Cocculus erythrina alkaloid

Erythrina Alkaloids.—AT-Norprotosinomenine (74) is known to be a key precursor for Erythrina alkaloids (cf. Vol. 8, p. 10 Vol. 9, p. 16 ref. 2), and its unique role compared to isomeric isoquinolines has been confirmed for coccuvine (80) in Cocculus laurifolius.22 The incorporation of JV-norprotosinomenine (74) [the (+)-(S)-isomer is preferred] was with loss of the O-methyl group at C-7 and complete retention of the 4 -0-methyl group, measured relative to a secure internal tritium marker. The results for coccuvine (80) show that no symmetrical intermediate is involved, unlike, e.g., for erythraline. Consequently the same biosynthetic route is not followed. Plausibly this route could be (74) —> (75) — (76) - (77) (Scheme 7). The unsymmetrical intermediate... 

A new abnormal Erythrina alkaloid, obtained from the leaves of Cocculus laurifolius, was assigned the structure isococculine (7) on the basis of spectral and chemical studies.7... 

In the intervening 13 years the subject has expanded dramatically over 60 compounds are now classified as Erythrina alkaloids, and the structures of most of these have been deduced from a combination of mass spectral fragmentation analysis, H-NMR spectral interpretations, and chemical correlations with alkaloids of known structures. Some unusual alkaloids have been obtained from certain Cocculus species and a new, as yet small, subgroup, the Homoerythrina alkaloids, has been recognized. The biosynthetic pathway from tyrosine through the aromatic bases to the ery-throidines has been elucidated, and some significant advances have been made in methods of total synthesis. Reviews of the Erythrina alkaloids since 1966 have appeared (3-6). 

There are now over 60 Erythrina alkaloids of known structure 1-61 (see Figs. 2-4) and several more, the structures of which are yet to be assigned (12). The alkaloids occur in species of Erythrina (Leguminosae), a genus of wide distribution in tropical parts of the world, and in species of Cocculus... 

Only two normal Erythrina alkaloids have been isolated from Cocculus species, dihydroerysodine (47) (75) and dihydroerysovine (44), the latter recently from C. trilobus (57). Neither alkaloid has been found in Erythrina species. The structure 44 for dihydroerysovine was deduced from the spectroscopic evidence and by methylation using diazomethane to give the known dihydroerysotrine (38). The positions of the aromatic substituents were determined by detailed NMR experiments using NOE and INDOR techniques (see Section II,C,2d). 

Cocculolidine, an alkaloid with striking insecticidal properties isolated from the leaves of Cocculus trilohus DC, has recently been isolated and assigned the structure (XCIV) of a lower homolog of -erythroidine 50). The degradation reactions reported closely parallel those of /3-erythroidine. This makes the second report of Erythrina alkaloids in Cocculus species, dihydroerysodine having been isolated earlier from C. laurifolius 51). 

A new erythrina alkaloid, erythroculine, from Cocculus laurifolius has been shown to have the structure (167). The ester group may be reduced with lithium aluminium hydride and the acetyl ester of the resulting alcohol on treatment with cyanogen bromide affords the hindered diphenyl (168), with loss of hydrogen bromide and methanol. This on reduction to the secondary base, N-methylation, and successive Hofmann degradations affords an olefin that may be oxidised to the tricarboxylic acid (169).The base represents a novel structure in having the additional carbon atom linked to the ring system. 

Erythrina alkaloids, which are known to arise biogenetically from benzyl-tetrahydroisoquinolines, are found to occur in numerous Erythrina species of the family Fabaceae (Leguminosae), the only exception being their presence in the genus Cocculus (Menispermaceae) (55). Erythrina alkaloids are of wide interest because of their remarkable physiological action. 

Many Erythrina alkaloids possess curare-like action and interact with acetylcholine receptors. Extracts of many Erythrina species are used in indigenous medicine, particularly in India. Cocculine and cocculidine nitrates have been reported to show hypotensive action in dogs (Dyke and Quessy, 1981). The insecticidal alkaloid cocculolidine (109) has been isolated from Cocculus trilobus and C. carolinus... 

It is of chemotaxonomic interest that the bases cocculine and cocculidine, which closely resemble some of the Erythrina alkaloids, have been isolated from Cocculus species (Menispermaceae). The recent isolation from C. trilobus of coccutrine, an apparent relative of protostephanine, as reflected by the ring-A oxygenation pattern, suggests that the dibenzazonines are not an end point in alkaloid biosynthesis. 

It is interesting to note that a member of the Erythrina alkaloids, dihydroery-sodine, was isolated (0.003%) from a Menispermaceae, Cocculus laurifolius (158). 

The isolation of these new 8-oxo-alkaloids adds two further examples to a growing family of 8-oxo-erythrina alkaloids, other examples being erythrabine (Id) and erysotramidine (If) (Ito et al. 1973) isolated from E.arborescens and crystamidine (In) from E.crysta-galli (Ito et al. 1973) whilst two other oxo-alkaloids have been found in Cocculus laurifolius (Uprety and Bhakuni 1975), (Bhakuni and Jain 1980). 

Only 3 of the 12 species of Cocculus (Menispermaceae) have been examined for alkaloids and most studies have concerned C. laurifolius, which has yielded the greatest number of alkaloids (see Table I) (57, 55-58, 60, 69-76). The Erythrina-type alkaloids obtained from Cocculus are abnormal in the sense that they contain no oxygen function at C-16, the only exceptions being dihydroerysovine (44), dihydroerysodine (47), and erythroculine (53). Erythroculine is, however, unusual in that it has a methoxycarbonyl group at C-16. The two alkaloids isococculidine (36) and isococculine (37) are of theA2(l)-alkene type rather than the Al(6)-alkene type. 

This report embodies the work published on the isolation, structure determination, and synthesis of Erythrina, Cocculus, Cephalotaxus, and other related alkaloids. 

Erythrina (Fabaceae) and in Cocculus (Menispermaceae) (Fig. 32.34). Alkaloids of this type have been reported from a Dysoxylum species (Meliaceae), but some question about the identify of the plant material exists (Waterman, 1993). Seeds of Erythrina species typically contain about 0.1% of the alkaloids, but these compounds are also known from the leaves, stalks, stems, bark, roots, pods, and flowers (Dyke and Quessy, 1981). 

---