee tudiec
I
IV
VI
v111
Aristolochiaceae Anonaceae... .
Berberidaceae Buxaceae Hernandiaceae Lauraceae Magnoliaceae Menispermaceae
Monimisceae
h-ymphaceae Ranunculaceae Rbtlmnaceae Umbelllierae
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
1 1
1
1 1 1
1 21 13
1
3 1
3
3 2
1
1 1
2 1
5
1
2 4 1
1
2
2
1
1 4 2
4
3 2
2 13
1
1
1
fi
fi
6 3 5 3
1
5 4 6 5 3 2 2
1 5
1 1 1
3 1
8 4 3 1 8 1
3 2 5
1
1 1
1
li1 2
G
1
1 1
1
2 1
-
4 1 1
-
chromatography were first made by Tomita and Watanabe (177) using paper pretreated with buffer of p H 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 t o descending paper chromatography 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
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E T AL.
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BISBEKZYLISOQUISOLISE ALKALOIDS
TABLE 2. Distribution oj' the different ~ r o u p soj' bisben~Tlisoquinolinealkaloids i n different genera. S o . of BBI alkaloids obtained 1
XV I
YVI I
YVIII
-XI" xV
YXlI
XIX
1
-
~
mined
1 1
2
1
1 !
1 !
1
2
1
2
1
1
3 2
8
3 3
3
2
1
1
1
1 5
1
,
2
3
2 2 2
6
3
1
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 butanolacetic acid-water of varying proportions. The spots were detected by spraying the dried paper first n-ith the potassium salt of tetrabromophenolphthalein ethyl and then TT-itli an aqueous solution (0.05%) of oxalic acid. ester (@.IT) Thin layer chromatography i- more ividely used to aqcay the alkaloidal mixture, Dopke (150) employed silica gel plates prepared n i t h 0.1 S Sodium hydroxide to ceparate the compound< of greater ba.icity. phaeanthine. i-otetrandrine, pycnamine. berbamine and oxyacanthine. B o i 4 e r ( 1 i 3 ) u-ed this method for
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TABLE 3. Botanical sources of bisbenzylisoqiLinoline alkaloids. (Serial No., according t o Table 4, of the alkaloid is placed by the side of its name). Plant part studied
S a m e of the plant Abufa cnndicans Rich ex nC.. ......... (Chondodendron candisans Sandaitli) 4 . grisebachii Triana and Planchon
. . . . . .
4 . panurensis Eichl..
Stem Stem
Stem Stem
A . splendida Krukoff and Moldenke
......
Stem
d ~ o m o s p e r m i r mprandifolium Eichl. . . Aristolochia Indica Linn. . . . . . . . . . . . . dtherosperma moschatum Labill.. . . . . . .
Stem Root Leaf Bark
A . repanddum F. Muell.. . . . . . . . Berberis amicrensis Rupr.. . . . . . .
See Daphiiavdri Stem
B. aquifolium Pursch. .
Root
.-inisoc>clea gradidini H. Bn..
.
.
.
.
.
B . drislata DC.. . . . . . . . . . . . . . . . B. asiatica Rosb. ex DC.. . . . B. ,floribunda \Tall. ex Don. ........ B. (aristafa) B..fortunei Lindl.. . . . . . . B. heteropoda Schrenk B . himalaica Ahrendt . . . . B. inlegerrima . . . . . . . . . . . . . . . . . . . .
See Berberi. Root, bark stem Root See .Ifahonti See Berber! Stem-bark Leaf
B. japonica R. Br. . . . . . . . . . . . . Berberis julianae Schneid. . . . . . .
Root
B. kawakamii Hayata
Root
B. lambertii R. S . Parker
Root
B . laurina (Thunb.) Billb.. . . . . . . . . . .
Root-bark
See Jfahonzr
Trunk-bark and root B. lycium Royle . . . . . . . . . B. mingelsensis Hayata . . . . . . . . . . . . . . . . . Root B . morrisonemis Hayata . . . . . . . .
B. oblongn. . . . . . . .
..........
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 66b (Pia) 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 62 (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) ethyl berbamine 66a (42a) Oblongamine 47 (42) 0x3-acanthine 48 (42)
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 vI
Cndetermined
I VI
VI11 VI VIII VIII VIII VI XI I
I XIV XI VI VI11 VI11 YIII
r111 VIII I VI11 VI VI
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BISBESZYLISOQUINOLINE ALKALOIDS TABLE
3. Continued. II
S a m e of the plant
Plant part studied
B. petiolaris Sal1 B. svaseyr Bucke) (Mahonia s b u s q i Fedde) B. thunbergri DC B . tinitoria Leschen. . ( B . aristda) B. lschonoskyana Regel
.
Berbamine 5; 112b) Berbamine 5i (43)
VI11 VI11
Whole plant
Berbamine 5 i (44) Isotetrandrine 62 (44) Oxyacanthine 48 (44) Berbamine 5 i ,331
VI11 VI11 VI VI11
Obaherine 46 (45) Obamegine i l 14.5) Ox;\-acanthine 48 (45) Berbamine 5 i (46) Osyacanthine 48 (47) Berbamine 5 ; 4 i a j (')-Curine 132 (48)
VI VI11 VI VI11
Stem
Root I
1
*
Leaf See d b u l a
Root Leaf Stem, root and leaf Root and leaf Stem and barb
Cissampelos iiisnloris JIakino . . iParacgclea ivsularis Maliinol Kudo and Yamamoto] C. mucronafa d Rich C ocalifolia DC
Stem and leaf Stem
,
Root
I
C . japonicirs DC.. C. laurifoliirs DC.
xx XXI XXI
xx XXI XXI XXI
xx xx XXI xx XXI
L-ndetermined
XXI
xx XXI xx
Cissampareine 145 i 5 S ) Insularine l i 0 (59) Isochondodendrine 122 (11, 59) 4"-O-\Ie:hylcurine 139 (60) Root and leaf (-]-Curine 133 110, 11, 60, 61) C;\-cleanine 121 f59, 6 1 ) Ha>-atidine 136 (61) Hayatine 137 (IO. 11, 61) I Ha-atinine 136 110,A l l , Stem and root Isotrilohine 15; '62) Trilohine 163 (62) See .Siefihania jagoiiica 'Thunh.) Miers Bark and trunk 1 Isotrilobine 15; '63) Trilohine 163 (63)
1
1
Whole plant Root
"
Cocculus hirsxtus (Linn.) Diels
XXI
Insularine l i 0 5 5 ) Isochondodendrine 122 (56) Dih5-dron-arifteine 146 1 5 i )
Root
Dimethyldihydron-arifteine 147 Dimethl-lwarifteine 168 (57) JIethyldihydrorrarifteine 149 ( 5 i ) Jleth>-lnarifteine I50 ( 5 i ) Warifteine 151 (57)
C . pareira Linn
xx xx
Isochondodendrine 122 (20) Chondocurarine 129 (51) 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 )
Stem
C. toxicojmiim ' n ' e d d . ~Kruk. et Mold
XXI
Sandwith Isochondodendrine 122 (49) i+1-Sore,-cleanine 124 (49, 50) ibaee B) (+ -Curine 132 (20) Isochcndodendrine I22 1 0 ) Chondroioline 131 '20) (-)-Curine 133 (20)
)
C . tomeiitosiim Ruiz and Pavon
\' I
VI11
caiidicans
Wood
C. miirofih:.lum (Eichl. 1 Moldenke. . . .
iS~chnosr3al1rmmiiroph>lliim Eich! C. platiph:,liirm IIiers ... , . . . . .
Root Root
Root
B. 2 ' U l g Q r l S Linn. .. . iB. heteropoda Schrenk, B . zrbiliana .. . . . .. . . . ~ u x i r semper:ireiis s Linn.. . . . . . .. IB. :.aliicbiana Baill.) Ch3ndodendron caiidicaiis Sandwit h C . 1imacii:olium (Dieis) Jloldenke.
Structural t>Te of the alkaloid
Alkaloid
1 1
~
1
XXll XXll XXll XXll XXll XXVl
xx
XXI XXI
xx XXI XXI XXI XXlll XXIII
~
~
XXlll XXllI
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TABLE 3. Coniznued.
Plant part studied
Alkaloid
C. pendulus (Forsk) Diels.. . . . . . . .
Root Leaf Stem and leaf
C. sarmentosu~Diels
Root
C. frilobus DC.
All parts of the plant
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)
S a m e 01 the plant
C. leaeba DC.. . . . . . . . . . . . . . . . . . . . .
Colubrina asiatica Bronpn. . . . . . . . C . faralaolra . . . . . . . ........
Bark Leal, stem-bark, root-bark
Crcmastosperma polypklebum (Diels) Fries. . . . . . . . . . . . . . . . . . . . . . . . . . . . . Cyclca barbata (Wall.) hfiers . . . . . . . . .
Bark Rhizome
C . burmanni Hook. et Thoms . . . . . . . C . insularis (hfakino) Diels.. . . . . . . . . . . .
Root Rhizome
C . madngascariensis Baill.. . . . . . . . . . . . . . .
Root
C. peltofa Diels.. . . . . . . . . . . . . . . . . .
Root
Dapknandra aromatica F. 11. Bailey.. . . . . . D . dielsii Perkins..
.
.
.
.I
Bark
. . . . . .. . , B y k I
=
Structural type of the alkaloid
VI XXIV XXlII XXIII XXlV Undetermined Vlll Undetermined XXlll XXIV VI11 XXIIl VI
Isotrilobine 157 (59) Normenisnrine 166 169) Daplmoline 38 (69) Trilobine 163 (69) 0-Methyldauricine E a (69a) Cycleapeltine 36 (69b)
XXIll XXlV VI XXlll I VI
Limacine 64 (69b)
VI11
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 l a ) 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 (is) 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)
IV VI VI11 VI11 XXI VI11
xx
VI11 VI11 VI11 VI11 VIll VI11 VI11
xx
XXVI XXVI
xx xx
XXI XXI
xx
XXI Vlll VI11 Vlll VI VI11
xx
VI11 VI11 VI VI VI X X XXV
xxv
JAS-FEB
19791
GUHA ET AL. :
BISBESZTLISOQUISOLISE
11
ALKALOIDS
TABLE 3. Continued.
S a m e of the plant
Plant part etudied
Alkaloid
D. micrantha Benth
Bark
Daphnandrine 3 i (82) .~,O-Dimethylmicranthine 156 (13) 0-Methylmicranthine I58 (13)
D. repandula F. Muell. . . . . . . . . . . . . . !;llhnosperma rapandulum F. Muell.)
Bark
D.species . . . . . . . . . . . . . . . . . . . . . . D . species Dr-7. ..........................
Bark Bark
D.species unnamed.
Terminal twig and leaf
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)
D. tenuipes Perkins
Leaf Bark
Dryadodaphne nomguineensis (Perkins) A. C. Smith , . , , . . .
Bark
Epinetrum cordifolium Mangenot and Mibge . . . . . . . . . . . . . . . . . . Root
E . mangenotti Guill. and Debray,
Root and leaf
E . rilbsum (Excell) Troupin
Leaf, root Stem
Guattrria megalopkylia Diels
Gy~ocarpusamericanus Jacq.. . . (G. wquini Roxh.) Heracleum wllichi ......
Stem bark
.
.
Bark and leaf Root
Isolona pilosa Diels
Trunk bark
Luurelia semper7irens Tul.. . . . . Limacia cuspidata Hook. f . and Thoms.
