Eburnamine

In the eburnamine-vincamine sub-group, Takano etal. have given details99" of their synthesis of ( )-eburnamine.99i Other synthetic work reported includes further preparations of ( )-vincamone (eburnamonine)100" and ethyl apovin-caminate,100 and a modification of Szantay s route to vincamine which was intended to result in an asymmetric synthesis of vincamine-5-carboxylic acid, since L-tryptophan was used as starting material. Unfortunately, racemization of C-5 occurred during the synthesis, so the final product was an ester of ( )-vincamine-5-carboxylic acid.101... 

Intramolecular nucleophilic substitution of a chlorine atom in an a-chloro amide, by a ketone enolate, causes cyclization and this has been used in the synthesis of some alkaloid ring systems (equation 87)576. The product of this reaction is a key intermediate for the synthesis of Strychnos, Aspidosperma, Schizozygane and Eburnamine alkaloids. 

Aspidospermine-Aspidofractine-Eburnamine Group. The structural and biosynthetic relationships between the various alkaloids in this group, which are referred to by the authors as the plumerane alkaloids, since they occur exclusively in plants of the subfamily Plumerioidae of the Apocynaceae, have been discussed in some detail.1110... 

Pleiocarpine and eburnamine are among the alkaloids of Hunteria elliotti the former occurs in the seeds and the latter in the stem-bark and leaves.59" A base, described as 14,15-didehydro-3-oxokopsinine N-oxide, has been isolated68" from Vinca erecta, but the evidence on which this structure is based is lacking. 

Recent extractions440 of the leaves of Cinchona ledgeriana have resulted in the isolation of quinamine (previously observed), 3-ep/-quinamine, aricine, and a new alkaloid which may prove to be stereoisomeric with quinamine. 11-Hydroxy-pleiocarpamine occurs in Vinca erecta 4b and herbacine and herbaine in V. herbacea.44c Yohimbine appears to be the major alkaloid of the trunk bark of Pausinystalia macroceras, in which it occurs with four other alkaloids of this group.44d Pleiocarpamine occurs in association with nine alkaloids of the aspidospermine-eburnamine group in the stem and root bark of Hunteria elliottii (Stapf.) Pichon.44e... 

Among the alkaloids of Hunteria ebumea Pichon (Table I) were four interrelated ones (11). Two of them, eburnamine and isoeburnamine, were diastereoisomeric pentacyclic indoles (XVII) convertible by acids into eburnamenine, an A-vinylindole (XVIII), on the one hand, and by chromic acid into eburnamonine, an V-acylindole (XIX), on the other. Reduction of eburnamonine with lithium aluminum hydride regenerated the alcohols, XVII (7,11). When eburnamonine was heated with selenium... 

These results by themselves did not unequivocally establish the structure of eburnamonine (XIX) this was secured not only by a degradation of eburnamine (see Section II, B) in which the uncertain features (ring D and the ethyl group) were not affected but also by a total synthesis of the alkaloid (Chart I). Condensation of jS-ethyl-jS-formyladipic acid with tryptamine gave in one step di-eburnamonine lactam (XXVI) which,... 

In view of the foregoing described acid-catalyzed transformations and the fact that inorganic acids were used in the isolation of the alkaloids from the plant material, it is quite possible that the ratios of isoeburn-amine to eburnamine and ebumamenine were quite different originally, even to the extent of the exclusion of the last two. 

By the use of mass spectroscopy coupled with deuterium labeling, eburnamonine, (iso (eburnamine, and ebumamenine have been shown to exist (stereochemistry not specified) in Rhazya stricta Decaisine, and ebumamenine itself in Aspidosperma quebracho bianco Schlecht (19). The obtention of ebumamenine from Pleiocarpa species is described in Section III. 

Under this heading is discussed the chemistry of those alkaloids, isolated from Vinca species (principally V. minor), that are closely related to eburnamine and its congeners. A table of Vinca alkaloids is given elsewhere (see Chapter 12). 

The hydroxyl group in XXXV could not be acetylated instead, the iV-vinyl indole, the apo compound, XXXVIII was obtained. In fact, simple heating or solution of the alkaloid in strong acid was all that was necessary. The latter experiment, which finds an analogy in eburnamine itself, required the intermediacy of the iminium form (see Chart II). This iminium form was apparently stable in strong acid, since vincamine in 11 N hydrochloric acid had a UV-spectrum with a long wavelength maximum at 360 mp (log e = 3.85) compatible with XXXIX which reverted irreversibly into apovincamine (XXXVIII R = H) upon dilution (18). 

The only tertiary base aside from the eburnamine group whose structure has been established is burnamicine (XLVII see Table I). It is a 2-acylindole, which in acidic solution existed as an indole. Its formula... 

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