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

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 for the hormonal receptor DAF-12 in Caenorhabditis elegans. Key-steps of our synthetic approach are a modified 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.