Leaf Whole plant
Structural type of the alkaloid
VI XXIll XXIIl XXlIl VI VI VI X XXV X VI11 XXlll XXllI X XXlll XXlII
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)
XXIII XXlll XXIII
Drs-adine 104 ( 6 i ) Dryadodaphnine 105 ( S i )
XIV XIV
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)
xx xx xx xx xx xx xx
Limacine 64
xxv
X X VI X X XXV X X
xx xx
XXI
xx
XXI VI11 VI11
xx xx XXI xx VI11 I V III VI
L.obloiiga X ? r a Lindera oldhainii Hems:. . .Magnolia com~we.c.cah s i m . . . . . . J J . fuscala . h l r , , , . . . . . '.lfichr!io ; ; i c [ a t a Blume;
.
.
~
I
I
Khole plant
Leaf Bark Leaf
Limacine 6 1 ,Q3 Limacusine 44 '9.3' Lindoldhamine 11 94 0s)-acanthine 48 ' 9 5 Maqnolamine 15 '1; 1Iornoline 12 ,I;,
Vlll 1'I
I \'I
II I
JOURNAL OF NATURAL PRODUCTS
12
[VOL.
42,
NO.
1
TABLE 3. Continued. Alkaloid
M. borealis Takeda., . . . . . . . . . . . . . . . . . . Root M. fortunei (Hort.) Fedde.. . . . . . . . . . . Trunk (Berberis fwtunez Lindl.) -If.grifithii Takeda.. . . . . . . . . . . . . . . . . . . . Bark M. japonica DC.. . . . . . . . . . . . . . . . . . . . Trunk and root Trunk, root and
M.manipurensis Takeda . . . . . . . . .M. morrisonensis Takeda.. . . . . . .
Root Rwt
.\I, philippinensis Takeda
Trunk and root
Ai. sikkimensis Takeda. . . . . . . . . . .if. simonsii Takedx.. . . . . . . . .If. s;iaseyi Fedde . .
Stem bark Root See Berberis
Mmispermum caiiadense Linn.
Leaf
. . . .
Stem, root and rhizome Rhizome
.\I. dauricum DC.
Rhizome
.I.ichelia fuscala Blume. . . . . . . . . . . . . . . . Necfandra rodiei R . Schomb.. . . . . . . . . . (Ocorea rodiei)
See Jfagnolia Bark and Seed
Bark
Seed
Selumbo nucifera Gaertn
Root Embryo
.
Semuaron Tieiilardi Baill. Ocofea rodiei . . . . . . . . . . . . . . . . Pachygoxe pirhescens Benth.. . . Paracyclea insularis (Makino) Kudo and Yamamoto . . . . . . P. ochiaiana (Tamamoto) Kudo and Pamamoto. . . . . . . . . . .
Phaeanthus ebraceteolatirs (Presl) Jlerrill.. . Pleogyne cuntiinghamii X e r s . (P.auslralis Benth.)
..........
Bark and Leaf See Xectandra Root and top See Cissampelos Stem, root and rhizome
Bark Root
Structural type of the 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)
VI VI11 VI VI11 VI VI11 VI Vlll Vlll
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)
VI VI11 VIll VI VI11 VllI VI11 VI11 VI VI
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 )
I I
I
I
I I 1
IV IV VI VI IV IV Cndetermined VI11 IV XXI V V V XVI XXllI
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)
XXI
xx XXVl
xx
VI11 VI11 XXI
xx
JAN-FEB
19791 GUHA
ET AL.
:
13
ALKALOIDS
BISBENZYLISOQUINOLISE
TABLE 3. Continued. Same of the plant
Plant part studied
P>ciiarrheiia ausiraliana F. Muell.
Khole plant including root
P . manilleiuis F. Muell.
Sciadoleiila tcxijera Krulioff and -1.C. Smith . . . . . .
~
3. lapoirica 1Thunb.) Niers..
,,
, ,
,
., , ,.,.
S. rotirrzda Lour.. . . . . . . . . . . . . . . . . . . . . . . . 15.glabra rRozb.) lliers]
S.sasaiii Haj-ata . . . . . . . .
'
I
\'Ill Vlll
Vlll VI11
VI11 VllI Vlll Cndetermined
VI VI I I
Stem
Sciadenine I27 '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
xx xx xx
Root tuber
iS. discolor Spreng.)
VIll
S,St-Bienoraromoline 32 1115 ) 2-.\--Sorobamegine 69 ill@',
Siephaizia c a p i t a t i Spreng.. . . . . . . . . . . . .
5.diiabelagci Diels , , , . , . S.discolor Spreng. . . . . . . . . . . . . . . S. glabra i,Roxb.'~Miere . . . . . . . . . . . . . S.hwizaiidifoiia (Killd.) Walp., , . , . , , , , . ,
(116)
Structural type 01 the alkaloid
Bark
I '
S.cepharanlha Hayata.
Berbamine 5;
Isotetrandrine 62 I 116) 2-S-Sorberbamine 69 (116) 2-S-Sorobamegine 69 1116) Berbamine 57 11171 Isotetrandrine 62 111;) Phaeanthine 74 '11;)
Root
P . o m a t h a Diels . . . . . . . . . . . . . . . . .
Alkaloid
Root and stem See S. reriioiiii,kdia Kalp. See S. .oiiriida Lour. Fangchinoline 61 126) Root Isochondodendrine 122 '125) Isotrilobine 157 (126) (-:-Tetrandrine A; ,125) i+,-Tetrandrine 7 7 (125) Oxoepistephanine 4 i a il26a) Epistephanine 40 ( I E , 128) Root, stem and leaf Root and terresHj-poepistephanine 43 (12;) terial portion Obamegine i l (129) Insularine 170 (130) Stem and leaf Stebisimine 51 '128) C:-cleanine 121 ( 1 6 ) Tuber and above ground parte Berbamine 5; (131) Root
' Tuber
VI Vlll
VI VI
xx
VI11 Cndetermined
VI11
xx
XXIll
VI11 VI11 \'I VI VI
Vlll XXVl VI
xx
VIII VI Vlll
VI11 Vlll S?chiiosepali~mmicrophillum Eiohl.. . . . . . . Thoiictriim dcsjcarpiim Fisch. and La11 , , T.feiid1eri C . L.Anders.
Tetrandrine 7 6 1132) See Choiidodeizdron microph!llum Eichl. Root Khole plant
T.,foetidum Lim. . .
Aerial parts
~
T . glauciim Desi. , , . , T.hertiaiidezi: Tauech.. . . . T . isopjroide? C. -1.)ley.. . . . . . .
Root
I
Root Root
Berbamine 57
(1
Thalfoetidine 99 '136) Thalfine 102 '13iN Thalfinine 103 (137) See T . riigosio71 Ait. Hernandezine 81 1381 0-Methj-Ithalieopine 55 1139) Thalisopirline 53 1139) Thalisopine 54 (1%)
VI11 XI1 IX IX Vlll VllI XI1 Xlll XlIl XI VI1 VI I VI1
JOURSAL OF S - 4 T U R A L
14
PRODUCTS
[VOL.42, K O .
T ~ B L E3 . Contitwed.
Kame of the plant
T . longistglum DC.
T . lucidum,,
.
.
.
.
Plant part studied
.
.
.
.
T . minus Linn
Root
Root
Ahore ground parts Root and whole plant Root
Whole plant T . pedunculatum Edgew. . . . . . . . . . . . . . T . podocarpicm Humh. . . . . . . . . . . .
Root
T . polygamum Muh.. .I.. . . . . . . . . . . . . . . . . T . reaolutum DC. . . . . . . . . . . . . . . . . . . .
Root
T . rochebrunianum Franch & Sar.
Root
T . iugosum .lit, , . ( T . glaucum Desf.)
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. 144) 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 i a (152a) Thalirugine 14a (152a) Thalirupinine 14h (152a) Thalrugosamine 52 (153) Thalrugosaminine 55 (154) Thalrugosidine 101 (152) Thalrugosine i 5 (152) Thalsimine 86 1143)
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 VII 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 VII
XI1 VIII IX
1
JAS-FEB
19'791
GUHS E T BL.
:
15
BISBESZTLISOQUISOLISE SLKSLOIDS
TABLE 3. Contimied.
I I ~
S a m e of the plant
Plant part studied
~
T . simplex Linn.
__
Aerial part
. . . . ..
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)
Root ~
Tilincova Oiiihlaget Enpl.
Stem and leaf
Root
I
"
l
u
~'
T . mbcordaia Olir.
Root, stem and leaf Leaf Root
i
Structural t j p e of the a1ka1o1d
-
Hemandezine 81 115.5) Thalidezine 63 (15.5) Thalisamine 84 (155) Thalsimidine S5 (156) Thalsimine E6 (155, 156, 157)
Aerial part and seed Aerial part
T . sirllannbcdriir~ T . thioibergii DC.
Alkaloid
IX ~
::
1X I
1x
XVIII XVI I I VI11
VI11 VI11 rndetermined XIX I XVlll XVI I I XVlll XVlll Endetermined L-nderermined XXIII VI11 VI XXIII XXllI VI11 XXIII 1 \Ill
Aromoline 31 ( l i d )
1 Fangchinoline 61 (lil) Tetrandrine 76 rli4) Tricordatine 161 (lis) Chondrofoline 131 (li5a) Obamegine i l 1176)
i
Oxyacanthine 18
, li6)
the detection of phaeanthine in Triclisia patens; Bhatnagar ( l S l ) was partly successful in identifying and characterizing a large number of BBI alkaloids. Dragendorff'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-l aryl ether linkages remain mostly unaffected. can cleave in two n-ays.
Substituted diary1 ethers
Cleavage
at b Sowa made a systematic investigation (186, 187, 187a) on different substituted diarylethers 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.
JOCRSALOF
20
S A T U R a L PRODUCTS
5370
[VOL.42,
NO.
1
99%
-
Ph-&
-PhOH
55YG (The yield of the predominant phenol only is indicated). Scheme 3
I n 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 compound 9b from the reaction mixture formed by the reaction of 0-methylberbamine (8, R = M e ) in toluene with sodium in liquid ammonia (188).
$ a
'Q Na9 a t s Li? NH,
0'
R
e Scheme 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 pattern 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, h-@f
RE
9
b : R2=Jle,R4=Rj=Rs=OMe,R3=R6=Ri=H,R1=H~l c : R2=Me,R4=R,=Ohle,R~=OH,R~=R~=Ri=H,R1=H, d : R2=I\Ie,R4=Rs = Ohle,Rj = OH,R,= R6= R i = H,R1= H 1 e : R2=Ale,R4=Rj=Ohle,Rs=OH,R3=D,Rs=Ri=H,RI=H, f : R 2= 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 11 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 = R s=OMe,R3=Rs= Ri =H,Rl = H, R2=Rle,R4=Rs=Ohle,Rg= R * = O H , R & = R i = H,R1= H, R2=Me,Ra=Rs=RB=OiLle,R~=OH,R~=R;=H,R1=H, R 2 = b l e , R 4 =Rs = Rs = OMe,Ri= OH,R3= Rs= H,Rl = H 111 R2=Me,R3=OEt,R4= Rj = R s = O M e , R e = R i = H , R 1 = H , R 2 =hle,R3=OEt,R,=R~=OMe,R4=Re= R - = H , R l = H , R2=Me, R 3= Rs = Ra= OMe,R4= R5 = Ri = H,R1= H b w : R4=OMe,Rs=Rg=OH,R2=R3=Rg=R,=H,R1=H x : R z= Me , R 4= Rs = OMe,Ra = OH ,R3= R 6 = R, = H,RI = H,l'
JrlS-FEB
19791
GUHA ET AL.
:
BISBESZTLIS0QI;INOLISE 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; R 1 = R 1 ' = H j suggest the alternate structure 10 also for 0-methyloxyacanthine.
