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

  • J Med Chem. 2015 Oct 8;58(19):7881-7. doi: 10.1021/acs.jmedchem.5b00881.
Zongtao Lin ,  Srinivasa Reddy Marepally ,  Dejian Ma ,  Linda K Myers ,  Arnold E Postlethwaite  1 ,  Robert C Tuckey  2 ,  Chloe Y S Cheng  2 ,  Tae-Kang Kim  3 ,  Junming Yue ,  Andrzej T Slominski  3  4 ,  Duane D Miller ,  Wei Li
Affiliations
  • 1. Department of Veterans Affairs Medical Center, Memphis, Tennessee 38104, United States.
  • 2. School of Chemistry and Biochemistry, University of Western Australia , Crawley, WA 6009, Australia.
  • 3. Department of Dermatology, University of Alabama at Birmingham , Birmingham, Alabama 35294, United States.
  • 4. VA Medical Center at Birmingham, Birmingham, Alabama 35294, United States.
PMID: 26367019 DOI: 10.1021/acs.jmedchem.5b00881
Abstract

Bioactive vitamin D3 metabolites 20S,24S-dihydroxyvitamin D3 [20S,24S(OH)2D3] and 20S,24R-dihydroxyvitamin D3 [20S,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.