Eburnamine- Vincamine Alkaloids

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 

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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. 

Tkylor W I 1965 The Pentaceras and the eburnamine (Hunteria)-vincamine alkaloids. In Manske R H F (ed) The alkaloids. VIII. Academic Press New York, 249-267... 

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 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... 

Almost all the alkaloids isolated from V. minor are derived from the type III moiety 41) belonging to the vincamine, Aspidosperma, and quebrachamine subclasses. In this sense there is more uniformity among the alkaloids of V. minor than the other Vinca species. The alkaloids are also unusual in that amongst the three subclasses are found racemic alkaloids, namely, d(-eburnamine (vincanorine), dZ-A-methylquebrach-amine d -vincadifformine and its dZ-l-methyl derivative (minovine) (see Table II). 

The absolute configuration of vincamine and hence the other eburn-amine alkaloids has been accomplished by showing that the optical rotatory dispersion curve of ( —)-l,l-diethyl-l,2,3,4,6,7,12,12b-octa-hydroindolo[2,3a]quinolizine (XVI) (mp 105°-106°) obtained by a Wolf-Kishner reaction on (— )-eburnamonine was enantiomeric with (-I-)-l,2,3,4-tetrahydroharman (XVII) (24). The i -configuration has to be ascribed to the latter compound because it has been converted into V-carboxyethyl-D-alanine (XVIII) of known absolute configuration (24). This work, with the exception of the Schizozygia alkaloids, establishes the absolute configurations of the eburnamine alkaloids since they have all been interrelated. 

Kopsia officinalis, endemic to the Yunnan province of China, gave the bisin-dole alkaloid, ( + )-kopsoffine (613) (377). As in the case of norpleiomutine (606), the mass spectral fragmentation was similar to that of (—)-pleiomutine (607), except that the of 613 (m/z 616) is 14 mass units less than that of 607. The H NMR spectrum confirmed the absence of NMe in the kopsinine half, while the H(16) coupling constants of 11 and 5 Hz indicated that H(16 ) is axial or P, and that the C(16 ) substitution is a. Comparison of the C NMR spectral data with those of (—)-kopsinine (608) and (+ )-vincamine provided further support for the proposed structure in which the eburnane half is the optical antipode of the corresponding half in (—)-norpleiomutine (606). Confirmation of this was provided by semisynthesis, from the condensation of ( + )-eburnamine (614) (from LiAlH4 reduction of (—)-eburnamonine 615) with (—)-kopsinine (608) under acidic conditions, which led to a product identical with (+ )-kopsoffine. 

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