10
To solve the problem, Inubushi (189) deuterated the BBI molecule under condition$ 71-here only the protons ortho to methoxy groups were deuterated before cubjecting 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;=
D
R;=
R;=Me,
R~=H,R,=R;=H
1
111
I) 0-Methylation 2) Treotrnent w i t h 34/.DCl in D l 0 D
i
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= R g l= 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= R z ' = R 3 ' = h l e , R 1 = H b , R l ' = H l I) i n s c h e m e 6 (190). Isotri lobine
I
Na, N O H Lio. N H 3
1
I.ChZN1 2.Na/ Liq.NH3
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
scheme 7
I n the above scheme the -C=K-group is reduced during this reductive cleavage. Some other chromophores are also known to react with sodium-liquid ammonia, e.g., > C = 0; methylenedioxy groups can be hydrogenolyxed and converted to a single phenolic group. For example, cepharanthine yielded 90 as one of the two degradation products (192). Cepharanthine (Rz= R3 = RA = Rz' = Me, R'a-R'4
= CH2,
R1 = R1' = H I 11)
IYa/liq. S H 3 +9d+90
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(+)-tubocurarineacetate (12, R=A!Ie, X=OAc) (193). Sodium in liquid ammonia has certain limitations : (1.) A complex mixture of more than two BIs can be produced, especially from BBI alkaloids having similar substitution around ether linkages. Icupchan
JAS-FEB
19i9]
'
-
H192, 175 j-+j, 174. (2031 L ) E G R ~ D . \ T I O S :Metal-animoni.. 1234 SOTRCES : G jrorii rpit s riwi erictiii Its, P y i i i r r l i e i i u iiioiiilltiisisj Triclisiii p n t ~ i i s . l-S,l'-S
~--!-TEIRISDRISE 12321 C-,H110~Sr:A22.304"88 1IP 218: .a:?] +241,4 fCHCI.,I. 76.
k174)
46
JOURSALOF SATURAL PRODUCTS TABLE 4.
[VOL.
42, so. 1
Coniinzied.
'
UT214 (1.78), 283 (3.91). (174) 230 (1.40), 282 (3.89). (105) ORD +1490 (235), $138 (2?2), $249 (289). (215) S l I R 2.29, 2.58 ( 2 x S M e ) : 3.15, 3.31, 3.G9, 3.87 (4 x Ohre). 5.917.35 110 -i arom. H ) . (174) X ~ S622 S (?\I+,%), 621 (41), .515 ( l ) ,501 (I), 455 ( 2 1 ,448 ( l ) ,430 1 G ) , 395 119). 395 1 G 5 ) , 381 133) i@'(+T',IOO), 1ii (++, 39:. (106) DEGRIDATIOS : IIetal-ammonia. (232) SOURCES:Cocczilzis saraientosus, Cyclea barbaia, C . bzirinunni, C . peltnia, Siepiianin lierna+id$olia, S.te!randra, Triclisia sitbcordata. I
I
--
R z =R,= R?=RE=R2'= Rg'=hIe, Ri=Ri'=H.. . . . . . . .
it. ( + ) - T E T R ~ N D R(125) ISE CjE ~0~0-X-2'O Y I D E (72) C3eH420iN2. 638.299203 M P 185-190: [ a ] 2 +198 3 (CHClg).
Tetrandrine-.\'-2 '-oxide
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 ( l l ) , 200 (6), 204 ( i ) ,198.5 122)) 198 (loo), 197.5 (3), 175.5 110). 1i5 125). ( 7 2 ) SO~RCE:C y c l i a bar'baia. Rz= R = R J = R = R g = Me,R = H, R i = R i ' = H , I,. . . . . . . . . . . . . . . . . . . (Epimer of fangchinoline)
1-R ,1I-S
79. THALRUGOSISE (thaligine, isofangchinoline) (147, 152) C3;H1,06~2:608.288638 RIP 153, :.Iz5 $87 (MeOH). (147) 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 2.90 ( G x -CH,-); 3.59, 3.62 12 s -CH-): 3.76. 3.92. 3.94 13 x
(152) SOURCES:Cyclea barbatn, Thalicirztin lzictdzini, T . polgganum, T . rugoszrm, T?lzacora fimjeera.
JAS-FEB
19i9]
GUHA E T A L .
:
B I S B E S Z T L I S 0 Q ~ I S O L I S EA L K A L O I D b
Ai
T ~ B L4E . Coii+iiii,ed. I
3.88 (3 x O3Ie I : 6.28-7.39 110 s arom. H I . tl66nI
Silfi-z.G?-il x'S 1911, 623 (13j, 398 ( l l ) ,208 (9):199 (211, 192 (loo), 191 13), 176 (4). (146) S O U R ~ ET:h n l i c i r u m podocarpzciiz.
R,=R,= Ft4=Rj= R b = R?'=R31=?.le, R1= H, , € i l l = H . . . .. . . ,
, ,
, ,
,
,
~
, ,
1-6,.1'-S
81. HERSISDEZISE (thalicsimine) flSA 1
C31H,,O-S?:652.314853 MP 192-193: r a l 2 o +EO(CHci3). (138) L-1- 209 14.99), 283 (3.90). (138) ORD 71357 (229), +1490 (2352, -18.8 (2T5,1 $235 (292). (213) CD -703 (245), -166 (2731, +199 1290). (236) 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.
(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 (146) EZI~E Cj,Hd,O-S2 638 299203 l l P 136-138. [a:-i0 (1leOH) (1 46 1
UT-282 13.99). (146) CD -638 (230), +370 (2471, -217 (285). (146)
JOURR-at OF N A 4 T U R A L PRODUCTS
48
[VOL.
42,
NO.
1
TABLE 4. Continued. NhlR 2.23, 2.54 (2 x X h l e ) : 3.18, 3.62, 3.75, 3.88 (4 x OhIe): 4.85 (phenolic H ) : 5.99-7.33 (9 x arom. H ) . (146) Mass 638 (&I+, 47), 637 (18), 412 (23), 411 (go), 397 (38), 222 (11), 206 1861. 192 11001. 1146) DEGR.~D.&Iox : 'Met al-ammonia. (146) SOURCE:Thalicfr i m podoca r p u m .
R3=R4=R5= Rs= R2I= R3I= h l e , R ~ = H , R1=Hb,Rl1=H 1 , . . . . . . . . . . . , . . . . . . . . (2-A~-Demethylhernandezine)
OH
l-S,ll-S
83. TH~LIDEZISE (135) C3sHJ20;S2:638.299203 h l P 158-159 [ C Y ] +235 (CHC1,). (135) CT- 283 (4.02). (132) CD $318 1216), -466 (248), $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 fendleri, T . mznus, T . p o d o c a r p u m , T . rugosum, T . s i m p l e x .
1-S,l'-S
84. THALISAMISE (155) C39H42OiS2:638.299203 h l P 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 O l l e ) , 3.94 (1 x OMe). (155) Miss 638 (M+, 36), 219 (loo), 206 (48), 191 (25). (155) SOURCE: Thalictrum samplex.
1-s
85. THALSIMIDISE (thalcimidine) (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, recorded 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 i m p l e x . ~
1:l Mixture of two conformers of 50-methylthalsimidine
~
86. TH.ALSIVISE (thalcimine) (151) C3sH~oOiPITz:G36.283553 RIP 149-150; [a]+22.6 (CHC1,). (151) US-282 (4.23), 312 13.90). (238) ORD Positive Cotton effect, recorded only down t o 290 nm. (228) S R l R C j D j S : 2.29 (1 s S L l e ) : 3.47, 3.51, 3.89 13 s OMe), 3.82 ( 2 s 031e). (1.51)
JAS-FEB
19i9]
GUHA ET AL. :
BISBESZTLISOQUISOLISE
ALKALOIDS
49
TABLE 4. Continued. l1a-s 636 (NL,IOO), 635 O W , 621 (5l), 605 i l i ) , 499 ( l l ) ,318 ( t f24), , 235 (12), 205 tu), 190 i l l ) , 1 i 5 ( 5 1 ,174 ( 7 ) , 90 (l5), 89 ( G J . 123;. 2391 DEGADATIOS': IIetal-ammonia. ( K j SOVRCEG:Thalictriini rocliebrii~ t i a i i i i i i i ,T . rir,oosiini, T . s i m p l e x .
Type X l-R,l'-S
87. I~OTESUIPISE (85) C3sH rc,O;S, :636.283553 11P 239-241: +129 (CHClsj. (85) U I - 9 5 5 E t O H ; 210, 282. (85) XAIR 2.30, 2.58 (2 s K l I e ) : 3.16, 3.60, 3.75 ( 3 x O l f e ) ; 5.9 (1 x -OCH?O-). (85) 3 1 . k ~636 ~ (11-1, 485, 395, 198 (f-). (85) SOURCE:Dapiinatidra species.
1-5 ,11-s
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 i f f ) ,(203) SOURCES:Dabhnandrci sbecies R2 = R s= R ? '= R a '= ?rIe,R = H, R ;-R6= CH,,Ri=H .Ri'=H, .. (Enantiomer of (Tpnortenuipine)
1-R ,1I-R
R ? = R - = R > =R?'=R;'=lIe,R5-Ra = CH,,Ri=FC:,'=H. . . (= j-Tenninine
= R = Fi?' = R a =Me, Rj-R6 = C H ~ , R ! = H , . R I ' = H :' . . . . (Epimer of isotenuipine)
E,= R
89. (-)-SORTESCIPISE (8Gj [at first erroneously named .\--demethylt enuipine (82 !] CsiH3jO;S* :G22.207903 ?\IP211; [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:D a p h m i i d r n !enziipes.
90. REPASDISISE f8G) C:,H4,0rS2:G36,253553 MP 243: [CY] 0. 1817) SOURCES:Dnpiivandra d i e l s i i , D . r e p a d u l a : D . ieiiiiipes. 1-S ,11-s
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 21 S l I e I : j.15. 3 3 3 . 8.78 ( 3 1 OMe t (851 Uiss G3G (11-1.635. 485.445>444) 396. 395, 381. 364, 349. 335, 316 ( + + ) . 198 ( L - J , 192, 175 (I+) 174. , (2031
50
JOURNAL OF
KATURAL PRODUCTS
[VOL.
42,
NO.
1
TABLE 4 . Continued.
DEGR$DATION : hletal-ammonia. (86) Dnpiinandra species unnamed, D . tenuipes.
SOURCES:
Rz= R a= R 4= R z l= RBI= Me,Rj-Rs
=
CHZ,RI=H ,J,Ri'=H,. . . . . . . . . . . . . (Enantiomer of (+)-tenuipine)
l-R,l'-R
92. (-)-TEATIPINE(85) C3sH,,O;Sz:636.283jj3 1IP 110-145;[a]" -258 (CHC13). 182 I
OR%'- 703 (232),- 1040 (239), -450 (250). (215) S h I R Same as (+)-tenuipine. (85) SOURCES:
Dapiinandra dzelsiz, D .
Type X I
1-R,1 I-S
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:Berberis laurina.
Rz=&= R a =Rs=Rzl= R t l = M e , R1= R1'=H,ll,. . . . . . . . . . . . . . . . . . (7-0-Methylbelarhe)
1-R, 1 I-S
94. 0-METHYLISOTHALICBERIIVE (si) Cs~H~z06Nz:622.304288 RIP 208-209;[a]-195 (CHCla). (39) NMR 2 38,2.60 (2x S M e ) ; 3.51, 3.79,3.84,3.91 (4 x Oh'le). (39) &lass (39) DEGR4DATIOS:
Metal-ammonia.
(37,39) SOLRCE:Berberis laurina. 1-SJI-s
9.5.
0-~~ETHY-LTHALICBERIIVE
UT 278 (3.65j.1243) ORD +510 (245),-312 (280), Cd9O 1306). 1228) S L I K 2.li,2.83 (2i S h I e ) ; 3.61 (1x OMe), 3.75 (1 x OhIe), 3.87 (2x Ohle); 5.94,6.15,6.51 (3x arom. H),6.59 (2x arom. H), 6.83( 2 x arom. H),7.22 (2x arom. H).(243) Mass 622 (AIL, 52), 621 (26),607 (6). ,591 121.396 1100). 381 (18).
