THE SPIROBENZYLISOQUINOLINE ALKALOIDS RUTHMARIEP R E I S ~and E RMACRICE SHAMMA* D e p a r t m e n t of Chemastry, T h e Pennsylrania State Cnzr ersit? , l-niierszt> P a r k , Pennsjlranaa 16802
1, IsTRoDUCTIOS.-TwentJ--nine spirobenzylisoquinoline alkaloids are presently known. They all possess the spirobenzylisoquinoline nucleus represented in expression I. A methylenedioxy group is aln ays present at C-9, 10;C-2 and 3 are inevitably oxygenated. bearing hydroxyl, methoxyl or methylenedioxy substituents. S o norspirobenzylisoquinolines are knon n to occur naturally; rather, the nitrogen atom is tertiary and bonded t o a methyl group. Spirobenzylisoquinoline alkaloids have been found only n it hin the plant family Fumariaceae. More specifically, they occur n ith one exception, within the genera Fumaria and Corydalis. There is a report of the iqolation of ochotensine from Diceiztra cucullaria Bernh. nhich also belongs to the Fumariaceae (2). 2. RELATIOSiHIP BETWEES PLAST SOURCE I S D SUBSTITTTIOh PATTERS O F RISG c.-A direct relationship obtains betn een the plant source and the oxygenation pattern of ring C. The genus Fumaria yield3 spirobenzylisoquinolines bearing only one oxjgenated substituent in ring C in the form of an alcohol, a n acetate, a methoxy ether. or a ketone located at C-S. On the other hand. thoie bases originating from Corydalis speciec pos;ess tivo oxygenated Yubstituents in ring C, ucually in the form of t n o alcohols or an alcohol plus a ketone. I n those case; where an alcohol and a ketone are present. the alcohol is positioned at C-S n hile the ketone is at C-13. The alkaloid fumarofine (26) is unusual in that It is found in Ftimaria qpecieq. j e t it incorporate; a ketone at C-S and a n alcohol at C-13. Fumarostelline. isolated from F . rostellata Knaf (29), i c almost certainly identical n i t h funiarofine (26) so it ha not been giyen. here. a separate identity. Therr is also a \mall group of qp obenzylisoquinolines. concisting so far of ochotensine ( 2 T ) , ochotenci (28). and raddeanamine (29). found niobtly in Corydalis species, n-hicli pos n exocyclic nietlij lene or a methyl plu. an alcohol at C-13. I n thi; instance. no oxygenated substituent iq found at C-8. 3. AkBsOLUTECOYFIGURATIOS A S D R IcE~iIz.~TIos.-The absolute Configuration of the spirobenzy1i;oquinollne alkaloids n-as first considered n ithin the context of the aromatic chirality rule (+j-Ochotenqine (27). (+)-ocliotenqimine (28), (+)-ochrobirine (18). and dihj-drofumariline (11)and, b>-extension. (+)-fumariline (10) were thus shonn to posse the abcolute configuration denoted in expres-ion I above (3a, b). These concl ons nere further supported b\ a complete x-raj study of ochrobirine methanolate (4).
I
For the sake of simplicity, all the spirobenzylisoquinolines have been dran-n here in an absolute configuration corresponding to expression I. It must be borne in mind, however, that this could eventually prove not to be the case. 305
30G
JOCRSAL OF KATURAL PRODCCTS
[VOL.
43, so. 3
Spirobenzylisoquinolines possessing both a ketone and an alcohol in ring C can undergo racemization through a series of base-catalyzed retro aldol condensations followed by recyclixation. Such racemization has been shown to occur in t i f r o in the conversion of sibiricine (21) into corydaine (25) (6a, b). It must also account for the fact that raddeanone (20) is known only as a racemate, n-hile yenhusomidine occurs either as the levorotatory isomer (23) or as the racemate (24). The alkaloid raddeanine possesses two alcoholic functions in ring C and is found both in the dextrorotatory (13) and the racemic (14) forms. I t is likely that its precursor, raddeanone (20), must have undergone epimerization by a retro aldol cleavage, followed by aldol recyclization and reduction to yield a racemate. 4. BIoGENEsIs.-Depending upon the substitution pattern in ring C, somewhat different pathways for the biogenesis of the spirobenzylisoquinolines may be postulated. If an exocyclic methylene is present a t C-13, the precursor is likely to be a C-13 methylated dihydroprotoberberine S-metho salt. Such a salt can rearrange to a spiro structure via the intermediacy of a quinone methide, if phenolic groups are present in ring D (7); or by a photo-induced process, if no phenolic groups are available (8). Those spirobenzylisoquinoline alkaloids possessing one or two oxygenated functionc in ring C must originate from a protoberberine salt oxygenated or, at least, unsaturated in ring C, although the essential details of such a rearrangement still remain to be established (9a,b; Ga,b). They definitely are not formed through the intermediacy of a spirobenzylisoquinoline precursor possessing an exocyclic methylene group in ring C. 5. GEKERALREMARKS COSCERSISG THE TABULATIOS.-A~~ uv data are in nni, and log E values are quoted between parentheses. Ir frequencies are in cm-'. In several cases, the interpretation of a pmr spectrum has been slightly modified from that given in the original paper. TYhenever two or more references are cited for a pmr spectrum, the first one is the one actually shown in the accompanying diagram. The coupling constant between H-11 and 12 is not quoted since it is consistently in the order of 8 Ha. If some other coupling value is not given, it is usually because this information is lacking in the original literature. Applications of the nuclear Overhauser effect to the spirobenzylisoquinolines have been discussed in detail in the literature (10). Cmr chemical shifts with identical superwipts are interchangeable. 1. FUMARITINE
CzaHziOjS: 355.1419 KIP: 157" (dry ether) (11);157-159" (12) [ a ] ~S:. A . UT: (EtOH) 287 (3.83) (13a) IR: (CHCl,) 1100, 1275, 1590, 2880, 3550 (11): (CHC13)3540 (15). See also (13a lH XMR: (CDC13) (16, 14, l a , 17. 15); (CFKOOH) (17) 13C XMR: (CDCl,) (14) MS: 355 (hIL), 340, 324, 206, 192 (18, 16) C D : AE~,,,-8 96,m, -2.68277, +3.5823, (63). SOURCES: F m i a r z n oficznalzs L. (11) Fmiarza schlezcherz Sover-Willem
MAI-JUS
19so]
PREISXER E T AL.
