PROCESS FOR THE SYNTHESIS OF VINBLASTINE AND VINCRISTINE AND RELATED DIMER ALKALOID COMPOUNDS

摘要

A process for the synthesis of bisindole alkaloidsof the vinblastine and vincristine family from an indole unit,such as catharanthine, and a dihydroindole unit, such asvindoline, wherein conversion of an initially-formed dimericiminium intermediate to an enamine is achieved by a novel1,4-reduction method employing various 1,4-dihydropyridinecompounds. The resulting enamine can be transformed to asecond iminium intermediate by controlled aeration and oxidationin the presence of various oxidizing reagents. The secondiminium intermediate is then reduced with alkali metal boro-hydride to produce the target compound vinblastine or vincristine.The entire process can be conducted in a one-pot operation toobtain the target product without isolation of the intermediates.