Synthesis of methoxyfumimycin with 1,2-addition to ketimines

J Org Chem. 2010 Jan 1;75(1):229-32. doi: 10.1021/jo902026s.

Abstract

The synthesis of (+/-)-methoxyfumimycin, a potential new bacterial peptide deformylase (PDF) inhibitor, is reported. To generate the stereogenic fully substituted carbon, the key step is a 1,2-addition of a methyl Grignard reagent to a ketimine. The overall synthetic strategy involves a Dakin oxidation of a vanillin derivative, Friedel-Crafts acylation, Claisen rearrangement, lactonization, and rhodium-catalyzed olefin isomerization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Benzaldehydes / chemistry*
  • Benzofurans / chemical synthesis*
  • Benzofurans / chemistry
  • Catalysis
  • Imines / chemical synthesis*
  • Imines / chemistry
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Nitriles / chemical synthesis*
  • Nitriles / chemistry
  • Rhodium / chemistry*
  • Stereoisomerism

Substances

  • Anti-Bacterial Agents
  • Benzaldehydes
  • Benzofurans
  • Imines
  • Nitriles
  • fumimycin
  • ketimine
  • vanillin
  • Rhodium