:
SPIROBEXZYLISOQGISOLISE ALKALOIDS
307
2. F U U A R I T I N E A'-OXIDE
MP: 204" (lOyGMeOH in C6&) (14)
[Q']D: 1 . A . UT-: SA. I R : 2500-3500 (14) 1H S M R : (DMSO) (14) 13C S M R : ( D 2 0 + 2 drops 40% S a O D ) MS: 3i1 (MT),192 (100) (14) SOURCES: Fziniarrn k r i i l z k i i Jord. (14,
3. F U l I h R I C I S E
CelH230j: 369.1576
MP: 177" (MeOH) (20) [a]D:
-31" (c=O.g'i CHC13) (21)
UI-: (EtOH) 207 (4.74). 235 (3.94), 2888 (3.74) (21, 16): 1EtOH) 286 13.81) i13b)
I R : (CS2)3560 (21. 16, 221, 3600 (23). See also il.?h).
1H 9 L l R : (CDCiS)-(la,22) 31s: 369 (M+), 354, 338, 220, 206 ,140 (18,16) SOURCES: Fziniaria officinalis L. (20) This alkaloid is probably identical Kith 0-methvlfiimarophycinol found in Herba Fumaiiae Officinalis (36).
C22H2806S:
39i.1525
LIP: 107-109" (AIeOH) (24) [[,'?~OD: ]?OD: -67.5' ( c = l $ CHC13) (24) L-T-: 290.ix (3.88) (24) - 881 _., 124) ~I R : 1730, 3500 124) 'H S l I R : 1CDC13j ( 2 5 , 24J (AI+) (251, 355 126). (26), 354 354-(100), (481, MS: 397 fAI+) 1100). 337 (481, ~. 125). . .. 322 (23), 192'(6) 322'(23), 192 (6) i25,18) (25; isj' o-ficrmlis L. (24, 26) SOURCES: Firniurie o-ficimlis
5.
0-AIETHYLFCAlhROPHYCIXE
LIP: 124-126" (24). 124-127" (ether-NeOH 1 (36) ~ Q ' ] z 2 D : -51" (C=27$ CHC13) (36) SOURCES: Fzmurzc o-ficznalzs L. (24, 27, 36)
The reported concentration of 27cc
(CHCL) for the measurement of the spe-
cific rotation is suspect.
308
JOURS.4L O F S A T U R A L P R O D U C T S
6. FUMARITRIDIXE
[VOL.
43, NO. 3
C2iH230jx: 369.1576 MP: 198-200" (EtOH) (28, 29) CHC13) (28, 29) [aI2*D: +18" UT: (CHC13) 215 (3.73), 230 (3.70), 285 (3.48) (28)
(~=lx
I R : S.,4. 'H XRIR: (28)
>IS: 354 @I+) (loo), 338, 337, 192 (28) SOURCES: Fitniarie rostellata Knaf. (28, 29)
fi
7. FURIARITRINE
....3
*...CH
N:-.
-
oc:,;r: 3 3 1 5
Cb3 i 115
::
y w I
=n>
YIP: [.ID:
383.1732
153-155" N.A. (EtOH) (28, 36)
IR: S.AA. lH S M R : (28) RIS: N.A. SOURCES: Furnuria rostellata Knaf. (29) Furnuria oficinelis L. (38, 36)
O;-s
6.93,
C22H2jOJi:
Hz
The presence of an aromatic singlet protonasfar downfield as 67.11 isunusual.
8. PARFUMINE
C2"HigOjN: 353.1263 e
N:
;@ ; -
.....
0
1.415
ci,
RIP: 111-112" (EtOH) (30); 118-119" (RleOH) (31); 118-120" (EtOH) (62); 118120" (CHC13) (29)
:eo
$116
OL
( ~ , 6
i ' l i
9. PARFUMIDIXE
C2iH210jN: 367.1419 S.,,d
: ;* 6.125
Ch,
1.71s
UT-: [cY]'~D: (EtOH) +18"+1" 235( c(4.42), = l . l CHCl?) 260 (4.10), (30) 290 s h , 358 (3.42) (30) I R : 920, 1030, 1505, 1610, 1710, 3100, 3420 (30); (CHC13) 1710, 3545 (62) 1H NMR: ICDCld 130 130a) 11s: -353 (li+),538, $24,'308'(30) CD: hnm +1.4135a, --1.762c3, -6.36239, $1.18239 (63). SOURCES: Firmarzu kralzkzz Jord. (19) Funiarzn par;ij?ore Lam. (30, 31) Ficnrarza rostellntn Knaf. (29) Funrnrzn ;nzllnntz? Lois. (62)
1.215
LIP: 170-171" (RIeOH) (32): 171-172" (EtOH) (62); 169-171" (RleOH) (31) 165168" (ether) (36) [(Y]*'D: -33.3" ( ~ = 0 . CHC13) 5 (32) U T - : 235 (4.46), 263 (4.14), 290 sh, 360 (3.40) (32). See also (62). I R : 915, 1020, 1520, 1620, 1720, (32); (CHCla) 1705 (62) lH S R I R : (CDCl,) (32) (32a) SOURCES: Funinria purriflore Lam. (32, 31) Firniaria o-fici?ialis L. (36) Firnraria mi:lantii Lois. (62) ~
N:.
