Non-canonical regioisomerizations and a 'Diels-Alderase' are likely essential in the biosynthesis of spiculoic acid A

Bioorg Med Chem Lett. 2012 Aug 15;22(16):5253-6. doi: 10.1016/j.bmcl.2012.06.052. Epub 2012 Jun 23.

Abstract

The regiochemistry of dehydration and cyclization steps of the linear biosynthetic precursor of the polyketide natural product Spiculoic acid A (1) were examined. Herein we describe the synthesis of polyene-containing aldehyde 21, a counterpart to the metabolite's putative polyketide intermediate and demonstrate its inability to undergo facile IMDA chemistry. These results suggest the involvement of a non-canonical regioisomerization in the biosynthesis of 1, and that the IMDA reaction is likely enzyme-catalyzed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biocatalysis
  • Carboxylic Acids / chemistry
  • Carboxylic Acids / metabolism*
  • Cyclization
  • Indans / chemistry
  • Indans / metabolism*
  • Polyketide Synthases / metabolism*
  • Stereoisomerism

Substances

  • Carboxylic Acids
  • Indans
  • spiculoic acid A
  • Polyketide Synthases