A NEW METHOD FOR SYNTHESIS OF COMPOUNDS IN THE VINBLASTINE-VINCRISTINE SERIES

摘要

A concerted process for the synthesis of a dimer consisting of an indole unit and a dihydroindole unit possessing natural stereochemistry which comprises: (a) forming an N-oxide intermediate from said indole unit; (b) treating said N-oxide indole intermediate in the presence of acetic anhydride or halogenated derivative thereof to effect a Polonovski-type fragmentation reaction; (c) without isolating the N-oxide indole intermediate and at a temperature of about -10 DEG C. to +10 DEG C., coupling said reaction product with a dihydroindole unit in the presence of acetic anhydride or a halogenated derivative thereof at a low temperature of about -10 DEG C. to +10 DEG C. under inert conditions; and (d) subsequently reducing the immonium nitrogen on the indole unit by reacting with aqueous alkali metal borohydride to produce a dimer.