Stereo- and Regiocontrolled Syntheses of Exomethylenic Cyclohexane β-Amino Acid Derivatives

Molecules. 2015 Nov 27;20(12):21094-102. doi: 10.3390/molecules201219749.

Abstract

Cyclohexane analogues of the antifungal icofungipen [(1R,2S)-2-amino-4-methylenecyclopentanecarboxylic acid] were selectively synthesized from unsaturated bicyclic β-lactams by transformation of the ring olefinic bond through three different regio- and stereocontrolled hydroxylation techniques, followed by hydroxy group oxidation and oxo-methylene interconversion with a phosphorane. Starting from an enantiomerically pure bicyclic β-lactam obtained by enzymatic resolution of the racemic compound, an enantiodivergent procedure led to the preparation of both dextro- and levorotatory cyclohexane analogues of icofungipen.

Keywords: Wittig reaction; amino acids; hydroxylation; icofungipen; selectivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry*
  • Antifungal Agents / chemical synthesis*
  • Antifungal Agents / pharmacology
  • Cyclohexanes / chemistry*
  • Cycloleucine / analogs & derivatives
  • Fungi / drug effects*
  • Hydroxylation
  • Molecular Structure
  • Oxidation-Reduction
  • beta-Lactams / chemistry*

Substances

  • Amino Acids
  • Antifungal Agents
  • Cyclohexanes
  • beta-Lactams
  • Cycloleucine
  • Cyclohexane
  • 2-amino-4-methylenecyclopentane-1-carboxylic acid