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Synthesis and Hormonal Activity of the (25 S )‐Cholesten‐26‐oic Acids – Potent Ligands for the DAF‐12 Receptor in Caenorhabditis elegans
Author(s) -
Martin René,
Entchev Eugeni V.,
Däbritz Frank,
Kurzchalia Teymuras V.,
Knölker HansJoachim
Publication year - 2009
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200900443
Subject(s) - chemistry , stereocenter , ligand (biochemistry) , caenorhabditis elegans , stereochemistry , aldol reaction , stereoselectivity , receptor , hormone , biological activity , yield (engineering) , biochemistry , in vitro , enantioselective synthesis , catalysis , gene , materials science , metallurgy
Using a highly stereoselective Evans aldol reaction for the introduction of the stereogenic center at C‐25, we describe an efficient synthesis of the orthogonally diprotected (25 S )‐26‐hydroxycholesterol 11 . In a few synthetic steps, this crucial intermediate 11 has been converted into the four (25 S )‐cholesten‐26‐oic acids 1 – 4 , which have been obtained in 12–15 steps and 19–53 % overall yield based on commercially available 3β‐hydroxychol‐5‐en‐24‐oic acid ( 5 ). Our biological studies of the compounds 1 – 4 reveal that (25 S )‐Δ 7 ‐dafachronic acid ( 1 ) represents the most active steroidal ligand for the hormonal receptor DAF‐12 in Caenorhabditis elegans . Moreover, the saturated (25 S )‐dafachronic acid ( 3 ) represents a new ligand for this receptor and the (25 S )‐steroidal acids are more active as compared to their corresponding (25 R )‐counterparts.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)