Eburnamine alkaloids

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. 

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 structures of haplophytine and cimicidine are still obscure in a recent investigation of the constituents of H. cimicidum, five additional bases were isolated, but no further data concerning haplophytine and cimicidine were reported (5). The additional bases include the two epimers eburnamine (II R = a-OH) and isoeburnamine (II R = jS-OH), which are characteristic alkaloids of Hunteria eburnea Pichon, and O-methyleburnamine (II R = a-OMe). The constitution of this last base was established by its conversion by boiling alcoholic picric acid into the picrate of eburnamenine (HI), and by its oxidation with chromic oxide in pyridine to the lactam eburnamonine (II R = =0). Two new bases were also isolated, namely, haplocine and haplocidine. 

Haplophyton cimicidum thus joins the interesting group of plants which produce both the aspidospermine and the biogenetically intimately related eburnamine types of alkaloids. 

The knowledge of the key fragmentation routes of eburnamine and some related alkaloids confirmed or elucidated the structures of the alkaloids 11-methoxy-vincamine,100 vincaminine,102 and vinci-nine,102 of the same skeletal type as eburnamine. Alkaloids of the mavacurine-pleiocarpamine group (212)103 are characterized by a key fragment corresponding to the loss of the ester group and... 

Aspidospermine-Aspidofractine-Eburnamine Group. The leaves of Pandaca minutiftora contain (+)-vincadifformine, which also occurs in the leaves of Amsonia tabernaemontana, together with ten other alkaloids [tabersonine, (+)-l,2-dehydroaspidospermidine, (—)-quebrachamine, lochnericine, ( ) and (—)-vincadine, (-)and ( )-epivincadine, (+)-14,15-dehydrovincadine, and (+)-14,15-dehydroepivincadine] the roots contain the first four alkaloids and ebumamonine. 

A new line to the synthesis of the eburnamine type alkaloids has produced (Scheme 17) ( + )-vincamine (105a), ( )-eburnamine (105b), and ( + )-eburnamonine " (105c). Acid-catalysed rearrangement of the carbinolamide (107) gave homoeburnamenine (106) which contained all the carbons necessary for the formation of vincamine. 

Other ions arise due to loss of fragments from the molecular ion of the dimeric alkaloid. If the pleiocarpinine component is involved then, amongst others, the ion X m/e 506) is formed if the eburnamine part is involved peaks due to the ions y m/e 560) and z m/e 601) are observed. In addition, peaks at m/e 365 aa) and... 

Eburnamine-Vincamine Alkaloids.—So far most of the effort on indole alkaloid biosynthesis has been concentrated on the Corynanthe, Aspidosperma, and Iboga systems. It is welcome, therefore, to see the preliminary results of an investigation of the biosynthesis of vincamine (10).6 Comparable incorporations were observed for [ar-3H]tryptophan, [ar-3H]stemmadenine (5), and [ar-3H]taber-sonine (9). These results support the proposal7 that vincamine is a transformation... 

Hunteria zeylanica has afforded several alkaloids of the eburnamine group (79). These included four previously known alkaloids, ebur-namine (113), isoeburnamine (114), O-methylebumamine (115), and... 

---