DEGR~DATTOIV: Metal-ammonia. (2411
SOURCES:Tiialzctrum lucidum, T. miiius, T . revolutum, T . thunbergzi.
JAN-FEB
19i9]
GUHA ET SL.
:
BISBESZTLISOQUISOLISE
ALKALOIDS
51
T ~ B L4.E Confiiizied. 12-0-Met hylt halme t hine . .
(244)
SOURCES:T h f l / Z C t 7 U ~ l~ I I ~ ? z ?T{.s : rei.olziium.
97. THALICBERISE (241: 242j Cj;H 4 1 8 0 $\;2,: 608.288638 LIP 181: $231.2. (160) UT-282 '13.81). (141j CD $2490 (214), -122 (250), ;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 O I I e ) : 6.07-7.20 (10 x arom. H ) . 1141) X ~ S608 S N-), 607, 501, 485,,417, 418, 396, 395, 381, 304 (++)L 198 ( + - j , 192, 175 (+-I> 144. (240) DEGR-ID-ITIOS:Metal-ammonia.
l-S,l'-S
1-s
' 1
I
1241)
SOURCES:T1ialictriii)i Iircidzini: T . ? ~ ~ i i t uTs., i h u n b e r g f i . 98. THILVETHISE (244) Cg6HgsO~S*:592.25;338 RIP 275-277: [a]*'7 2 0 0 . (244) Miss 592 iW-), 591 (93!, 577 16), 545, 469, 295 (-ti-),273 (T+). 12401
Type XI1
CjcH,,O-S,.638.299203
1IP 168-170: [a;'' -88.6 (CHC13). (13gi US- 2 i 0 (3.87), 285 13.87). (246) O E D -120 1230), $33 (24B!, f2.5 (2GO), +30 1278), -33 (295). 12281
2.70 ( 2 s S ? \ l ~3.32, j: ' SiTF2.32, 3.51, 3.77, 3.89 (4 s OlIeI; 6.33 1
~
.
( 2 x arom. H ) , 6.40 (1 s arom. H ! , 6.47 ( 2 x arom. H I . 6.75 12 x aroni. H ) . 1246) bI.iss 638 (LI-, loo), 637 (4W, G23 (9),7-!6 ( G ) , 515 ( 2 ) , 417 (63), 402 (01) 71.3 (67). 206 (IS), 190 ( E I ) , 176 yi), 174 ( 5 ) , 90 (4), 89 ( 2 ) . (239) DEGRLD.ITIOS: Metal-ammonia. 1245 I
SOURCE: Thalictruni foeizdzivz.
JOURSALOF SATURAL PRODUCTS
52
[v-OL. 42,
NO.
1
TABLE 4. Continued. Rz= RB= R = R = R 2 ' = Ra = Rql =Me> RI =H, , R I ' = H I,, . . . . . . . . . . . . . . . ,
l-S,lI-S
(12-O-Meth~-lthalfoetidine)
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). (228) 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, 213 (loo), 204, 190. (194, 240) DEGR~DATION Metal-ammonia. (194) >SOL-RCESThalictrirm das>carpum, T . luczduin, T . re~olutzini,T . rzcgoszm
Rz= R3= Rz'=R3I= R4'=RIe,R4=Rj=H, RI=H,,R1'=H,,I.,
. .. . . ,
. .. . . . . . . . . . .
l-S,l'-S
lOOa
THALIGOGIDIYE i152a) . .
(152a) UT- 275 (3.72), 283 (3.72). (152a) C D -318 (224), +54.9 (242), $67 (268). -190 (287). (152a) S L I R 2.25, 2.66 (2 x " e ) ; 3.49, 3.75, 3.86 (3 x O l f e ) : 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. (152a) SOURCE:Thalictruni rugosiiin.
1-s,11-S
101 TH~LRGGOSIDIYE (152) C3nHI+), 490, 403, 297, 191. (57)
SOURCE:Cissanipelos oialifolia. 147. DI\IETHTLDIHYDROITARIFTEIP;E (,57) 6Tosicoferine is retained in the table since Cava et al. (54) though, that in “vie%-of its ease of isolation and its apparent behaviour as a single compound, it will undoubtedly be encountered in future phytochemical investigations”.
JAN-FEB
19i9]
GUHA ET AL.
: BISBESZYLISOQUISOLISE
ALKALOIDS
63
TABLE 4. Continued. C,,Hd,O&P :622.304?88 1I.iss 622 (JI-),518, 503, 417, 311, 204. ( 5 7 ) SOURCE:Cissniiipelos oraltfolaa.
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. (57) SOT-RCE:Cissniiipelos oimalgoiia. 150. ~IETHYL~T-.~RIFTE:SE (57)
11-11
C1;HzjOES2:606.2729ES
X i s s 606 (II-), 502, 486, 459, 430, 312, 311. ( 5 7 ) SOURCE: Cissanipelos ozlalqolia.
R , = H, R 2 = Me o r v i c e versa
151. \T.\RIFTEISE( 5 7 ) Ci,11360ES2:592.257338 11.1s~592 (llT), 488, 473, 445, 417, 416, 297. ( 5 7 ) SOCRCE: Cis:enipelor oralifolia.
1'-R
' R , = H, R,= R,=
R40
'
Me or v i c e v e r s a
H, R + = M e o r v i c e v e r s a
Type XXIII R 2 ' = R 3 ' = M e , R 2 =R s = H , R1=H,,RI'=H'". . . . .
. . . . . . . .1
l-.S,l'-S
132. COCSOLISE 12662) C IrH-20,S2:548,231123 MP amorphous powder: [a]+204 (CHC13). (SO) 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); 3.614.0 (10 Y arom. H ) : 4.33 (tm-o deuterium exchangeable protons) (262) MISS 548 (AI-), 336, 335, 321, 168. (661 SOKRCE:Cocculus peuditlits.
1-S,l'-S
153. COCST-LISE (eferine, trigilletine) (66) C3jH3~0,S2:5C2.24GT73 3IP 272-271: [a: 1 2 8 0 ICHC13). (66) Uf- 234 (4.72), 275 sh (3.731, 289 (3.771, 307 sh (3.59). (175)
~
~
1
64
JOURKAL OF NATURAL PRODUCTS TABLE 4.
[VOL.
42,
NO.
1
Contkued. S h l R 2.35, 2.56 ( 2 2: Khle); 2.613.60 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) 11 562 (lI','39); 350 (32), 349 (loo), 348, 335 ( 3 5 ) , 175 (70). (66) DEGR.\DITION : IIetd-ammonia. (66) SOURCES:Coccdits pendidus, Triclisia gilletil, T . p a t o i s .
1'-R
154. 1 , 2 - D E H r D R O ~ ~ I C R , ~ S T H I S E (83) Cs4HsaOjN2:54G.215473 h'lP 188-194; [ a ] 2 -150 0 (CHC13). 183 )
Vf7-i35 (3.4). (83) S M R 2.55 (1 x SAIe): 3.85 (1 x OhIe). (83)
RZ= R3'= l I e , R 3= R Z 1 =H, Rl=H,,R:'=Hl , I . . . . . . . . . . . . . . . , . . . .
SOURCE:Dnbiiiiandra sbecies unnamed. 1-SJI-s (24) C34H9zOjSz:.j48.231123 l f P 256-258; [ a ] 2+332 0 (pyridine). 124) 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 ( T 2 ) , 167 (16). (24) SOUKCE : 4 nisocyclea gradidieri.
R 2 =R3= R2'= R3'=Me, Ri=HlI ,R,'=H,. (Enantiomer of isoirilobine)
R2= R, = R2'= Rdl=hIe, R1= H, , P \ i ' = HI (2-~Y-lIeth~-l-12-0-metli~-lcocsoline)
l-R,l'R
Uf%36 (33.5). (263) KhIR 2.49, 2.59 ( 2 x K l l e ) ; 3.84, 3.96 12 x O l I e ) : 6.13, 6.30 12 x highfield arom: H ) . '(13) hIass 376 (11-).(13) DEGHADATIOK: Photolysis. (13) SOURCES:Depknaiidra micrcn!ha, P.species D?-7, D . species unnamed. 1-s ,11-s
157. ISOTRILOBISE (homotrilobine) (190) 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 O X e ) ; 6.13, 0.30 (2 x high field arom. H ) . 113) M i s s 576 fll-),3.50. 349. 3%. l i 5 (++, 100). (203) D E G X ~JTIOA D : Metal-ammonia (190)
US-FEB
19T9]
GUHA ET AL.
:
BISBESZTLSIOQUISOLISE
TABLE4.
ALKALOIDS
65
Contirzzted.
SOURCES: Dapiivaridra ~riicrontha, D . sbccies Dt-7, D.sbecics unnamed.
R ? = RE = H,Rz'= R B ' = l I e , R,=R,',Ri'=H,. . . . . . . . . . . . . . . . . . . (Enantiomer of cosdoline)
R B= Et,'= R 3 ' = ~ I c R, : , = H, Ri=P,i'=H . . . . . . . . . . . . . . . . . . . (Epimer of 0-methylniicranthine)
1-R;l'-S
Illdl
UT. 227 (-&.GO), 275 ~ 1 1(3.69i, 284 (,3.71),304 ( 3 . 4 4 ) . (17.5) S l i R 1nsolubilit~-in c3mriion cirgouic solvents precluded t h e recorciing of nnir spectra. i l i 5 ) ;\I.\ss 548 2 ~ ! ,330 (31 I ; 235 (1001, 321 (321, 108 (-19). 1175) SOURCE:Tiiclisiri sii'iccrd,i!a.
sh (4.21), 311 .;h (,3.4G), 351 (3.05). (172) S 1 I R 2.40 11 x S 1 I e j : 3.92, 3.99 ( 2 s OlIe I ; 5.86-7.29 (10 s aroni. H i . 7.39. 8.34 12 x aroni. H J .
R,= R a = It a' = N e , R y l= H, R 1= H b
' =H
. . . . . . .
66
JOURSALOF
S.4TURAL PRODUCTS
[VOL.
42, so. 1
TABLE 4. Conlinued.
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:Anisocyclea grandidieri, Cocciilus iiirsutus, C. l a l t r i j O l i l k S , C . sar?izentosits, C. trilobus. Type XXIV
Rz=R3=R2'=RIe,R4=R3'=H, R1 = H, , R ' = H I ~ ~. I ,. . . . . . . .
1-s,1 I-s
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~Iztspendulzis.
MeNw 1%. ~ I E N I S ~ R (268) ISE
C~~H3~0eN~:590.241688 RIP 203; [a]$149 (CHCla). (217) SOURCES:Coccitlzts leneba, C .
'
Me
\
0-Demet hy1,menisarine (exact location of OH is not determined
166. NORMENISARI~E (269)
c gH&~~,:576.226038
RIP 223; [a]*'+I90 (CHC13). (269) SOURCE:C o c c ~ d i t strilobits.
R2= R S= Rd= R2'=JIe,R5 =H,Rl = R'=H, stereochemistry undetermined
R 2 = R = R I= Me, €1rR = CH,, R , = El'= H, stereochemistry undetermined. . . , . . .
. .
167. PSEUDOREPINDT-LIKE 183) C,iH3,0~N,~606.27298S RIP 168-173; [a]'*+2ZY (CHCI,). 183 ) NRIR (83) MAWGOG i l l T ) , 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) 5 1 . m 020 (AI-), 379, 204, 1 i G . (271) DEGRADITIOS: Met al-ammonia. 1270)
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GGHA ET AL. :
67
BISBESZYLISOQUISOLINE ALKALOIDS
TABLE 4.
Contztiued.
SOL-RCEB:Daphnandra dielsi:, D . repaiidiila, D . tenuipes.
