Synthesis and Properties of 14-epi-1α,25-Dihydroxy-19-Nortachysterol and its 2-Substituted Derivatives

Title:Synthesis and Properties of 14-epi-1α,25-Dihydroxy-19-Nortachysterol and its 2-Substituted Derivatives

Volume: 14 Issue: 21

Author(s): Daisuke Sawada and Atsushi Kittaka

Affiliation:

Keywords: Crystal structure, 14-Epimerization, Stille coupling, Tachysterol, Vitamin D₃, Vitamin D receptor.

Abstract: As the first stable tachysterol analogs, 14-epi-19-nortachysterol and its 2-substituted derivatives were synthesized using the Stille coupling reaction between the A-ring precursor (three vinylstannanes) and the CD-ring vinyl trifrate. Among them, the 2-methylidene group was hydrogenated with Wilkinson’s catalyst regioselectively to obtain 2α- and 2β-methyl analogs after separation; therefore, five new 14-epi-19- nortachysterols were constructed. All 14-epi-19-nortachysterols showed moderate to strong human vitamin D receptor (hVDR) binding affinity except the 2α-(3-hydroxypropoxy) substituted analog. X-ray cocrystallographic analysis of the [truncated hVDR]-[2-methyl-14-epi-19-nortachysterol] complex exhibited an unusual binding structure that has not been observed previously.

Cite this article as:

Sawada Daisuke and Kittaka Atsushi, Synthesis and Properties of 14-epi-1α,25-Dihydroxy-19-Nortachysterol and its 2-Substituted Derivatives, Current Topics in Medicinal Chemistry 2014; 14 (21) . https://dx.doi.org/10.2174/1568026615666141208103741