Synthesis of vinblastine, vincristine and vinrosidine - by converting catharanthine to its (N)-oxide deriv. followed by treatment with vindoline

摘要

Synthesis of vinblastine, vinctistrine and vinrosidine comprises either (a) (i) hydrogenation and acetylation of catharanthine to 20- or 15-acetocydihydrocatharanthine (ii) converting 20- or 15-acetoxydihydrocatharanthine into the corresp. N-oxide, (III) treating the N-oxide with vindoline (CCl3CO)2 to give the corresp. binary quat. salt (iv) converting the binary quat. salt to vinblastine or vinrosidine by redn. and alkaline hydrolysis and opt. (iv) oxidising vinblastine to vincristine. or (b) (i) converting catharanthine to 20- or 15 hydroxydihydrocatharanthine (ii) converting to the corresp. N-oxide and (iii) treating the N-oxide with vindoline to give vinblastine or vinrosidine respectively and opt. (by) oxidising vinblastine to vinrosidine. Vinblastine, vincristine and vinrosidine are anticancer agents. Vinblastine is used for treatment of Hodgkins' disease and chonocarcinomas and vincristine is used for treatment of acute leukaemia in children.