Synthesis and biological activity of (24E)- and (24Z)-26-hydroxydesmosterol

Bioorg Med Chem. 2013 Sep 15;21(18):5794-8. doi: 10.1016/j.bmc.2013.07.015. Epub 2013 Jul 17.

Abstract

Using 3β-hydroxychol-5-en-24-oic acid (4) as starting material, the diastereoisomeric allylic alcohols (24E)-26-hydroxydesmosterol (2) and (24Z)-26-hydroxydesmosterol (3) have been synthesised in six steps with 67% and 12% overall yield, respectively. Both of these isomers are found in newborn mouse brain where sterol synthesis is high. Unlike desmosterol (1), neither of these isomers is a ligand to the liver x receptors and thus represents a novel biological deactivation mechanism avoiding cholesterol synthesis.

Keywords: 26-Hydroxydesmosterol; Cholesterol; Desmosterol; Desmosterolosis; Steroids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Crystallography, X-Ray
  • Desmosterol / analogs & derivatives*
  • Desmosterol / chemical synthesis
  • Desmosterol / chemistry*
  • Isomerism
  • Liver X Receptors
  • Mice
  • Molecular Conformation
  • Orphan Nuclear Receptors / chemistry
  • Orphan Nuclear Receptors / metabolism

Substances

  • (24Z)-26-hydroxydesmosterol
  • Liver X Receptors
  • Orphan Nuclear Receptors
  • Desmosterol