... 0 OCH,6 1 3 s l.Ils
s
:'s
MAT-JUS
19801
PREISNER ET AL. :
SPIROBESZYLISOQUINOLINE ALKALOIDS
10. F U M A R I L I S E
CsoHI,O&:
309
351.1106
MP: oil (33); 138" (hleOH) (11); 74-76" (AIeOH) (29); 144" (CHC13-hleOH) 134); 141"-143" (EtOH) (36) C138" ic=l.05 CHC1-i) 121): 1 9 6 " ( ~ = 1 . 0
[ff]D:
" I
\ - - I
: T67" ( c = - l 5 i CHC13) (33) [cY]'~D : +82.5" (c=O.GS CHC13) (36) [ff]*'D
L-1-: IEtOH) 203 (4.80). 237 14.311, 263 14.05), 294 13.66), 355 13.51) (16, 21); (EtOH) 236 (4.38), 262 (4.01), 293 13.68), 352 (3.51) (13c). See also (34, 33). (CHCL3j 1109 (16, 21); 1710 (36): (Sujol) 1638, lT05, 1730, 3390 (33). See also il.1r1.
IR:
FzL?12nria o_tTicz?lalisL. (11, 36) Fzriiiaria rostellate Knaf. (29)
11. DIHTDROFUALiRILIXE
C2OH1c.OjS: 353.1263
AIP: 129-133' (ether) (16) I R : SA.
'H
slm:
(CDCl;) (16j S o t a natural product, but obtained from LiAilHIreduction of na:urallv occurring friinariline.
I
'
12. L E D E B O R I D I S E (Ledehouridine)
C2.,H210&: 371.1369 NP: 140-141" (35) +114" ( ~ = 0 . 2 81IeOH) (35) S.A. I R : 920, 1030, 1500, 1600, 3430, 3540 (35) 'H S l I R : (CDCls) (35) AIS: 371 (AI-), 353,338,324,308,291, 192,190, 177 135) SOURCES: Corydnlis ledebourintia K. et K. 135) -a]D:
CY:
C91H2306S: 385.1525
MP: 200-202" (acetone) (36, 37): 204-205' (acetone) 135) +7!;4' (c=0.11 MeOH) (26, 3 7 ) + l o / (c=0.18 JIeOH) (35) S.A. I R : 920, 930, 1040, 1515, 3520, 3540 135): (CHCI,) [a]**D: [a]D:
n-:
3,590 (26. 37)
H S A I R : CCDCl,) (26, 35, 37, 1 7 ) (CFXOOH) (17) MS: 385 (11-1) 370,367, 352, 338,324,308, 206 126, 35, 37 ) SOURCES: Corydelzs ochofensis Turcz. v a r . raddeniia (Regel) S a k a i (26, 3 7 ) 1
There is also another alkaloid k n o m bv this name, see Kh. A . rislanov and A. S: Sadykov, J . Gen. C h e m . CSSR, 26, 579 (1956).
JOURXAL OF KATCRAL PRODUCTS
310
C2iHwOJi:
14. (+)-RADDEANIKE
[VOL.
43, NO. 3
385.1525
MP: 219-220" (hIeOH-CHC13) (35) [a]D: 0" (35) Remaining physical properties resemble those for (+)-raddeanine. SOURCES: Corydalis ledeboitriana K. e t K. (35)
C2&2507:I\;
427.1630
RIP: Oil (26)
(c=0.52 MeOH) (26, 37) [ a I z 0 ~f82.7" :
UV: S . A . I R : (CHC1,) 1740, 3580 (26, 37) 'H SRIR: (CDC13) (26, 37) &IS: 427 (hI+), 384, 367, 352, 338, 324, 322, 308, 206 (26) SOURCES: Corydalis ochotensis Turcz. var. raddeana (Regel) Kakai (26, 37)
C ~ O H ~ ~ O369.1212 ~N:
16. SET*ERZIR'INE (Sen-ercinine)
MP: 90-91' (EtOH) (38) [a]D:
+log" ( ~ = 1 . 2CHC13) (38)
UT-: (EtOH) 290 (4.04) (38)
I R : 930. 1050. 1490. 1510. 3400 138) 1H S M R :
f38)
LIS: 369 (?.\r+); SOURCES:
17. YESHUSOMINE 5
CtiH2306N: 385.1525
MP: 127-128" (decomp.) (MeOH) (39,40)
52bl 5
+48" (c=1.0 hIeOH) (39, 40) (EtOH) 241 (4.11), 288 (3.86) (38, 40); min: 236 (4.10), 261 (3.08) (40) I R : (Sujol) 935, 1030, 3300,3480 (39,40) 'H S l I R : (CDC13) (39, 40) KMR: (41) >IS: 385 (?(I+)(39) SOURCES: Corydalis ochotensis Turcz. (39,40) [a]"D:
UV:
6
,os
CH
3 I (ili
3 s*g
'
336, 322 (loo), 292, 190 (38) Corydalzs se7uerz07uz Regel (38)
I "'c
.I=>H z
31.11--JUB
1%0]
P R E I S S E R ET AL.
:
SPIROBESZTLISOQUISOLIBE -ILK-lLOIDb
CmHigOJ.
