Stereocontrolled total synthesis of (+)-vinblastine
S. Yokoshima, T. Ueda, S. Kobayashi, A. Sato, T. Kuboyama, H. Tokuyama,
and T. Fukuyama+
Graduate School of Pharmaceutical Sciences, The University
of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
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).
*Lecture presented at the 14th International Conference
on Organic Synthesis (ICOS-14), Christchurch, New Zealand, 14-18 July
2002. Other presentations are published in this issue,
pp. 1-70.
Page last modified 27 February 2003.
Copyright © 2003 International Union of Pure and Applied Chemistry.
Questions or comments about IUPAC, please contact, the Secretariat.
Questions regarding the website, please contact web
manager.
