Synthesis of docetaxel and butitaxel analogues through kinetic resolution of racemic beta-lactams with 7-O-triethylsilylbaccatin III

J Org Chem. 2007 Feb 2;72(3):756-9. doi: 10.1021/jo061339s.

Abstract

The kinetic resolution of racemic cis-4-phenyl- and cis-4-tert-butyl-3-hydroxy-beta-lactam derivatives with 7-O-triethylsilylbaccatin III yielded paclitaxel and butitaxel analogues with high diastereoselectivity. The results demonstrated that the tert-butyldimethylsilyl protecting group at the C3-hydroxy group of the beta-lactams provided optimum kinetic resolution in comparison with the sterically less demanding triethylsilyl group and the larger triisopropylsilyl group. In addition, it was found that the C4 beta-lactam substituents also influenced diastereoselectivity. The C4 tert-butyl-beta-lactams provided better diastereoselectivity than the corresponding C4 phenyl beta-lactams.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alkaloids / chemistry*
  • Antineoplastic Agents / chemical synthesis*
  • Docetaxel
  • Kinetics
  • Models, Chemical
  • Stereoisomerism
  • Taxoids / chemical synthesis*
  • Taxoids / chemistry*
  • beta-Lactams / chemistry*

Substances

  • Alkaloids
  • Antineoplastic Agents
  • Taxoids
  • beta-Lactams
  • butitaxel
  • Docetaxel
  • baccatin III