Stereocontrolled total synthesis of (+)-vinblastine

Abstract

Abstract Stereocontrolled total synthesis of (+)-vinblastine ( 1 ) has been achieved using a novel radical-mediated indole synthesis developed in our laboratories. The isothiocyanate 18 , prepared readily from quinoline 17 , underwent a facile addition of the malonate anion to give 19 . The o -alkenylthioanilide 19 was then converted to indole 20 by radical cyclization and protection. (−)-Vindoline ( 2 ) was prepared from this key intermediate 20 in a highly efficient manner. The indole core of the 11-membered intermediate 3 was constructed similarly from quinoline. The critical coupling reaction between 2 and the chloroindolenine derived from 3 proceeded with complete control of stereochemistry to give the desired product 66 in 97 % yield, which could be successfully converted to (+)-vinblastine ( 1 ).