Synthesis and biological activity of 1a,2a,25-Trihydroxyvitamin D3: Active metabolite of 2a-(3-Hydroxypropoxy)-1a,25-dihydroxyvitamin D3 by human CYP3A4

Masashi Takano, Saori Ohya, Kaori Yasuda, Miyu Nishikawa, Akiko Takeuchi, Daisuke Sawada, Toshiyuki Sakaki, Atsushi Kittaka

Research output: Contribution to journalArticle

8 Citations (Scopus)


Our previous studies revealed that recombinant human CYP3A4 converted 2a-(3-hydroxypropoxy)-1a,25- dihydroxyvitamin D3 (O2C3), which was a more potent binder to vitamin D receptor (VDR) than the natural hormone, 1a,25-dihydroxyvitamin D3 (1a,25(OH)2D3, 1), to 1a,2a,25-trihydroxyvitamin D3 (2). Here, we synthesized 2 using the Trost Pd-mediated coupling reaction between an A-ring precursor and a CD-ring bromoolefin and evaluated its preliminary biological activity. We found that metabolite 2 from O2C3 was still active as a VDR ligand while maintaining human VDR binding affinity (27.3% of 1a,25(OH)2D3) and HL-60 cell differentiation activity (62% of 1a,25(OH)2D3).

Original languageEnglish
Pages (from-to)182-184
Number of pages3
JournalChemical and Pharmaceutical Bulletin
Issue number2
Publication statusPublished - Feb 1 2014
Externally publishedYes



  • 1a,2a,25-trihydroxyvitamin D3
  • CYP24A1
  • CYP3A4
  • Cell differentiation
  • Vitamin D receptor

ASJC Scopus subject areas

  • Chemistry(all)
  • Drug Discovery

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