18. O C H R O B I R I S E
311
369.1212
MP: 198" (solvent free) (42, 431: 204" (EtOH) ;.;*1~:
[?,*OD:
LV
IC
(44). Diacetate 179" (44); Methanolate 138-139" (42, 43) f36.9" (c=O.4 CHC13) (42) +36' (c=1.8 CHCl,) (42) (MeOH) 205 (4.80), 240 (3.94), 291 (3.91) (45). IEtOH) 201 (4.21), 239 (3 91), 291 (3 87) (46); (EtOH) 205 (4.81), 240 13.94), 250 (3.91) (44). (EtOH) 228 sh 14.36), 291 (3.87) (3a) See also 113d) ICC1,) (45). CHC1,i (23) 3300, 3585, (paraffin oil) 3450, 3530 (44). See also I 13d)
'H S N R . (CDCl,) (45, 44) 13C?U'l\IR. ICDClQ1141) 11s: 369 (1IL),3g4, 361, 336, 322, 293, 265, 204, 190 (18,. 369 (&I-),206, 192, 190 (A'l i--
I
X-Ray: Ochrohirine methanulate (4) SOLTiCES, Corjdalis iictea 1L.) DC. 142) C o r j d n l i s ochroieuca Koch (43) Corjdalzs szbzricn (L.) Pers. 147) CorTdalis ;agzncins Roj-le (44)
19.
LEDEBORISE (Lederbourine, ledehourine)
C2nHl,06S: 371.1369 MP: 184-185" ICHC13-MeOH) (17) ia]D:
s..k.
UT-: (1IeOH) 238 (4.38), 293 13.981, 3.16 (3.90) 117)
I R : 920, 1040, 1600, 1705,3150 (17) 'H S l I R . (CFsCOOH) (17)
11s: 369 (lI-) (loo), 354, 338, 206, 192, 177 (17, SOURCES: Corgdnlis ledebourianu K. et K. 117) Structural assignment mav he in erp i r . For an alternate structire, see F. Santavj. in R . H . F. Manske's The .llkai d s , 1-01. S Y I I , p. 502 (1979).
20.
RADDEANONE
C2iH21OJ .5 , c
383.1369
MP: 168-170" (acetone) (37): 132-133" (acetone) (26 I 0" (c=0.085 MeOH) (26, 37) UT-: (EtOH) 238 (4.58), 289 (4.12), 313 ( 4 0 6 ) (26, 37) I R . (CHC13) 1720,3570 (26,37) 1H S l I R : (CDC13) (26, 37) [.]*OD:
13C S & l R : (CDClz) (41)
MS
383
(M+), 368,352,338,324, 208, 206 (26, 37 1
SOURCES:
CorTdalzs ochotensis Turcz. var. rnddeuna (Regel) S a k a i (26, 37)
OF NATURAL PRODUCTS JOURNAL
312
[VOL.
43,
NO.
3
CioHiiOsN: 367.1055
21. S I B I R I C I S E
!?
M P : 225" (CHCl3-RleOH) (48) [a]D: S.A. UI*: 205 (4.80), 240 (3.94), 291 (3.91),313sh (3.993 (48, 49) I R : (CHC13)1710, 3560 (48, 23); (KBr) 1700 (48) 1H SRIR: (CDCL) (48, 17) 13C S 1 I R : (CDC13) (41) hIS: 367 (11-)(loo), 352, 338, 322, 295, 266, 206, 190 (18) X-Ray: ( 5 ) SOURCES: Corydalis ledebouriana K. et K. ( 5 ) Corydalis sibirica (L.) Pers. (48)
... .
CzoHigO6N: 369.1212
22. CORPrlIKE
LIP: 204" (EtOH) (50) [ a ] D : S.A. UT-: (EtOH) 242 (3.4), 298 (3.3), 315 (3.4) (50) IR: (CHClJ 1516,1601,1633,1707,3260,3560 (3) 'H S h I R : (CDCl:) (37, 50) 11s: 192 (50) SOURCES: Corydalts paceoskii N. Busch (50) 23.
C21H2106K: 383.1369 RIP: 220-221" (RIeOH) (51)
(-)-TENHUSORIIDIKE (1-0-Methylcorpaine) 3
320
L.ilj 1.2
ti,
[ a I z 2 ~ -36.7" : (c=0.44 CHC13) (51) UI-: (EtOH) 204 (4.80), 240 (3.94), 291 (3.91), 313 (3.99) (51) I R : (CHC1,) 1700, 3260 (51) 'H S R I R : (CDCl?) (51) MS: 383 (11-) (loo), 368, 338, 206, 191.5 (h>I++), 190, 177 (51) SOURCES: Corydalis mginens Royle (51)
This alkaloid was originally labeled 1-0-methylcorpaine. I t is simply the levorotatorl- isomer of (+)-yenhusomidine which had been described previously in the literature. 24. (+)-YENHUSOhIIDIPu'E MP: 240-241" (acetone) (39, 40); picrate 214-215" (decomp.) (39, 40) [ a ] * @ D : 0" (C=o.41 CHC13) (39, 40) (EtOH) 207 (4.40), 238 (4.21), 290 (3.74), 314 UT-: (3.i2) (39, 40); min: 222 (4.01), 258 (3.201, 303 (3.64) (40) I R : (Sujol) 931, 1041, 1706, 3275 (39, 40) 'H S M R : (CDC13) 139, 40) 13C S R I R : (CDC13) (41) SOURCES: Corydnlzs ochotensis Turcz. (39, 40)
Mhl--JUS
19801
P R E I S S E R E T -4L.
25. CORTDAINE . ./_
26. FUlL4ROFIXE
SPIROBESZI LISOCJUISOLISE SLKALOIDS
CzoHiiO&: 367.1056 MP: 184" (EtOH) (23); 189-189.5' (ether) (51 I [ C Z ] ~ ~ +l45' D: ( ~ = 1 . 3CHC13) (51) U T - : (EtOH) 236 (4.49), 290 (4.04), 314 (4.03) ( 2 3 ) I R : (Paraffin oil) 1610,1638, 1710,3050,3200 ( 2 3 ) . (CHC13) 3265 (23) 'H S l l R : (CDC13) (23) 13CY l l R : (CDC1,) (41) US: 367 (11-1,352, 338, 322, 190 (23) SOURCES: Corydalis pacsoskii N . Busch (23)
C2oHigOtjS: 369.1212 M P : 255' (lIeOH-CHC& ( 2 0 ) . 266" (decomp.) illeOH-dioxane) (darkening at 240-245") (20); 256" (1leOH) '20) [.ID
The oxygenation pattern of this alkaloid in ring C is unique. The alkaloid fumarostelline, found in F . rosteilnta Knaf., a a s originall?- assigned a structure corresponding to either corpaine or ledehorine (29). Its physical constants, hon-ever, indicate it t o be identical with fumarofine. 27. O C H O T E S S I S E
h.:.
