Synthesis of an Estradiol Derivative with an Adenosine-phosphate Mimic Linked at Position 16β
Amelie Talbot, Rene Maltais and Donald Poirier
Affiliation: Laboratory of Medicinal Chemistry, CHU de Quebec-Research Center and Laval University, 2705, Laurier Boulevard, Quebec, Quebec, G1V 4G2, Canada.
Keywords: Cofactor mimics, cross-metathesis reaction, enzyme substrate, estradiol derivative, hybrid inhibitor, steroid.
We describe the synthesis and characterization of three compounds targeting the enzyme 17β-hydroxysteroid dehydrogenase
type 1. The first one is a 4-aminobenzoyl-phenylacetic acid derivative designed as a mimic of adenosine-phosphate, the second one is an
estradiol derivative having a decyl side chain at position 16β, and the third one is a hybrid compound with the adenosine-phosphate
mimic covalently linked to the C16-estradiol side chain. Judicious use of key reactions such as Claisen rearrangement, microwave Grignard
alkylation, selective TEMPO oxidation and cross metathesis has been required to achieve these targeted molecules.
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