Calcitriol derivatives with two different side chains at C-20. 24-hydroxy derivatives as metabolic products and molecular probes for VDR exploration

The Journal of Steroid Biochemistry and Molecular Biology
Hubert MaehrLuciano Adorini

Abstract

We previously synthesized calcitriol derivatives with two identical side chains emanating at C-20, also known as gemini. In view of the evidence identifying C-24 hydroxylation as the first step in the in the metabolic cascade of calcitriol and gemini, stereochemical differentiation between the possible epimeric 20R- and 20S side-chain hydroxylated gemini became of interest. We now report the stereoselective synthesis of these compounds. Of these, 1,24(R),25-trihydroxy-21-(3-hydroxy-3-methyl-butyl)-20(R)-19-nor-cholecalciferol was identified as the main metabolic product of 19-nor-gemini. In general, higher doses of the 24-hydroxylated gemini compounds were required to increase blood calcium levels in mice and to suppress INF-gamma release in MLR.

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Citations

Feb 3, 2006·Natural Product Reports·James R Hanson
Feb 22, 2017·Acta Crystallographica. Section E, Crystallographic Communications·Andrea MartínezYagamare Fall Diop
Jun 22, 2013·ChemMedChem·Can-Fei ZhangZhao-Peng Liu

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