Total synthesis of aculeatin A via double intramolecular oxa-Michael addition of secondary/tertiary alcohols

J Org Chem. 2014 Feb 7;79(3):1498-504. doi: 10.1021/jo4026868. Epub 2014 Jan 14.

Abstract

A new synthetic strategy was developed for a concise total synthesis of aculeatin A as a single spiroisomer in both racemic and enantioselective fashions in 8-10 steps with ∼10% overall yield from the known alkyne 11, featuring phenol oxidative dearomatization, double intramolecular oxa-Michael addition of secondary/tertiary alcohols, and chemo- and stereoselective reduction of ketone. The new synthetic strategy greatly expedites the access to the potent antiprotozoal aculeatin A, 6-epi-aculeatin D, and their analogues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohols / chemistry*
  • Cyclization
  • Cyclohexanones / chemical synthesis*
  • Cyclohexanones / chemistry
  • Oxidation-Reduction
  • Spiro Compounds / chemical synthesis*
  • Spiro Compounds / chemistry
  • Stereoisomerism

Substances

  • 1,7-dioxa-dispiro(5.1.5.2)pentadeca-9,12-dien-11-one
  • Alcohols
  • Cyclohexanones
  • Spiro Compounds
  • aculeatin A