Concise route to the chiral pyrrolidine core of selective inhibitors of neuronal nitric oxide

Org Lett. 2009 Nov 19;11(22):5194-7. doi: 10.1021/ol902109t.

Abstract

2-(((3R,4R)-4-(Allyloxy)-1-benzylpyrrolidin-3-yl)methyl)-6-(2,5-dimethyl-1H-pyrrol-1-yl)-4-methylpyridine (2), a key intermediate for the preparation of novel neuronal nitric oxide synthase (nNOS) inhibitors, is synthesized using diisopropyl (R)-(+)-malate as the starting material. The key steps involve a Frater-Seebach diastereoselective alkylation and a fast intramolecular cyclization.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alkylation
  • Allyl Compounds / chemical synthesis
  • Allyl Compounds / chemistry
  • Allyl Compounds / pharmacology*
  • Cyclization
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Molecular Conformation
  • Nitric Oxide Synthase Type I / antagonists & inhibitors*
  • Pyridines / chemical synthesis
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Allyl Compounds
  • Enzyme Inhibitors
  • Pyridines
  • Nitric Oxide Synthase Type I