Type XXVI 1-R ,I '-E : ?\letel-ammonia. (273) SOVRCE : C y 1ea inszt la ris .
DEGR.ID.&OS
Rt = Rt = R, = €3 P I = R3I =Me, R,=Ei'=H 11,. (7-0-me thylinsulanoline)
170. IKSULARIXE 1274, 2 7 5 , CsjH,cO& p:G20.288638 31P 157. [a]" f11.36 (EtOH). (59) UT' 200'(4.68), 229 s h (4.56), 276 (3.64). (59) K l I R 2.45, 254 ( 2 s N M e ) : 3.30, 3.75, 3.82 (3 s O l I e ) . (216)
l-R,l'II
ART1F;ICT
'
1-s,1'-s
( G ) , 313 (201, 312 (loo),311 i%), 310 (74), 309 ( 2 6 ) , 204 (141, 190 (l?),1i4 (191, 159 (8),146 ( 8 ) > 140 (9). ( 2 5 3 ) DEGRADATIOS: Metal-ammonia. 1274) SOKF:CES:Cissanipelos insftlaris, C. piireira, C y c l m ziisitlaris, Po m c y c l e n ochiaio)ia, Stephu7iio japoiiicci.
171. S O . 16 179)
+
CcsH:,O~S,C1*:636.31993ST. t . o € chlorine.
1
1
1IP 213-21i; [al'j 1156 iCHC1:). 1791 UT' 283 (3.88). 179) KAlR 2.37, 3.30 12 KMe): 3 7 5 ( 2 x O l I e ) , 3.94 12 s OhIe). 4.6 (1 x -CH2C1), 5.8-T.7 (10 1 aroni. H ) (59) SOURCE.Cyclea p e l t a f a .
BBI .1LKhLOIDS OF U S I ) E T E R l I I h-ED STRUCTURES 172. DIXKLXEISE C36Hjs0,S2:.j9i.2i2988 1IP 285; [a; -24.4 (CHCl,). (124) SOTRCE: Stephanie diukelagei.
SOL-ECE:Bcr3e;is liiriinlaica.
175. (I! - ~ E O C H O S D O C C R . ~ R I S E Ca,H,,06Sp-- 25-lF24.319938 I I P 268 (chloride): [a!2o+I79 iH?O! (chloride). i2iG;l SOURCE: Curare. 176. OCODENERISE Ca;H,rO:T,:BOS."88fi38 3IP 275 (chloride): [a: -170 (HzO) ich!oride 1. (107) rodiei. ~ O U R C E-\-ecfnndrn : 177. Oroc.lwsE C jrHacOJ~:G08.2S8638
SOL-RCE:Ccrnre.
(chlnride'. (107) SOURCE: X e c t c i i d r n rodiei.
JOURKAL OF NATURAL PRODCCTS
68
[VOL.
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NO.
1
TABLE 4. Continlied. 178. PENDISE C3jII3~ossz:578.241588 blP 170-171; [a]+278 (CHCI3). (G6) SOURCE:Coccidiis penduiiis.
183. T I L I A C O R I D I S E C39Hao0,Nz:GG4.278468 hIP 153-1515. (167) SOURCE:Tililicora racemosa.
179. PESDULIKIXE C3jH,406~2:578.241688 RIP 272-273; [a]$285 (CHC13). (66) SOURCE:Coccltlirs p z d d u s .
184. TILIANDRISE C,aH340jN2:5j0.246773 LIP 175; [a]f408 (EtOH). (74) SOURCE:Ti!iacora trinndra.
180. PROTOCHOSDOCURARIKE C3iH,,06S,+X-:609.301210 YIP 265 (nitrate); [a]20 +l78 (H20). (2761 SOURCE:Curare. 181. PYCS.\RRIIENAbfINE C3a€Id&z :632.273383 MI' 203. (117) SOURCE:P?Ncnarrliena matiillpnsis.
135. TILI.iRTKE5 C?sH34OjS2:562.246773 hlP 203-207; [CY]+283.G (hIeOH). (170) SOURCE:Tzliacora racemosa. 186. TOMCSTOCURISE Cas1~,,06Nz:594.272988 MP 260; [a]'8 +202 (0.1K HC1). (5@) SOURCE:Chondrodendron toi?zentoszinz.
182. PYCSARRHENISE C Z B H ~ Z O:646.289033 YNZ 1IP 193. (117) SOURCE:Pycnurriierla m a n i l l e m i s . 6Both ti1iacorir.e ( S o . 118) and tiliarine, isolated from the same source, were considered by Rao and Row (277) t o have structures of the same type. But now the structure of tiliacorine has been modified; no work has been done on tiliarine.
TABLE 5. Names a d s y ~ o l t y ~ i ozfs 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
JAS-FEB
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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 'rhBLE
Fangchinoline 61 (*):Fangchinoline 58 Funiferine 20 Funiferine -Y-oside 21
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 1 3 Sortiliacorine-;i 115 Kortiliacorinine-Al 116 Sortiliacorinine-B 117
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 (+)-Iqochondodendrine Isofangchiiioline i 9 Isoliensiniiie 28 Isotenuipine S i Isoletrandrine 62 Isothalidezine 82 Isotiliarine 115 Isotrilobine 1.57 Krukovine
5 . CO?ZtZ??Ued.
li4 122
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 ' - A Y - M e ~lberbamine h~ 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 ?rIethyl11.I-.L.~KBH\IIK.~STH.~M and 11.J . MITCHELL. 1975. Panurensine and norpanurensine, new bisbenz\-lisoquinoline alkaloids from d bic!u pamtrensis. J . O r e . 23. Si.\,J . II.,AI. I-. L.iKSH\lIK.iSTH.iM, 11. J . R~ITCHELLand )I. P. C.k\-.i. 1976. Iirukovine, a nen- bisbenzylisoquinoline alkaloid from Abitia spleiidide Krukoff and Moldenke. J . Org. Ciieiii. 41: 317-319. 24. SCHLITTLER, E. and S.WEBER. 1972. dlkaloids of Aiiisocycleu graiididieri H. Bn. QIenispermaceae). H e l ? . Ciiein. A c i a 55: 2061-2064. 25. KISG, H. 19-15. Curare alkaloids. Part 1-111. Examination of commercial curare, Ciioizdrodedroii ionie~iiosiiiizI? and P and d ~ i o i ~ i o s p e r i i zgmiid~;fo!iiciiz i~~~z Eichl. J . Ciieni. S 0 ~ . 1 9 4 81945-19-19. : 26. GOI-ISDACH.~RI, T. I?. and S . I-Is\I-.\s.~TH.~s. 1967. The identity of aristolochine. Indian J . Ct'ieni. 5 : 655-6613. 2 7 . BICK,I. R . C. and G. K .DOUGLAS. 1965. Itherospermoline, a ne-- bisbenzylisoquinoline alkaloid. Ciieni. 2 I d . 1965: 891-095. ~
74
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28. BICK, I . R. C., P . S. CLEZYand W. D. CROJV. 1956. The alkaloids of A f h e r o s p e r m a moschatum. I. Isolation of the alkaloids and structure of berbamine. A u s t r a l i a n J . Client. 9: 111-119. 29. TOMITA, M. and T. KUGO. 1955. illkaloids of berberidaceous plants. 1-11. Alkaloids of Berberis amurensis m r . japonica f o r m a bretschneideri. 1. J . P h u r m . SOC.Japan 75: 753-755; C h e m . A b s f r . 49: 13597a (1955). 30. POMMEREHSE, H. 1895. Beitrage zur Kenntnis der alkaloide von Berberis aquifolium. Arch. Pharm. 233: 127-171. A . K. BAREAand A. K. DASGUPTA.1954. Plant alka31. CHATTERJEE,R., A. BAKERJEE: loids. Part J-I. Berberis asiatica Roxburgh. J . Indian C h e m . SOC.31: 83-84. 32. CHATTERJEE,R. 1951. Plant alkaloids. Part I. Berberis j'loribzcnda Wall. Ex. Don. J . Indian C h e m . Soc. 28: 226228. 33. CHATTERJEE, R., ?*I. P. GCHAand A. K. DASGUPT.I. 1952. Plant alkaloids. IV. B e r beris himalaica Ahrendt and B . tinctoria Leschenault. J . Indian Chem. Soc. 29: 921-924. K . L. LUFTFULLIK and S. Yu. YUSUSOV. 1976. 34. KARIhlOV, A., b1. I-.TELEZHESETSKAYA, Alkaloids of three Berberis species. K h i m . P r i r . Soedin. 19i6: 558-559. D., B. BRAZDOYICOVA and J. TOMKI. 1976. Alkaloids from Berberis julianae 34a KOSTALOVA, Schneid. 11. Chem. Z r e s t i 30(2): 226-228. 35. YASG, T. H. and S. Lu. 1960. Alkaloids of berberidaceous plants. XXV. Alkaloids of Berberis kawakamii. 1. Yakugaku Z a s s h i 80: 847-849; C h e m . A b s t r . 54: 231871 (1960),., 36. CHATTERJEE, R. and A. BAKJERJEE.1953. Plant alkaloids. Part V. Berberis lambertzz Parker. J . I n d i a n C h e m . SOC.30: 705-707. 37. FALCO, R l . R., J. X . DEVRIES,Z. M a c c ~ oand I. R. C. BICK. 1971. Belarine, a new bisbenzylisoquinoline alkaloid. J . C h e m . Soc. D 1971: 1 0 ~ - 1 0 5 7 . 38. FALCO, ?IT. R., J. X . DEVRIES,Z. M.~CCIO and I. R. C. BICK. 1969. Alkaloids of Berberis laurina Billb. 11. Two new phenolic biscoclaurine alkaloids. Experientia 25: 1236-1237. 39. FALCO. M. R., J. X . DEVRIES,A. G. DEBROVETTO, Z. ?*lacc~o,S. REBUFFOand I. R. C. BICK. 1968. TR-o new alkaloids from Berberis laurina Billb. (1). Tetrahedron L e t t . 1968: 1953-1959. 39a. h'11.1S.4, G. A., M.IKRAN and S. A. WARSI. 1969. Spectral studies on alkaloids. 111. Identification of berbenine as berbamine. P a k . J . Sci. Znd. Res. 12(1-2): 159-160; C h e m . A bslr. 72: 55716e (1970). 40. YANG, T. H. and S. Lu. 1960. Alkaloids of berberidaceous plants. XXVI. Alkaloids of Berberis mingetsensis. I. Yakugaku Z a s s h i 8 0 : 849-851; Chem. A b s t r . 54: 23188a (1960). 41. YANG,T. H. 1960. Alkaloids of Berberidaceae. XXVIII. Alkaloids of Berberis morrisonensis. Yakugaku Zasshi. 80: 1302-1304; Chem. A b s t r . 55: 30005g (1961). 42. KARIMOV,A., A I . S7. TELEZHENETSKAYA, K. L. LUTFULLIN and S. Y. YUSUSOV. 1977. Berberis alkaloids. S e w alkaloid oblongamine. K h i m . Prirod. Soedin. 