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 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.
Martin
René
R
Department Chemie, Technische Universität Dresden, Bergstrasse 66, 01069 Dresden, Germany.
Schmidt
Arndt W
AW
Theumer
Gabriele
G
Krause
Tilo
T
Entchev
Eugeni V
EV
Kurzchalia
Teymuras V
TV
Knölker
Hans-Joachim
HJ
D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000187:drug effects*; D002782:Cholestenes / Q000138:chemical synthesis* / Q000494:pharmacology; D004144:Diosgenin / Q000737:chemistry; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects*; D013329:Structure-Activity Relationship
D029742:Caenorhabditis elegans Proteins; D002782:Cholestenes; C410905:DAF-12 protein, C elegans; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; C514718:cholestenoic acid; D004144:Diosgenin