Application of vicarious nucleophilic substitution to the total synthesis of dl-physostigmine

J Org Chem. 2003 Aug 8;68(16):6133-9. doi: 10.1021/jo026438u.

Abstract

A concise, highly efficient formal total synthesis of dl-physostigmine is described, using a relatively simple method that should be adaptable to the synthesis of homologous members of this type of alkaloid. The key step in the synthesis is a new vicarious nucleophilic substitution reaction between p-nitroanisole and a C-silylated derivative of N-methylpyrrolidinone. Subsequent conversion of the initial adduct to the tricyclic framework of physostigmine follows a well-established protocol and provides the key intermediate 8 in high yield. The vicarious nucleophilic substitution reaction has also been extended to six-membered lactams, with encouraging results.

MeSH terms

  • Bromine / chemistry
  • Catalysis
  • Cholinesterase Inhibitors / chemical synthesis*
  • Crystallography, X-Ray
  • Fabaceae / chemistry
  • Gas Chromatography-Mass Spectrometry
  • Indicators and Reagents
  • Magnetic Resonance Spectroscopy
  • Physostigmine / chemical synthesis*
  • Stereoisomerism
  • Streptomyces / metabolism

Substances

  • Cholinesterase Inhibitors
  • Indicators and Reagents
  • Physostigmine
  • Bromine