Total synthesis of A-315675: a potent inhibitor of influenza neuraminidase

J Am Chem Soc. 2002 May 1;124(17):4716-21. doi: 10.1021/ja0126226.

Abstract

A concise, stereocontrolled, and practical synthesis of a neuraminidase inhibitor consisting of a highly functionalized D-proline scaffold is described. Key features involve a stereocontrolled addition of a propiolate ester to a chiral nonracemic nitrone derived originally from D-serine and the manipulation of acyclic and cyclic motifs en route to the target in 12.8% overall yield over 22 steps. Several crystalline intermediates were suitable for single-crystal X-ray analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemical synthesis*
  • Crystallography, X-Ray
  • Enzyme Inhibitors / chemistry*
  • Molecular Structure
  • Neuraminidase / antagonists & inhibitors*
  • Orthomyxoviridae / enzymology
  • Pyrrolidines / chemical synthesis*
  • Stereoisomerism

Substances

  • A 315675
  • Antiviral Agents
  • Enzyme Inhibitors
  • Pyrrolidines
  • Neuraminidase