.....
\ -C
I
cci,
313
/
S..%.
U\ : ( E t O H ) for 0-methylfumarofine 208 (445j, 235 (4.35),259 (3.96), 286 13.371, 350 (3 40) (49) I R : 1700, 3460 149) 'H S l l R ID3ISO-de) (49) 1lS. 369 (AI-) (loo), 334, 311, 326, 324, 298. 284, 204. 192 (49) SOURCES: Firniciria kralzkzz Jord. (14) Funiorzn oficinalzs L. (20)
Alp: 247-250" (CHC13) ,(52); 250-251" ICHCl,! 137): 252 (CHC13) (53): 248(AIeOH) 147) o r (",OH) (53 .cY]*@D: +51.0" (c=O.O98 CHCl5) 137) :a]*'u: +51.TC (c=0.2 CHC13) (53) -cyjZ3D: +63.9" (c=2.00.1 s HCl) 1% VI-: (EtOH-dioxane) 284 (4.04) (3a, 3 7 ) : (lIeOH) 290 14.26) (54): (EtOHI 226 (4.41 I , 287 14.20) (55): (EtOH) 226 (4.49), 285 14.18) (13d) IX: iKBri 1605, 1645 (54, 55, 1650 sh 154). See also (13d'i. 1H S N R : >-..I. 11s: 352 (24), 251 ()I-) (1001, 350 (501, 349 1481, 348 ( 2 2 1 , 336 (24), 334 (16 , 3'33 (lo), 322 ( 2 4 , 321 (121, 320 1261, 308 110). 306 114). 305 f l 4 r . 191 116). 190 1181. 189 116,. 176 I161. 148 1341, 103 (16), 102 r l G i , 99 1 6 1 , 94 122), 83 (14), 78 ( l i ) ,77 (16 , 76 1141.65 (12), 63 (14) 154) S - R a j Ochotensine methiodide (56, 5 7 ) SOURCES. Coridalzs ochotenszs Turcz. (53) Corj'dolis ociiofeiiis Turcz. v a r . rndd e m o (Regel) S a k a i ( 3 7 ) CorTdalis sibirice (L.) Pers. (47) Corydalis solidn (L.) Sn-artz (32! 5% Dicepitrn cicciillaria Bernh. (2)
JOURNAL O F SATURL4L PRODUCTS
313 28. OCHOTENSIMIKE
[VOL.
43, s o . 3
CZ1Hz3O4N:365.1627 RIP: Oil (52, 59); Hydroiodide 190" (54); 189-190' (decomp.) (40); methiodide 225" (decomp.) (ether-MeOH) (e53); perchlorate 172" (54) [ a I z 2 ~+49.2" : (c=O.2 RIeOH) (53) [ C Z ] * ~ D : $46.3" (c=0.51 MeOH) (37) UT-: (MeOH) 220 (61). 226 (4.41), 287 (4.12) (54) I R : 1613, 1629 (54) 1H KMR: (CDC13) ( l a , 61, 54, GO) I3C SRIR: (CDC13) (41) hIS: 366 124), 365 (AI-) (loo),36-1 (40), 363 (14), 350 (18), 337 (lo), 336 (18), 334 (lo), 205 (lo), 148 (16), 85 (50), 83 (24) (54, GO) SOURCES: Corydalzs ochotenszs Turcz. (53, 47, 39, 40) Corydalis ochotenszs Turcz. var. raddeana (Regel) Nakai (53, 26, 37) Corydalzs solzda (L.) Swartz (52) CZ2Hz5O5S:383.1732
29. R ADDEAKAnIINE IPlbl
RIP: Oil (26, 3 7 ) +166" (c=0.68 AIeOH) (26, 37) [CZ]~OD: UT-: S.A. TR: ICHC1,) 3240 126. 3 i ) -~ 1H NLFR: ("CDCl,) (26, 37) 368, 365, 206 (26, 37) RIS: 383 (M+), SOURCES: Corydnlzs ochotenszs Turcz. var. radd e a n a (Regel) Kakai (26, 3T)
111.
NOTEADDED TO PROOF.-A recent reinvestigation of Funzaria p a m f l o r a Lam., which is now believed t o be identical with F. indzca (Haussk) Pugsley, has yielded parviflorine (30), the first glycosidic spirobenzylisoquinoline alkaloid (63). Acid hydrolysis of 30 yields (+Iparfumine (8). The sodium borohydride reduction product of 8 corresponds in all respect t o fumaritine (1). The cd curve of fumaritine (1) shows a positive Davydov split between 277 and 294 nm so that the absolute configuration of this alkaloid is as indicated in expression 1. I t follows that (+)-parfurnine (8) and the chemically related (+ j-parfumidine (9) also possess the absolute configuration indicated in expressions 8 and 9 (63). The recorded cd values in methanol are as follows C26H2JXOio: 515.1784 MP: 230-232" (MeOH) (63) [.ID: $1" (e 0.0124 hleOH)
30. PARVIFLORINE
; ;&
UT*: (MeOH) 233 352 (4.50), (3.66).260
.....
h:.....Ck
-
e,>>,
cip
,,.%
?-,>-ci. : c o ~ e
I '1?:
Anomeric proton doublet at 65.35 (J=7.3 Hz)
(4.18), 288 sh (3.701,
I R : (KBr) 1700, 3390. 1H S l l R : (Pyridine-dj). 11s: 515 (&I-), 353, 338, 325, 324. C D : Atnm +l.94s55, -4.6221.3J-18.28261J +4.62~,0. -4.38*29. SOURCES: Fun7ariii purriflorn Lam. (63)
Occurrence of Spirobenzylisoquinolines by Plant Sources (1) Genm Corydalis C. ledebouriana K. et K .
