Stereoselective synthesis of (-)-cephalotaxine and C-7 alkylated analogues

J Org Chem. 2004 Apr 30;69(9):3087-92. doi: 10.1021/jo049884l.

Abstract

A total asymmetric synthesis of (-)-cephalotaxine is reported. The chemistry of alpha,beta-unsaturated gamma-lactams was used to access the 1-azaspiro[4.4]nonane skeleton in enantiomerically pure form via a stereocontrolled semipinacolic rearrangement of an alpha-hydroxyiminium ion. This spiro compound was transformed into (-)-cephalotaxine without any racemization or epimerization by following the racemic synthesis reported by Kuehne. We thus performed a total synthesis of (-)-cephalotaxine in 98.7% ee with an overall yield of 9.8% over a 16 steps sequence. This synthetic process was adaptable to the access of some alkylated analogues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation
  • Aza Compounds / chemistry
  • Harringtonines / chemical synthesis*
  • Homoharringtonine
  • Imines / chemistry
  • Lactams / chemistry
  • Molecular Structure
  • Spiro Compounds / chemistry
  • Stereoisomerism

Substances

  • Aza Compounds
  • Harringtonines
  • Imines
  • Lactams
  • Spiro Compounds
  • Homoharringtonine