A HIGHLY EFFICIENT AND COMMERCIALLY IMPORTANT SYNTHESIS OF THE ANTITUMOR CATHARANTHUS ALKALOIDS VINBLASTINE AND LEUROSIDINE FROM CATHARANTHINE AND VINDOLINE

Extensive studies of various reaction parameters for the chemical coupling of catharanthine (1) and vindoline (2) followed by evaluation of highly unstable intermediate by careful reaction control have provided essentially a quantitative yield in this coupling reaction. Subsequent regioselective red...

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Published inHeterocycles Vol. 27; no. 8; pp. 1845 - 1853
Main Authors KUTNEY, JP, CHOI, LSL, NAKANO, J, TSUKAMOTO, H, MCHUGH, M, BOULET, CA
Format Journal Article
LanguageEnglish
Published Tokyo Japan Inst Heterocyclic Chemistry 01.08.1988
Subjects
Chemistry
Chemistry, Organic
Physical Sciences
Science & Technology
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Summary:Extensive studies of various reaction parameters for the chemical coupling of catharanthine (1) and vindoline (2) followed by evaluation of highly unstable intermediate by careful reaction control have provided essentially a quantitative yield in this coupling reaction. Subsequent regioselective reduction of the resultant intermediate 3 by select NADH models affords a high yield of an enamine (5) which, without isolation, is selectively oxidized to unstable iminium intermediates 6 and 7 and the latter, again without isolation, are finally reduced to vinblastine (8,40%), leurosidine (10, 16%), and 3'', 4,-anhydrovinblastine (4, 12%). The entire process of five steps (1 .fwdarw. 11 + 2 .fwdarw. 3 .fwdarw. 5 .fwdarw. 6,7 .fwdarw. 8,10,4) can be achieved in a one-pot operation and the high overall yield of vinblastine (8) requires that each reaction must proceed in yields in excess of 80%.
ISSN:0385-5414
1881-0942
DOI:10.3987/com-88-4611