Biology-oriented synthesis of stereochemically diverse natural-product-derived compound collections by iterative allylations on a solid support

Chemistry. 2007;13(12):3305-19. doi: 10.1002/chem.200601698.

Abstract

A strategy aiming at the introduction of stereocenters into polymer-bound natural-product-derived and -inspired compound collections is presented. Treatment of immobilized aldehydes with Brown's pinene-derived allylboranes results in the stereoselective formation of homoallylic alcohols with up to 89 % ee (ee=enantiomeric excess). Subsequent iterative ozonolysis-allylation sequences with up to three allylations on a solid support give access to 1,3-polyols with different relative configurations. Esterification with acryloyl chloride and final ring-closing metathesis yields alpha,beta-unsaturated delta-lactones with multiply oxygenated side chains, a substructure found in a group of natural products with a broad range of biological activity. The flexibility of the approach is exemplified by the parallel synthesis of all eight diastereomers of cryptocarya diacetate on a solid support. The individual isomers are obtained in overall yields of 40-60 % over 10 steps and with 63-85 % diastereoselectivity for the major isomer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allyl Compounds / chemistry*
  • Biological Products / chemical synthesis*
  • Combinatorial Chemistry Techniques*
  • Cyclization
  • Lactones / chemical synthesis*
  • Models, Chemical
  • Molecular Mimicry
  • Polymers / chemical synthesis*
  • Stereoisomerism

Substances

  • Allyl Compounds
  • Biological Products
  • Lactones
  • Polymers
  • polyol