1977: %83. 42a. KSRIMOV,A., AI. I-. TELEZHESETSKAYA, K. L. LUTFULLIN and S. Y. Y u ~ n s o v . 1978. Alkaloids of Berberis. 2'-S-methylherbamine from Berberis oblonga. K h i m . P r i r . Soedin. 1978(2): 227-231; Current Abstrac!s o j Chewiisiry and I n d e x Chemicus 7 0 ( 5 ) :273113 (1978). 42b. hTI.iiv.i, G. A . and M . IKRAM. 1970. Alkaloids of Berberis betiolaris. P a k . J . Sci. Znd. Res. 13(1-2): 49-51: C h e m . A b s t r . 73: 117192n (1970). 43. GREITHOU~E, G. A. and N. E. RIGLER. 1940, Isolation of the alkaloids, berberine and berbamine, from Mahonza swaseyi. P l a n t . Physzol. 15: 563-564. 44. TOYITA,31. and T. H. YASG. 1960. Blkaloids of berberidaceous plants. XXIV. Alkaloids of Berberas fhunberazi. 3. Yakupaku Zasshi 80: 845-846; C h e m . A b s t r . 54: 23187h (1960). 45. TOMITA, M.and T . KUGO. 1959. Alkaloids of berberidaceous plants. Y I X . Alkaloids of Berberas trchonoskyana. I. Isolation of bases. Yakugaku Zasshi 79: 317-321; C h e m . A b s t r . 53: 17161e (1959). 46. OREKHOV, A. P. 9133. Alkaloids of Berberis heteropoda. A r c h . P h a r m . 271: 323-327. 47. SPITH, E. and A. KOLBE. 1925. Zur Kenntnis des oxyacanthins. B e r . 58: 2280-2285. M. and F. KHAS. 1977. Chemical investigation of Berberzs zebzlzana. P l a n t a 47a. IKRIY, M e d . 32(3): 212-213. R4. 1896. Uber bebirin. B e r . 29: 2054-2058. 48. SCHOLTZ, 40. BARLTROP, J. A. and J. A. D. JEFFREYS. 1954. Curare and related topics. Part I. 9 preliminary examination of Chondodendron limaczifolzum. J . Chem. Soc. 1954: 159-164. 50. BICH,I. R . C. and P. S. CLEZY. 1960. Tertiary bases from Chondodendron tomentosum. J . C h e m . SOC.1960: 2402-2407. 51. DUTCHER,J . D. 1952. Curare alkaloids. 11. The purification of d-tubocurarine chloride and the isolation of d-chondocurarine. J . A m . Cheni. SOC.74: 2221-2225. 52. DUTCHER,J. D. 1946. Curare alkaloids from Chondodendron tomentosum Ruiz and Pavon. J . Ant. Chem. SOC.68: 419-424. 53. KISG, H. 1947. Curare alkaloids. Part 1-1. -1lkaloids from Ckondodenron f o m e n i o s u m . R . and P. J . Chem. SOL.1947: 936-937. 54. CAVA,M.P., J. KUXITOXO and 4 . I. DAROCHA.1969. The alkaloids of Chondodendron toricoferunz. P h y f o c h e m i s t r y 8: 2341-2343. I
JAS-FEB
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:
BISBESZTLISOQCISOLISE
r -
la
ALKALOIDS
55. KOSDO,H., AI. TOMITA and S.UYEO. 1937. S i n o m e n i u m and Cocculus alkaloids. XLT-I. llethylisochondodendrine.B e r . 70B: 1890-1893. 56. FERREIRA, 11.A , , L. S . PRISTA, C. ALVESand -1.S.ROQL-E.1965. X chemical study of Cissampelos mucronate. I . Isolation of d-isochondodendrine. Gurcia O r f a . 13: 395406; Chent. A b s f r . 67: 100295b (1967). 57. SSEDDES,F., R. B. PARKERand C. GORISSKI-. 1970. Electron impact studies in medicine and biochemistry-11: The mass spectra of the alkaloids from Cissampelos o;malitolia DC. Org. -1Iass S p e c f r o m e t r y 2.: 607-614. 58. KrPcH.is, 6 . 11.,1.C. PATEL and E . FL-JIT.~. 19G5. Tumor inhibitors. 1.1. Cissampareine, new cytotoxic alkaloid from Cissenipelos pareira. Cytotoxicity of bisbenzylisoquinoline alkaloids. J . P h a r m . Sci. 54: 580-583. 59. DWLXA-BADL-, D., J . S. K. A i m , C. A. ~ I I S G L EA,. S . TACKIE,D. .J. SLATKIS,J . E. KS.IPP and P. L. SCHIFF,J R . 1975. Constituents of West Africsn medicinal plants. 10. Alkaloids of Cissumpelos pareira. Ph;t,tocheniistry 14: 2520-2521. GO. HATSES,L. J., E. J . HERBERT and ,J. R. PLImmR. 1966. (++)-4--0-Methylcurine from Cissempelos pareira L . J . C h e m . Soc. C 1966: 615-617. 61. ROYCHOL-DHL-RT, A . 1972. Chemical investigations on Cissampelos pareira Linn. Sci. Culture 38: 358-359; C h e m . d b s f r . 78: 82058s (1973). 62. TRIP.ITHI,T:. J., &&.B. ROYand B. D.ISGUPTA.1976. -1lkaloids of Cocculics hirsutus DC. Indian J . Chem. Sect. B 14B: 62-63. 63. To11ir.1, 11. and F . KUSGDA.1953. Alkaloids of menispermaceous plants. CI. Alkaloids of Cocculus iaitrqolius. P h a r m . B u l l . (Tokyo) 1: 1-5; Chem. il b s t r , 48: 12131f (1954). 64. BEAL-QGESSE, L. 1938. Some medicinal Menispermaceae of the species T i n o s p o r e and Cocczlus. B u l l . Sci. Phurmacol. 45: 7-14; Chem. A b s t r . 32: 308g4 (1938). 65. SISH.~]A . 1960. Chemical examination of the leaves of Cocculus lueba. I . Basic and nonbasic constituents. J . P r o c . Inst. C h e m . (India) 32: 250-252; Chem. A b s t r . 5.5: 18886b (1961). 66. BHAKL-SI, D. S.and P. P. JOSHI. 1975. Alkaloids of Cocculus pendulics (Forsk.) Diels. Tetrahedron 31: 2575-2579. 67. TOUITA,11.and H. FL-RUKAX-A. 1963. Alkaloids of menispermaceous plants. CXCI?. Alkaloids of Cocculits sarmentosus. 4. Structure of water soluble quaternary aporphine alkaloids] cocsarmine. l'akugaku Z a s s h i 83: 190-194; Chem. A b s t r . 59: 3971h (1963). 1969. Studies on the alkaloids of K., H. FCRCKAU-.~, K. SATOand J. TAKAHASHI. 68. ITO? menispermaceous plants. CCL. Structure of Coclobine, a new biscoclaurine alkaloid from Cocczilzis trilobus. Yakugaku Z a s s h i 89: 1163-1166. 69. ISL-BL-SHI, T. 1955. Studies on the alkaloids of menispermaceous plants. C S X I ? I . Structure of trilobamine (daphnoline). P h a r m . Bull. (Tokyo) 3: 384-387. 69a. TSCHESCHE, R . , R . GOEPELand H.-W. FEHLHABER. 1970. Uber die isolierung von o-methyldauricin aus Colubrina asiatica. Phytochemistry 9: 1683-1685. 69b. GCIS.~~-DE.IU, H., ?.I. LEBOEUF, &I.DEBR.AT: A . CATEand R. R . PARIS. 1975. Alkaloids oE Cclzibrina farnluotra subspecies faralaotra. Plantu X e d . 27(4): 304-318. I. NOGUCHI, D. L. EDIEand A . I. DAROCHA. 1974. Phlebi70. CAVA,11. P., K. WAKIS.~KA, cine. a new biohenvlbisbenzrlisooninoline alkaloid from CremastosDerma polsbhleburn. J . Org. Cheni. 59: 3i88-3591. 71. TOVITA,AI., AI. KOZCKA and 11. SATOXI. 1967. Alkaloids of menispermaceous plants. CCXXSS-. -1lkaloids of Cyclea borbata. I h k q u k u Zasshi87: 1012-1013; C h e m . d bstr. 68: 3052h (1968). Tla. YL-PRIPHAT: T., P . P.icH.iI.i- and F. Z~-M.ILKO~.SKI.1974. Alkaloids from the Thai drug Krug Kha l l a o (Xeiiispermaceae) 111. Isolation and identification of further his(benzylisoquinoline) alkaloids of the berbamine and osyacanthine t:-pe. Planfa M e d . 25(4): 315-324. 72. DAHEM, K., P . PACHALY and F. ZTMALKO\WKT.1977. Alkaloids from the Thai drug Krug Kha M a 0 ( C j c i e a burbate, Menispermaceae). I-. Isolation and structural elucidation of further bisbenzylisoquinoline alkaloids. A r c h . P h a r m . (Weinheim, Ger.) 310(2): 95-102. i 3 . GOEPEL, C., T . YUPR.APH.~T, P . PACHALIand F. Z~X~LKOILSKI.1974. Alkaloids from the menispermateae drug Krugh Kha Mao (Cyclea b e r b a f a ) from Thailand IT-. Isolation and structure of two berbamine alkaloids. P l a n f a X e d . 26: 94-97. 74. PARIS,R . R. and S.K. SASORITH.1967. Alkaloids of Cyclea barbata and Tiliacora triandra, tn-o menispermaceae from Laos. Ann. P h a r m . F r . 25: 627-633. 7 5 , HOFFSTADT, B., D. MOECKE, P. PICHALT and F. ZYI\I.ILK~~-SKI. 1974. Alkaloids from the Thai menispermaceae drug Krug Kha RIao. 2. Isolation and structure of a neF berbamine alkaloid. Tefrahedrou 30: 307-310. G. R . and 11.L. DHAR. 1958. Chemical examination of the roots of Cyclee 76. CHOCDHURY. bzirnianni. 1.Sci. Ind. Res. (India) 17B: 163-166: Chem. A b s t r . 52: 20454i (1958). ( I . KIIXCHI, T . and K. BESSHO. 1958. Alkaloids of menispermaceous plants. CLSXI. Alkaloids of Cyclee insztleris. 15. Isolation of t R - 0 new tertiary alkaloids, insulanoline and norcvcleanine. Yakugnku Z a s s h i 78: 1408-1412; C h e m . A b s t r . 53: 7219f (1959). "
7-
I
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NO.
