A short enantioselective pathway for the synthesis of the anti-influenza neuramidase inhibitor oseltamivir from 1,3-butadiene and acrylic acid

J Am Chem Soc. 2006 May 17;128(19):6310-1. doi: 10.1021/ja0616433.

Abstract

A short synthetic pathway has been developed for the synthesis of oseltamivir (1) or the enantiomer (ent-1). The intermediates and conditions for this process are summarized in Scheme 1. The synthesis provides a number of advantages: (1) use of inexpensive and abundant starting materials; (2) complete enantio-, regio-, and diastereocontrol; (3) avoidance of explosive, azide-type intermediates; (4) good overall yield (ca. 30%, still not completely optimized); and (5) scalability.

MeSH terms

  • Acrylates / chemistry
  • Antiviral Agents / chemical synthesis
  • Butadienes / chemistry
  • Humans
  • Influenza, Human / drug therapy*
  • Neuraminidase / antagonists & inhibitors*
  • Oseltamivir / chemical synthesis*
  • Stereoisomerism

Substances

  • Acrylates
  • Antiviral Agents
  • Butadienes
  • Oseltamivir
  • Neuraminidase
  • acrylic acid
  • 1,3-butadiene