The Journal of Steroid Biochemistry and Molecular Biology | 2019

Synthesis and characterization of 20-hydroxyvitamin D3 with the A-ring modification



Two novel 20-hydroxyvitamin D3 analogues (4a,b) with the A-ring modification have been synthesized by a convergent manner. An alternative pathway of vitamin D3 metabolism by cytochrome P450scc CYP11A1 was reported to afford 20-hydroxyvitamin D3 (3), functions of which remain to be explored. Based on the structure of the 20-hydroxy metabolite, novel analogues (4a,b) with the modifications, including the 1α-hydroxy, 25-hydroxy and 2α-methyl groups, have been designed. The side chain of the requisite CD-ring portions (9a,b) was introduced by Grignard reaction as a key step, and the stereochemistry at the C20 position was confirmed by the X-ray crystal structure analysis of the synthetic intermediate (8b). Preliminary biological characterization using the bovine thymus vitamin D receptor suggested that the introduction of the active motifs into the 20-hydroxyvitamin D3 scaffold elevated the receptor affinity.

Volume 187
Pages 27-33
DOI 10.1016/j.jsbmb.2018.10.019
Language English
Journal The Journal of Steroid Biochemistry and Molecular Biology

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