Synthesis and Biological Evaluation of Vitamin D3 Metabolite 20S,23S-Dihydroxyvitamin D3 and Its 23R Epimer

  • J Med Chem. 2016 May 26;59(10):5102-8. doi: 10.1021/acs.jmedchem.6b00182.
Zongtao Lin  1 ,  Srinivasa R Marepally  1 ,  Dejian Ma  1 ,  Tae-Kang Kim  2 ,  Allen Sw Oak  2 ,  Linda K Myers  3 ,  Robert C Tuckey  4 ,  Andrzej T Slominski  2  5 ,  Duane D Miller  1 ,  Wei Li  1
Affiliations
  • 1. Department of Pharmaceutical Sciences, University of Tennessee Health Science Center , 881 Madison Avenue, Room 561, Memphis, Tennessee 38163, United States.
  • 2. Department of Dermatology, University of Alabama at Birmingham , Birmingham, Alabama 35294, United States.
  • 3. Department of Medicine, University of Tennessee Health Science Center , Memphis, Tennessee 38163, United States.
  • 4. School of Chemistry and Biochemistry, University of Western Australia , Crawley, Western Australia 6009, Australia.
  • 5. VA Medical Center at Birmingham , Birmingham, Alabama 35294, United States.
PMID: 27070779 DOI: 10.1021/acs.jmedchem.6b00182
Abstract

The vitamin D3 metabolite, 20S,23S-dihydroxyvitamin D3, was chemically synthesized for the first time and identified to be the same as the enzymatically produced metabolite. The C23 absolute configurations of both 20S,23S/R-dihydroxyvitamin D3 epimers were unambiguously assigned by NMR and Mosher ester analysis. Their kinetics of CYP27B1 metabolism were investigated during the production of their 1α-hydroxylated derivatives. Bioactivities of these products were compared in terms of vitamin D3 receptor activation, anti-inflammatory, and antiproliferative activities.