C. lzrten (L.) DC.
Ledeborjdine (12) Ledeborine (19) (*)-Baddeanhe (14) Sibiricine (21) Ochrobirine (18)
IIAT-JUS
19601
P R E I S S E R E T AL. :
SPIROBESZTLISOQCISOLISE ALKALOIDS
C. ochotensis Turcz.
C. ociiofensis Tiircz. var. raddenna (Regel) S a k a i
C. orhroleuca Koch C . pacsoskii S . Busch C . srwerrowi Regel C. sibirica (L.) Pers. C . solida (L.) Swartz C. w g i n a n s Royle (2) G e w s Dzcentra D . c ~ ~ c ~ i l l a Bernh. rza (3) G e m s Fumaria F . zndzca (Haussk) Pugsley F . kralikzz Jord.
F. o 8 c i n a l i s L.
F . pariij’lora Lam.
F . roslellata Knaf.
F . schleicheri Soyer-Willem F . aaillantii Lois.
Ochotensimine (28) Ochotensine (27) ( * )-Tenhusomidine (24) Tenhusomine (17) Ochotensimine (28) Ochotensine (27) Raddeanamine (29) Raddeanidine (15) (+)-Raddeanine (13) Raddeanone (20) Ochrobirine (18) Corpaine (22) Corydaine (25) Severzinine (16) Ochotensine (27) Ochrobirine 118) Sibiricine (21) Ochotensimine (28) Ochotensine (27) Ochrobirine (18) (- )-Tenhusoniidine (23) Ochotensine (27) Fumariline (10) Fumaritine A\*-oside(2) Fumarofine 126) Parfumine (8) Fumaricine (3) Fumariline (10) Fumaritine (1) Fumaritrine ( 7 ) Fumarofine (26) Fumarophycine (4) 0-Methylfumarophycine (5) Parfumidine 19) Parfumidine (9) Parfurnine (8) Fumaritine 11) Parviflorine 130) Fumariline (10) Fumaritridine (6) Fumaritrine ( 7 ) Fumarofine (26) Parfumine (8) Fumaritine (1) Parfumidine (9) Parfumine ( 8 )
Botanical Distribution of Spirobenzylisoquinoline Alkaloids Corpaine 122): Corydaine (25): Fumaricine (3): Fumariline (10): Fumaritine (1) : Fumaritine .\’-oxide (2): Fumaritridine (6): Fumaritrine ( 7 ) : Fumarofine (26) : Fumarophycine (4): Ledeboridine (12):
315
C. paczoskii S . Busch C . paczoskii S . Busch F . opicinalis L. F . indica (Hausskj Pugsley F. opicinalis L . F. rostellata Knaf. F . schleicheri Soyer-Willem F . pariiflorii Lam. F . kralikii Jord. F . rostellata Knaf.
F . oficinalis L. F . rostellata Knaf. F . kralikii ,Jord. F . opicinalis L. F. rostellate Knaf. F. officinalis L. C. ledeboiiriana K . et K.
JOURSAL OF S.4TURAL
316
Ledeborine (19): 0-Melthylfumarophycine (5) : Ochotensimine (28): Ochotensine (2i):
Ochrobirine (18):
PRODUCTS
[VOL.
43,
NO.
3
C. ledebouriena K . et K.
F. oficinalis L.
C. ochotensis Turcz. C. ochotensis Turcz. var. raddeana (Regel) S a k a i C. solida (L.) SFartz C. ochotensis Turcz. C. ochotensis Turcz. var. raddeana (Regel) Nakai C. sibirica (L.) Pers. C. solida (L.) Swartz D. cuculleria Bernh. C. lutea (L.) DC. C. ochroleztce Koch C. sibirica (L.) Pers. C. caginens Royle
Parfumidine (9) : Parfumine (8):
Parviflorine (30) Raddeanamine (29) : Raddeanidine (15): (+)-Raddeanine (13) (*)-Raddeanine (14). Raddeanone (20): Serverzinine (16) : Sibiricine (21): (-)-Yenhusomidine (23) : (*)-Yenhusomidine (24): Yenhusomine (17):
F. oficinnlis L. F. pari’ijora Lam. F. eaillantii Lois. F. kralikii Jord. F . p a r x ’ j o r o Lam. F. rostellata Knaf. F. ~ a i l l ~ ~ Lois. itii F . pari’ijora. Lam. C. oc11otensi.s Turcz. var. C. ochotensis Turcz. var. C. ochotensis Turcz. var. C. Zedeboitriane K . et K. C. ochotensis Turcz. var. C. sewerzoii:i Regel C. ledeboziriana K . et K . C. sibirica (L.) Pers. C. esuginans Royle C. ochotensis Turcz. C. ochotensis Turcz.
raddeana (Regel) S a k a i raddeana (Regel) Kakai raddeana (Regel) Kakai raddeana (Regel) S a k a i
.ilphabetical List of Spirobenzylisoquinoline .4lkaloids Corpaine (22) Corydaine (25) Fumaricine (3) Fumariline (10) Fumaritine (1) Fumaritine X-oxide (2) Fumaritridine (6) Fumaritrine (7) Fumarofine (26) Fumarophycine (4)
Ledeboridine (12) Ledeborine (19) 0-Methylfumarophycine (5) Ochotensimine (28) Ochotensine (27) Ochrobirine (18) Parfumidine (9) Parfumine (8) Parviflorine (30) Raddeanamine (29)
Raddeanidine (15) (+)-Raddeanine (13) (*)-Raddeanine (14) Raddeanone (20) Severzinine (16) Sibiricine (21) (-)-Tenhusomidine (23) (*)-Yenhusomidine (24) Tenhusomine (17)
.4CKSOWLEDGllENT This compilation was carried out in conjunction with research supported by grant No. CA-11450 an-arded by the National Cancer Institute, DHEW. Recezaed 25 October 1979.
