Synthesis and properties of 14-epi-1α,25-dihydroxy-19-nortachysterol and its 2-substituted derivatives

Daisuke Sawada, Atsushi Kittaka

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

As the first stable tachysterol analogs, 14-epi-19-nortachysterol and its 2-substituted derivatives were synthesized using the Stille coupling reaction between the A-ring precursor (three vinylstannanes) and the CD-ring vinyl trifrate. Among them, the 2-methylidene group was hydrogenated with Wilkinson’s catalyst regioselectively to obtain 2α- and 2β-methyl analogs after separation; therefore, five new 14-epi-19-nortachysterols were constructed. All 14-epi-19-nortachysterols showed moderate to strong human vitamin D receptor (hVDR) binding affinity except the 2α-(3-hydroxypropoxy) substituted analog. X-ray cocrystallographic analysis of the [truncated hVDR]-[2-methyl-14-epi-19-nortachysterol] complex exhibited an unusual binding structure that has not been observed previously.

Original languageEnglish
Pages (from-to)2454-2459
Number of pages6
JournalCurrent Topics in Medicinal Chemistry
Volume14
Issue number21
DOIs
Publication statusPublished - Jan 1 2014

Keywords

  • 14-Epimerization
  • Crystal structure
  • Stille coupling
  • Tachysterol
  • Vitamin D
  • Vitamin D receptor

ASJC Scopus subject areas

  • Drug Discovery

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