Stereocontrolled total synthesis of (+)-vinblastine

Stereocontrolled total synthesis of (+)-vinblastine ( ) has been achieved using a novel radical-mediated indole synthesis developed in our laboratories. The isothiocyanate , prepared readily from quinoline , underwent a facile addition of the malonate anion to give . The -alkenylthioanilide was then...

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Bibliographic Details
Published in:Pure and applied chemistry 2003-01, Vol.75 (1), p.29-38
Main Authors: Yokoshima, Satoshi, Ueda, T., Kobayashi, S., Sato, A., Kuboyama, Takeshi, Tokuyama, H., Fukuyama, T.
Format: Article
Language:English
Subjects:
Quinoline
Stereochemistry
Synthesis
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Summary:Stereocontrolled total synthesis of (+)-vinblastine ( ) has been achieved using a novel radical-mediated indole synthesis developed in our laboratories. The isothiocyanate , prepared readily from quinoline , underwent a facile addition of the malonate anion to give . The -alkenylthioanilide was then converted to indole by radical cyclization and protection. (−)-Vindoline ( ) was prepared from this key intermediate in a highly efficient manner. The indole core of the 11-membered intermediate was constructed similarly from quinoline. The critical coupling reaction between 2 and the chloroindolenine derived from proceeded with complete control of stereochemistry to give the desired product in 97 % yield, which could be successfully converted to (+)-vinblastine ( ).
ISSN:0033-4545
1365-3075
DOI:10.1351/pac200375010029