LITERATURE CITED . previous reviews on the spirobenzylisoquinoline alkaloids, see 1. FOI a. M. Shamma, in “The Alkaloids,’ R . H. F. Manske, ed., Vol. X I I I , p. 165, Academic Press, New York, 1971. b. RI. Shamma, “The Isoquinoline Alkaloids,” Academic Press, Ken- Tork, p. 381, 1972. C. 5. McLean and J. Whelan, in “ M T P I n t . Rev. of Sci., Alkaloids, Org. Chem., Series One,“ K . Wiesner, ed., J-01. 9, p. 161, Butterworths, London, 1973. d. 11,Shamma and J . L. Rloniot, “Isoquinoline Alkaloids Research, 1972-1977,” p. 325, Plenum Press, New Tork, 1978. e. D. B. RlacLean, I s r . J . Cheni., 16, 68 (1977). f . F. Santavj-, in “The Alkaloids,“ R. H. F. hlanske, ed., Yo]. XVII, p. 501, Academic Press, Ken- York, 1979.
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P R E I S S E R E T .4L.:
SPIROBE3ZTLISOQUISOLISE ALKALOIDS
317
2. R. H . F. Manske, Can. J . Res., 16B, 81 (1938). 3. a. Jl. Shamma, J. L. lloniot, R . H . F. llanske, W. Chan and K . Sakanishi, Chem. Cornmuz., 310 (1972). b. J. Imai, Y. Kondo and T. Takemoto, Heterocycles, 3, 467 (1975). 4. M.Jlathew and G. J. Palenik, A c t a Cryst., B31, 2899 (1975). 5. S.-M. Sasirov, I. A . Israilov, L. G . Kuzmina, bI. S. Yunusov, Tu. T. Struchkov and S. Tu. Tunusov, Khzm. Przrodn. Soedin., 752 (1978). 6 . a . B. C. Salliah, D. B. JIacLean, R . G. -1.Rodrigo and R . H . F. Manske, Can. J . Chenr., 55, 922 (1977). b. B. C. Salliah. D . B. MacLean. H . L. Holland and R . G. A. Rodrino, - . Can. J . Chew., S i , 1 2 5 (1979j. I . M. Shamma and C. D . Jones, J . A m . Chent. Soc., 92,4943 (1970). 8. T.-T. Wu, J. L. Moniot and 11.Shamma, Tetrehedron L e t t . , 3419 (1978). 9. a. B. C. Nalliah, R. H. F. Jlanske, R . G . A. Rodrigo and D . B. MacLean, Tetrahedron L e t t . , 2795 (1973). b. 31. Hanaoka and C. Mukai, Heterocycles, 6, 1981 (1977). 10. R . -4.Bell and J. K . Saunders, T o p i c s in Stereochem., 7, 1 (1973). 11. R . H. F. Manske, Can.J . Chem., 47, 1103 (19693. 12. T. F. Platonova, P . S. llassagetov, A. D. Kuzovkov and L. JI. Utkin, J . Gen. Chem. USSR,26, 181 (1956): Cheni. .1bstr., 50, 13950a-b (1956). 13. a. Spectrum S o . 947 in J. Holubek and 0. Strouf, "Spectral D a t a and Physical Constants of Alkaloids," Heyden &- Son Ltd., London. b. Spectrum S o . 945, ibid. c. Spectrum S o . 946, ibid. d. Spectrum S o . 199, ibid. 14. H. G. Kir-akov, D . W.Hughes, B. C. Salliah and D . B. AIacLean, Can. J . Chem., 57, 53 (1979). 15. T. Kishimoto and S . Vj-eo, J . C h e w . Soc., C , 1644 (1971). 16. D. B. hlaclean, R.A . Bell, J. K. Sannders, C.-T. Chen and R . H . F. Mansake, C a n . J . Chem., 1 7 , 3593 (1969). 17. I. A. Israilov, 31.S. Tunusov and S.1-u.Tunusov, Khini. Prirodn. Soedin., 11, 284 (1975). 18. C. K. l u and D. B. MacLean, Cun. J . Cheni., 49, 3025 (1971). 19. B h . Kiryakov and P. P. Panov, C. R.d c n d . Birig. S e i . , 29, 677 (1976); Cheni. Absir., 85, 119633 il976j. 20. R. H . F. Manske, Gzn. J . Res., 16B, 438 (1938). 21. J. K. Saunders, R.;i.Bell, C.-T. Chen, D . B. 1IacLean and R . H . F. blanske, Can.J . Cheni., 16, 2873 (1968). 22. T. Kishimoto and S. Uj-eo, J . Chevi. Soc., C! 2600 (1969). 23. Kh. Ph. Baisheva, D. .1.Fesenko, B. K. Rostotskii and 11. E. Perelson, Khini. Prirodn. Snediw., 6 , 456 (1970). 24. S . 11.hlollov, G . I . l a k i m o v and P. P. Panov, C. R.A c a d . Bztlg. Sei., 20, 557 (1967). 25 51. Castillo, J . K. Eaunders, D . B. NacLean, S . AI. ?rIollov and G. I . Takimov, Can. J . Chem., 49, 139 (1971). 26. T. Kametani, 31.Takemura, 31. Ihara and E;.Fukumoto, Heterocycles, 4, 723 11976). 27. K.11. Mollov and G . I . Takimov, C. R . d c a d . Bitlg. Sei., 21, 1325 (1971). 28. Y . 11.1Iollov, H . G . Kirjakov and G . I . Takimov, PhyfocheviisfrJ, 11, 2331 (1972). 