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TOUIT.I,11. and T. KIKUCHI. 1957. Alkaloids of menispermaceous plants. CXLV. alkaloids of Cyclea instileris. 9. Isolation of bases. J . Pharni. Soc. J a p a n 77: 6943; Chent. A b s f r . 51: 96461 (1957). 79. KUPCHAN, S. ll.,-4.J. LIEP-I, R . L. BAXTER and H . P. J. HISTZ. 1973. New alkaloids and related artifacts from Cyclea peltate. J . Org. Client. 38: 1846-1852. S. M.,S . YoIcoYanra and B. S.THYAGARAJ1961. Renispermaceae alka80. KUPCHAS, loids. 11. The alkaloids of Cyclea peltata. J . Pharnt. Sci. 50: 164-167; Ciieiit. A b s t r . 55: 10806e (1961). 1948. Alkaloids of Queensland flora. 111. Alka81. BICK,I . R . C. and T. G. KHALLEP. loids of D a p h n a d r a aroinatice. GnP',. Qiieenslaitd P a p e r s . D e p f . Clieni. l(33): 7 ; Cheni. A b s i ? . 43: 6787g (1949). and A. R.TODD. 1953. Alkaloids of Daphneiidra species. 82. BICK,I. R.C., W.I . TAYLOR Part J-. An examination of the alkaloidal content of D . m'crantlie and D . tenuipes. Isolation of some minor Daphnandra alkaloids. J . ciieiii. Soc. 1953: 695-700. 1975. Alkaloids from a new 83. BICI~,I. R. C., H . 11. LEOWand S. SOTHEES\Y.IR.~.S. Depiznendra species. Isolation and structure of pseudorepanduline. Tetrahedron L e f f . 1975: 2219-2220. Y . 1946. A\lkaloids of Queensland flora. I. Alkaloids 84. BICK,I . R . C. and T. G. WH of Dapiim?idra repnndirla. 1 QyeeiLsliznd P a p e r s , D e n t . Clieni. l ( 2 8 ) :8 ; Cheni. A b s t r . 41: 1390a (1947). 85. BICI~,I . R. C. and IT. I. TAYLOR.1 9 i l . Alkaloids of Dapliiinndra species. Part X . The structure of isotenuipine. J . Ciieni. Soc. C 1971: 3779-3783. and3I. J. 1-ERSESGO. 1963. The structure of tenuipine, 86. B I C I ~I., R. C., J. HARLEY-X~SOS nortenuipine and repandinine. d n n l e s Asoc. O i r i i i i . A r g . 5 : 135-147. and R. I . T-LYLOR.1969. Alkaloids of Dryadodaphne 8 i . BICIC,I . R . C., G. K. DOUGLAS nocogziineensis. J . Chein. Soc. C 1969: 1627-1632. 88. DEBRAT,ll.,hl. PLATand J . L. h1.1~. 1966. Alkaloids from African RIenispermaceae: Epineiriiiiz cordifoliiiiii and Epinetriini nraiigenotii, isolation of cycleanine, norcycleanine and isochondrodendrine. 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. Epinetrzwi ;#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'-0-1lethylcurine and (R,R)(-,-)-O,O-dimethylcurine, t F o new natural alkaloids from Guatteria megalophyiln Diels. Gazz. Chinz. Ital. 105: 1207-1213. 90. R ~ T TL. - , R . and A. S. R. ANJANEYULU. 1962. The alkaloids of Gyrocarpiis jacqirini Roxb. J . Sci. Ind. Res. (India) 21B: 581-582. 90a. GUPTA,B. D., S. K. BANERJEE and K. L. HASDL 1976. Alkaloids and Coumarins of Heracleuwz sallichi. 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, h n o n a c e a e . C. R. Aced. Sci. S e r . C. 285 114): 447-43. 91. BIISCHI, E., J. A. G.IRB\RINOand F. GIORA. 1962. Lazirelie semperoirens alkaloids. Gazz. Chim. Ital. 92: 818-822; Chem. A b s t r . 58: 4614c (1963). M., H. FURVICATYA and K. FUK.IG.ITT-.L 1967. Alkaloids of menispermaceous 92, TOMITA, plants. CCXXXI. Alkaloids of Liiiiacia cuspidata. 1. The structure of limacine, liniaciisine and cuspidaline, new phenolic bisbenzylisoquinoline bases. Yakzigaku Zassiii 87: 793-796. 1967. Alkaloids of menispermaceous plants. 93, Tonm.i., AI., M. JCICHIand II.FURCKATYA. CCXL\?I. Alkaloids of Limacio oblonga. Yakiigakii Zassiii 87: 1560-1561; C h e m . A b s t r . 68: 84980j (1968). 94. LE, S. T. and I. S. CHEN. 1976. Structure of a new bisbenzylisoquinoline alkaloid, lindoldhamine. Heterocycles 4: 1073-1076. 95. ITO,K . 1960. Alkaloids of magnoliaceous plants. XXIT-. Alkaloids of iMiciielia conzpressa. Yakiigeku Zassiii 80: 705-707; Cheni. A b s t r . 54: 18887e (1960). R . and 11. P. GUHA. 1949. The alkaloids of Mahonia acanfliqolia, Sci. 96. CHATERJEE, end Cziltiire 15: 163; Chem. A b s f r . 44: 270Ge (1950). O T L. N . P ~ s o v a . 1971. Alkaloids from plants of the 97. Pan-or, P . P., N . 31. ~ I O L L and Berberidaceae family. D o k l . Bolg. A k a d . A7aztk 24: 6 7 5 6 7 8 ; Chenz. Abstr. 75: 1484652 (1971). R . , 11. P. GVHAand S. K. SEN. 1950. Studies on ~lfaaiioniegenus. 111. 98. CHATTERJEE, Mehonia borealis and ?daiionia s w i o n s i i . J . Ani. Phernt. Assoc. 40: 36-39. R . and If.P. G ~ H I19.50. . Studies on Mahonia genus. I. The alkaloids 99. CHATERJEE, . ASSOC.39: 181-182. of JI. grtfithl. J . A v ~ PhUr???. R . and hl. P. G U H L 1951. Jfahonia genus. IT-. -TI. leschenaulfzz, X. 100. CHATERJEE, nzanzpztrenszs and JI.s~kkzwienszs. J . Ani. Pharrn. Assoc. 40: 229-232. 101. YISG, T. H . 1960. Alkaloids of Berberidaceae. X X I X . Alkaloids of Mahonza lornarzfolia and JI.morrisone)iszs. Yakicgaku Zassht 80: 1304-1307; Cheni. A b s t r . 55: 3005h (1961). 78.
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ALKALOIDS
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102. 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). 103. D O ~ I ~ O T C R.H ,W. and J . E. KSAPP. 1971. -1lkaloids from 3lenisperniztnz c a m d e n s e . Llojtliu 34: 292-300. 104. 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 Xetiisperiiiicni 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. 105. TOMIT.\! A l . , Y. OK.ivoTo, T.SAG.LI, S.T.is~1c.iand T . H.LYATA.1970. Studies on the alkaloids of menispermaceous plants. CCLTTII. -1lkaloids of J~ei~isperiti12z1))z daztricitm DC. (Suppl. 6,. Basic components of Siberian X e u i s p e r i i i i o i > daitricitvi DC. (Lztilos e i i i j e n ~ i kd o u r s k i i ) . Ihkicgaku Zasshi 90: 1182-1186. 106. CH-IS, I(.C.. 11.T. -1.ET-.ISS.C. H. H.~ss.~L and -1.11. K.SISGSTER. 1967. Biosynthesis or’ phenols. Part S I I I . Structural relationships of alkaloids of Demerara greenheart. J . Cliem. SOC.C 1967: 2479-2485. 107. HEARST,P. J. 1964. Greenheart alkaloids. 11. Isolation and characterisation of seven alkaloids. J . O r g . Ciieni. 29: 468-470. 108. TOJIIT.~, 31.; H. FURUKAII-A, T . H. ~ L Sand G T. J. LIX. 1964. Studies on the alkaloids of Loti embryo. (1). Structure of isoliesinine. Tetrahedron h i t . 1964: 2637-2642. 109. CH-IO,I-.:I-.CHOU,P . TASG and C. CHOU. 1962. Alkaloids of embryo Seiitriibo tiucifera. 1. Isolation and characterization of liensinine. S c i . Sinica (Pekiiig) 11: 215-219; Cheni. A b s f r . 57: 7363i (1962). 110. 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). 111. 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 cieillerdii (Moniniiaceae). d z t s t r n l i m J . Cireiii. 26: 455-459. l l l a HART:S . K.: S. R . .JOSES, J . h. LUIBEETOSand H . RES. 1972. -1lkaloids of PachJgone pitbescois illenisperniaceae 1 . -4itsi. J . Ciieiii. 25 10) : 2289-2290. 112. TO\IiT.I, ll.,H. FERELIII-.~, 11.JUICHIand S. L r . 1967. llkaloids of menispermaceow plan-s. CCSLT-I. Alkaloids of Parncjclea ochiaiam. I-trkugakit Zasshi 87: 1255-1287; CIieiii. .i b s f r . 68: 4 6 7 6 k I1968 I. .. .. 113. BRL-CHH.~ESES, F. I-.,A. C. S-~STOS, J. KSABEand G. A. S.~STOS.1957. The structure of phaentharin. -4rcli. Pliariii. 290: 232-250. 114. SASTOS, A. C. 1931. hlkaloids of Piieeoufiiits ebracfeolafus iPresl) AIerrill. Phaeanthine I. Re;!’.Filipine M e d . FariiL. 22: 11: Cheiii. d b s i r . 26: 729 11932). ’ 115. -$SET, F. -1.L., G. K. HUGHES and E. RITCHIE. 1950. The alkaloids of P l e o g y i e cuntiiiigliniitii. ilusfrelietz J . Sci. Research 3.4: 346-3491 Chem. A b s f r . 45: 822i (1951). 116. SIDUMIS! -1.-1.and 1’. S . T ~ H I S T . 1972. S e x hisbenzylisoquinoline a!kaloids from Pjcmrrt’ienii 0i~sfr!1/iam7(llenispermaceae j . .iustrriiinn J . Chem. 25: 2251-2254. 117. 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. 118. LODER,J. W. and R. H. S E . ~ R1972. S . Tumor inhibitory plants. Tn-o new bisbenzylisoqiiinoline alkaloids from Pyniirrlien,z oznnihn (3lenisperniaceae). d u s i r ‘ l h t t J . C5eiu. 25: 2193-2197. 119. T.KIH.~SHI,K., 11.J . MITCHELL and 11. P. C a n . 1976. Sciadenine, a n e v bisbenzylisoquin,Aine alkaloid from Sciadoteiiio tosirere. H e f e r o c j c l e s 4: 471-474. 120. T-IILIHISHI! K. and 11. P . C.i\-.i. 1976. Sciadoline, a nen- type of bisbenzylisoquinoline alkaloid. HeierocFcles 5 ( l ) : 367-371. 121. Tox1T.i. 31. and H. SHIRII. 1942. ;ilkaloids of menisperniaceae. LIT-. Alkaloids of S i e p h n i a capifatn. J . Pliariii. Soc. J a p a n 62: 351-386: C h e w . .Ibsfr. 45: S540e (1951). 122. TAS.II 11.1iozric.i; 11. T.KEUCHIand 11. A 1 ~ c . \ ~ r1969. . 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. I’akugnku Ziissiii 89: 1678-1681. 124. 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). 125. KUPCH-IS, S.ll., IT.L. ASB nd B. S.THY.\G.~RIJ.\S, 1961. llenispermaceae alkaloids. 111. -1lkaloids of Si iia h e r m n d i f o l i n . J . Piiarm. Sci. 50: 819-822. 1%. 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 uZasshi 126s Ref. Ga. p. 2T9. 127. T O ~ ~ I T 11. . ~and , T. I B U K . ~1963. . .Ilkaloids of menispermaceow plants. CCIII. Alkaloids of formosan Stephnniil japonica. 1. Isolation of tertiary bases. I’akugaku Zasshi 83: 996-999; Chenz. A b s i r . 60: 4201h (1964). ~~
\ - - - - I
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[VOL.
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NO.
