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

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

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.

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