Synthesis and biological activity of the (25R)-cholesten-26-oic acids--ligands for the hormonal receptor DAF-12 in Caenorhabditis elegans

Org Biomol Chem. 2009 Mar 7;7(5):909-20. doi: 10.1039/b817358c. Epub 2009 Jan 27.

Abstract

We describe the stereoselective transformation of diosgenin (4a) to (25R)-Delta(4)-dafachronic acid (1a),(25R)-Delta(7)-dafachronic acid (2a), and (25R)-cholestenoic acid (3a), which represent potential ligands forthe hormonal receptor DAF-12 in Caenorhabditis elegans. Key-steps of our synthetic approach are amodified Clemmensen reduction of diosgenin (4a) and a double bond shift from the 5,6- to the 7,8-position. In the 25R-series, the Delta(7)-dafachronic acid 2a exhibits the highest hormonal activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / drug effects*
  • Cholestenes / chemical synthesis*
  • Cholestenes / pharmacology
  • Diosgenin / chemistry
  • Ligands
  • Receptors, Cytoplasmic and Nuclear / drug effects*
  • Structure-Activity Relationship

Substances

  • Caenorhabditis elegans Proteins
  • Cholestenes
  • DAF-12 protein, C elegans
  • Ligands
  • Receptors, Cytoplasmic and Nuclear
  • cholestenoic acid
  • Diosgenin