29. Kh. G . Kiryakov and P. P. Panov, C. R..lend. Biilg. Sci., 25, 345 (1972). 30. '1.Israilov, AI. S.Tunusov and 8 . 1-u. 1-unusov, Dokl. Akad. .I-oiik SSSR,189, 1262 (Eng. 9993 (1969). 30a. An nmr spectrum of 8 in CDC1, at 200 hIHz ( F T ) showed 6 2.37 s (3H), 3.85 s (3H), 6.16 s @HI,6.30 s ( l H ) ,6.58 s ( l H ) ,6.89 d i l H ) and 7.10 d (1H):S. F. Hussain and 11. Shamma, unputilished results. 31. K h . G . Biryakov and P . P . Panov, Folio M e d i c a , 16, 101 (1974'). 32. I . -4.Israilov, 11. 9. l u n u s o v and S. T.Tunusov, Khim.P r i r o d n . Soedin.,6 , 518 (1970). 32a. -innrnr spectrum of 9 in CDC13 at 200 1IHz ( F T ) showed 6 2.35 s (3H1, 3.59 s (3H), 3.84 s (3H), 6.17 s i l H ) , 6.18 s (2H), 6.60 s ( l H ) , 6.92 d (1H) and 7.12 d ilH): S. F. Hussain and 11.Gliamma, unpublished result 33. I-.B. Pandey, B. Dasgupta and . Ghosal, J . Inst. Cheni. Cuiczrtia, 46, 120 (1974). 34. T-. B. Pandey, -1.B. Ray and B. Dasgupta, Phyiocheniisfry, 18, 695 (1979). 35. I . -1.Israilov, 11.S. Ynnusov and P. 1-u. Tunusov, K h i n i . P r i r o d n . Soedin., 3, 366 (1977). 36. N.31.31ollov and G . I . Takimov! C. R . rlcad. Bulg. Sei.: 25, 59 (1972). 37. T. Kametani, AI. Takeniura, 11. Ihara and K. Fukumoto, J . Chem. Soc., P e r k i n I , 390
-
I
I.
---
j l Y l l I.
38. T . Irgashev, I . A . Israilov, 11. S. Tunusov and E. T u . Tunusov, K h i m . P r i r o d . Soedzn., 536 (1978): J . -Yoitrral C o m p o u n d s , 464 (1979). 39. S.-T. Lu, T.-L. du, T. Kametani and 51. Ihara, Heterocjcles, 3, 301 (1975). 40. S.-T. Lu. T.-L. Su.T. Kametani, A . Uiiie, 11. Ihara and K . Fukumoto, J . C h e m . Soc., Perkin I,' 63 (1976):
318
JOURSAL O F NATURAL PRODUCTS
[VOL.
43,
60.3
41. D. W.Hughes, B. C. Kalliah, H . L. Holland and D. B. hlacLean, Can. J . Chem., 55, 3304 (1977). 42. R . H. F. Manske, Can. J . Res., 17B, 89 (1939). 43. R. H. F. Manske, Can. J . Res., 17B, 95 (1939). 44. K . S . hlargvelashvili, 0. E. Lasskaya, A. T. Kiryanova and 0. Ii.Tolkachev, Khim. Przrodn. Soedin., 848 (1974). 45. R . H . F. Manske, R . G. A . Rodrigo, D. B. hlaclean, D. E. F. Gracey and J. K. Saunders, Can. J . Chem., 47, 3589 (19F9). 46. Ref. (3a) and unpublished results. 47. R . H. F. Manske, Can. J . Res., 14B, 354 (1936). 48. R . H. F. hlanske, R . G. A. Rodrigo, D. B. MacLean, D. E. F. Gracey and J. K . Saunders, Can. J . Chem., 47, 3585 (1969). 19. C. K . Yu, J . K. Saunders, D . B. hlacLean and R. H. F. hlanske, Cali. J . Chem., 49, 3020 (1971). 50. Kh. Sh. Baisheva, D. A . Fesenko, B. K . Rostotskii and hl. E. Perelson, Khim. Prirodn. Soedin., 6, 574 (1970). 51. 3'. N . Margvelashvili, 0. E. Lasskaya, -4.T. Kiryanova and 0. h-. Talkachev, Khim. Prirodn. Soedzn., 1, 118 (1976). 52. H . L . Holland, M. Castillo, D . B. hlacLean and I. D. Spenser, Can. J . Chem., 52, 2818 (lS74\ -,. 53. R. H . F. hlanske, Can. J . Res., 18B, 75 (1940). 54. S. hlacLean, 11.43.Lin and R . H . F. Manske, Can. J . Chem., 44,2449 (1966). 55. R . B. Kelly and B. A. Beckett, Can. J . Chem., 4 i , 2501 (1969). 56. S. h l c l e a n , M . 4 . Lin, -4.C . MacDonald and J. Trotter, Tetrehedron Lett., 185 (1966). 5 7 . A. C. ;\lacDonald and J. Trotter, J . Chem. Soc., B , 929 (1966). 58. C. K. Y u , H. L. Holland, D. B. MacLean, R.H. F. Manske and R. G. A. Rodrigo, unpublished observations (1972): see ref. (52). 59. S. hIcLean, 11.4.Lin and J. Whelan, Can. J . Chem., 48, 948 (1970). G!l . H . Irie, T. Kishimoto and S. Uyeo, J . Chem. Soc., C, 3051 (1968). 61. S. McLean and M.-S. Lin, Tetrahedron Lett., 3819 (1964). 62. Kh. G. Kiryakov and P. P. Panov, C. R . A c a d . Bulg. Sci., 24, 1191 (1971). 63. S. F. Hussain and 11.Shamma, Tetrahedron Letf., in press. \--
