60395-02-0Relevant articles and documents
A HIGHLY EFFICIENT AND COMMERCIALLY IMPORTANT SYNTHESIS OF THE ANTITUMOR CATHARANTHUS ALKALOIDS VINBLASTINE AND LEUROSIDINE FROM CATHARANTHINE AND VINDOLINE
Kutney, James Peter,Choi, Lewis Siu Leung,Nakano, Jun,Tsukamoto, Hiroki,McHugh, Michael,Boulet, Camille Andre
, p. 1845 - 1854 (2007/10/02)
Extensive studies of various reaction parameters for the chemical coupling of catharanthine (1) and vindoline (2) followed by evaluation of highly unstable intermediates 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, 40percent), leurosidine (10, 16percent), and 3',4'-anhydrovinblastine (4, 12percent).The entire process of five steps (1->11+2->3->5->6,7->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 80percent.