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128. BARTON, D . H. R., G. W. KIRBYand A. WIECHERS.1966. Phenol oxidation and biosynthesis. Part X I . The structure of stebisimine and the biosynthesis of epistephanine. J . C h e m . Soc. C 1966: 2313-2319. 129. TOMITA, AI. and T. IBUKA.1963. Alkaloids of menispermaceous plants. CCIT-. hlkaloids of formosan Sfepiiaiiia japonica. 2 . Structure of a new tertiary phenolic biscoclaurine type alkaloid, stepholine. Yakugaku Z a s s h i 83: 940-944; C h e m . A b s t r . 60: 4202a (1964). 130. SATOMI,M. 1955. Alkaloids of menispermaceous plants. CXXYIII. illkaloids of Stephenia japonicn XX. Alkaloid with a curare like action; isolation of insularine. A m . R e p ! . I T S U L i L a b (Japun) KO.6: 31-33; Chem. A b s t r . 50: 10112f (1956). 131. TOMITA,11. and H. KSHIKITA. 1944. Alkaloids of hlenispermaceae. L X I X . Alkaloids of Stephania cephera)ztha. 3. J . P h a r n t . Soc. Japan 64: 240-241; Chem. A b s t r . 45: 5173h (1951). 132. TOMITA, A I . , 11.Kozusa and S. Lu. 1967. Studies on the alkaloids of menispermaceous plants. CCXXIX. rllkaloids of S t e p h a n i e telrandra. Yakzcgaku Zassiii 87: 316-318; Ciiem. A b s t r . 65: 32855g (1967). 133. CHOU,T . Q. 1935. The alkaloids of the Chinese drug, mu-fang-chi. Ciiinese J . Physiol. 9: 267-274; CiietFJ. A b s t r . 30: 4716 (1936). 134. KUPCHAN, S.M.,T. H. YASG, RI. L. KIKG and R. T. BORCHARDT.1968. Thalicfrum alkaloids. T?II. The isolation, structural elucidation and synthesis of dehydrothalicarpine. J . Org. C h e m . 33: 1052-1055. 135. SH.IJIM.A,II., R . J . SHIKEand B. S.DUDOCK.1967. Tiialicfrum alkaloids IT:. Three new alkaloids from T . f e i i d l e r i : thalidezine, thaliporphine and preocoteine. Tefralzedron 23: 2887-2892. 136. ~IOLLOJ,N. &I.!7.. ST. GEORGIEV, P. P. P a ~ o vand D. JORDASOV. 1967. Study on the alkaloids of ThalictrirniJoetidit~i~ L. spread in Bulgaria. C. R . Aced. Bidg. Sci. 20: 333-336. 137. ABDIZHABBAROVA, S., Z . F. ISMAILOV and S. Yn. YUKUSOV.1968. $Ikaloids of the roots of Thalictrzim Joeiidztni. K h i m . Prir. Soedin. 4: 330-331; C h e m . Abstr. 70: 75086m (1969). 138. PADILLA, J. and J. HERRAX.1962. Hernandezine-a new alkaloid of the bisbeazylisoquinoline series. Tetrahedron 18: 427-432. 139. PVL.ATOVA, KH. G., S. KH. MAEKH,Z. F. ISMAILOI-and S.Yu. Y u ~ v s o r . 1968. Alkaloids of Tiialictriinz isopyroides. Structure of thalisopine. K h i m . P r i r . Soedin. 4: 394-395. 140. WC, W-K, J. L. BEIL, R-P. LEU and R . W.DOSKOTCH.1977. Alkaloids of Tiialzctrum. XX. Isolation, identification and structural elucidation of the alkaloids of the root of Tlialictrum longistgluwi Lloydia 40: 281-289. 141. WL,W-K. J . L. BEALand R . W. DOSKOTCH.1976. Alkaloids of Thalictruni. XS?. Isolation of two additional alkaloids from the root of Tlialictrztm luciditm. L l o g d i e 39(5): 378-379. 142. DL-TSCHEKSKA, H. S-., A . I-.GEORGIEYA, S . AI. MOLLOV, P. P. P m o r and N . K. KOTSEV. 1971. Phytochemical study of Tiialictricwi minus L. Dokl. Bolg. A c a d . Xaiik 24: 467-470. 143. MOLLOV, N . M,, P. P . P a s o r , THLASLE SHAT and L. PAKOT-A. 1970 Alkaloids of Tiialictriirit rzigosuni, T . aqiiilegifoliztnz and a form of T . minus. Dokl. Bolg. A k a d . Xaick 23: 181-183; Ciiem. A b s t r . 73: 32285v (1970). 144. Yvsusor, S. and h’. S . PROGRESSOV. 1950. Alkaloids of Ranunculaceae 111. Alkaloids of Thelictrzcni mimts. Zhicr. Obshcliei Khim. ( J . G e n . Ciiem.) 20: 1151-1lGl: C h i . A b s f r . 45: 1608c 11951). --, 144a. LIAO,TT-TT,JT L. BE.\L, W-S.WL- and R . 1%’. DOSKOTCH.1978. Alkaloids of Tlmlictrztm XXT-I. S e w hypotensive and other alkaloids from Thalictruni ?iiiiizts Race B. Lloydia 41(3): 25i-270. 145. WALI, B. K., S-. P . A ~and L K . L. HASDL 1964. -4lkaloidal constituents of Thalictrunz I n d i m J . P h a r n i . 26: 69. p e d i ~ i i c ~ t l e t i tEdgeT. n~ 146. WU, TV-X., J. L. BEAL,R-P. LEU and R . W.DOSKOTCH.1977. Alkaloids of Tlialictrum. X X I . Isolation and characterisation of alkaloids from the roots of Thalic!ritm podocurpiim. Lloydia 40: 384-394. 147. SHAMMA, 11.and S.T.TAO.1973. Thaligine, a ne-- bisbenzylisoquinoline alkaloid from Tiiil!ic!ririii polyguiiiirm Nuhl. (Ranunculaceae). E x p e r i e v i i a 29: 517-518. 148. R r , W - S . , ,J. L. BE.IL and R . W.DOSKOICH. 1977. Alkaloids of,Thalictrzrm. X X I I . Isolation of alkaloids with hJ-potensive and antimicrobial activity from T’iialictrztm rerolzttztiii. Lloydin 40: 508-514. 149. FOKG,, H. H. S.,J. L. BEALand 31. P. CAT-A. 196G. Alkaloids of Tlinlictrmi. 1-11, Isolation of alkaloids from the roots of Tiielictrtini rociiebrzrnian~tni. Lloydia 29: 94-100. 11. P . Cava and J . L. BESL. 1976. Thalibrine and nor150. Sa.i, J. RI., A I . J . MITCHELL, thalibrine, new bisbenzj-lisoquinoline alkaloids from Tiialic!rirm rociiebr~tnia?ilil)~. Heterocyc’es 4: 753-757. 151. SA.\, J . 31.,11.I-.L~I;SH\lIK.\STHA\I, hI. J. ~IITCHELL, AI. P. Cars and J. L. BEAL. 197G. Thalibrunimine. a n e x iminobisbenz\” lisoauinoline alkaloid. Conformers of thalsimine. _ Tetraliedro?~Let;. 1956: 513-516. \-
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GTHA ET AL.
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B I S B E S Z I ~ L I Y O Q U I S O L I S EALKSLOIDS
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152. ~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. L l o j d i n 35: 167-1?6. 152a W r , W-S..J. L. BEIL, E. H. FAIRCHILD and R . W . DOSXOTCH.1978. Six new blsbenzylisoquinoline alkaloids from Thalictrunz rugosicni. J . Org. C h e m . 43: 580-585. 153. NITSCHER, L. .4.,W-X. IVv and J. L. BEAL. 1972. -4ntibiotics from higher plants. Thalictrunz rugosum. Thalrugosamine, a nen- bisbenzylisoquinoline alkaloid active W. Myc-obncteriu ni smegma tis , E x p e r ien tie 28 : 500. 154. Wu, W-S.,,J. L. BE-IL,G . W.CL.IRKand L. A. MITSCHER.1976. Antimicrobial agents from higher plants. 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, 155. ?IIOLLOV, S . AI. and I-.ST. GEORGIET.1967. Secondary alkaloids of Thalictricm s i m p l e x L. C. R.A c e d . Bitig. Sci.20: 329-332. 156. MAEI\H.S. KH.. Z. F . I ~ M ~ I L and OV 8. Yu. I-L-ST-SO 1968. Thalsimidine. a ne-bisbenzilisoquinoline alkaloid from Tlialic~ricnis i m p l e x . Khin7. Prir. S o e d i x . 4: 138. S. KH. and S. T u . T u s r s o v . 1965. Structure of thalsimine. K l k . Prir. 157. XIEKH, Soediii. 1: 188-194; Cliem. -4bsir. 63: 14929e (1965). S.,5.K H . XLEKH and S. T u . l u s v s o r . 1978. *ilkaloids of Tiiul 5 i a ~IBI)IZH.IBB.~RO~-.I, lictruni sul:nnabandense. Khini. Prir. Soediil. 1978(1): 139-110: Cheni. -4bstr. 89: 39368~ i1978;. 158. Ft-JITA, E.. T . TomxiTsu and I-.K.\so. 15162. .Ilkaloids of Thiilictruni !lizcifbcrgii I X . Structure of thalicrine and homothalicrine, the tertiary bases of the root. Elklcgeku Znsrlii 82: 311-315. 159. FCJIT.~, E.: T . TomxkTsr and 1.K1T.nfvR.i. 1964. Alkaloids of Timlicfricm tiizc7ibergii D C . S T - . The identity of thalicrine with aromoline. Bull. Iizsi. Cheni. Res. 42(4): 235245: Clieni. .ibsir. 62: 5310 (1964). 160. FL-JITA, E . and T . T o m x u s r . 1959. A1lkaloids of Tliiilictrzrnz thunbergii. I-. Structure of thalicberine and 0-methylthalicberine, tertiary bases in the stem and leaves. I’akicgoku Zasshi 79: 1256-1260; C h e m . .ibsir. 54: 4642h (19601, 161. Tomif.ITsu~T. and 11.S.IS.IK.ITT-.I.1975. Studies on the alkaloids of Tlmlictrum thenb e r g i i DC. ST-111. Structure of thalictine, thP tertiary base in the stems and leaves. C/i~?n?. P h m . Bull. 23: 2279-2283. 162. DTT-LXI-B.II)~,D., J . S.K . -4i-Ix>S . T.FIAGBE, A . S . TACPLIE, J. E . KKIPP,D. J. SLATXIS and P. L. SCHIFF,J R . 1976 Constituents of West l f r i c a n medicinal plants. XT-. Dinklacorine, a new biphenyl dibenzodiosin alkaloid from Tiliacorn d i ~ i k l n g e i . L l o y d i a 39: 213-217. -4.S . ,D . Di\-c.zi.i-B.iDr, .J. S.K . AYIM,T . T. DIBR.~,J . E. KSAPP,D . J. SLATXIS 163. TACKIE, and P. L. SCHIFF,.JR. 1975. Constituents of West-lfrican medicinal plants VII. hlkaloids of Tiliticora diiiklilgei. Lloydiii 38: 210-212. E , S . ,D . Dn-u\r.\-B.iDr, J . E. KS.\PPand P. L. SCHIFF,JR. 1973. The structure 164. T - ~ C K I-1. of funiferine, a biphenyl alkaloid from Tilincorn f i i i i i f e m . L l o j d i a 36: 06-71. 165. DTn-x\-B.mu, D., T . U. OKARTER, A . S . T.\cI~IE, J. A. LOPEZ,D. J . SLATXIS, J. E. Ks.IPP and P. L. SCHIFF,J R . 1977. Constituents of TF-est -4frican medicinal plants. S I X . Funiferine -\--oxide, a nen- alkaloid from Tilincore ,fzcii-lisoquinoline alkaloid from Ti!i,rcora rocenloso. Tetr~ilrcdroiiLei?. 2-41. B . , T . R. C;OT-ISD.~CH.LR THE, S . T-I~TT-ASATHAS! K. W .GOPISATH 169. ASJ.~SEI-L-LL-, and B. R. PAI. 1969. -1lkaloids i;f rnceniosn Colebr. Te?ruhedron 25: 30013105. 170. R.io. K. T-. J . and L. R . Ron-. 1959. S e x alkaloids from Ti:iacorn raceiiiosa Colebr. Part 11. Isolation of tiliarine. J . S r i . Ivd. R E S .(Iiidinl 18B: 2iT-249. 171. TACKIE:-1.S . . D . Dwt-xi-B.mu, T . OILW.TER.J . E. KS.LPP,I). J . SL-ITKISand P. L. SCHIFF..JR. 1971. Constituents of West -1frican medicinal plants 11. The isolation of alkaloids from selected Triciisin speciey. Llordia 37: 1-5. D . , J . 3 . K . - 1 i - n r . -1.S . TACKIE,11. -1.ELSOHLI?J. E. Ks.~PP,D. J . 172. DTT-TX.I-B.IDL-, SL.LTI~IS and P. L. SCHIFF.Ja. 1975. Constituents of West African medicinal plants. S I I . Trigilletiniine, a nex- bisbeiiz!-lisoquino!iIie alkaloid from Triclisio spec:es. E@ e r ie > I i ia 31 : 1251-1 252.
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