Chemical Synthesis and Biological Activities of 20<i>S</i>,24<i>S</i>/<i>R</i>‑Dihydroxyvitamin D3 Epimers and Their 1α-Hydroxyl Derivatives

Bioactive vitamin D3 metabolites 20<i>S</i>,24<i>S</i>-dihydroxyvitamin D3 [20<i>S</i>,24<i>S</i>(OH)₂D3] and 20<i>S</i>,24<i>R</i>-dihydroxyvitamin D3 [20<i>S</i>,24R­(OH)₂D3] were chemically synthesized and confirmed to be identical to their enzymatically generated counterparts. The absolute configurations at C24 and its influence on the kinetics of 1α-hydroxylation by CYP27B1 were determined. Their corresponding 1α-hydroxyl derivatives were subsequently produced. Biological comparisons of these products showed different properties with respect to vitamin D3 receptor activation, anti-inflammatory activity, and antiproliferative activity, with 1α,20S,24R­(OH)₂D3 being the most potent compound