Enantioselective synthesis of pyranonaphthoquinone antibiotics using a CBS reduction/cross-metathesis/oxa-Michael strategy

Org Biomol Chem. 2011 Aug 7;9(15):5423-30. doi: 10.1039/c1ob05595j. Epub 2011 Jun 8.

Abstract

The enantioselective syntheses of deoxydihydrokalafungin (5), cis-deoxydihydrokalafungin (6) and deoxykalafungin (7) are reported. The strategy was based on 4 key reactions: (1) CBS reduction of prochiral ketone 10 to introduce chirality at C-1, (2) radical allylation of quinone 9a, (3) cross-metathesis of dimethoxynaphthalene 13 with methyl acrylate, and (4) intramolecular oxa-Michael addition of alcohol 8 to form the core naphthopyran ring system. This novel approach delivers naphthopyrans possessing the natural trans-stereochemistry observed in the pyranonaphthoquinone family of antibiotics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Molecular Structure
  • Naphthoquinones / chemical synthesis*
  • Naphthoquinones / chemistry
  • Oxidation-Reduction
  • Pyrans / chemical synthesis*
  • Pyrans / chemistry
  • Stereoisomerism

Substances

  • Anti-Bacterial Agents
  • Naphthoquinones
  • Pyrans