Recent developments for introducing a hexafluoroisopropanol unit into the Vitamin D side chain

J Steroid Biochem Mol Biol. 2018 Mar:177:250-254. doi: 10.1016/j.jsbmb.2017.07.008. Epub 2017 Jul 14.

Abstract

Among numerous studies on synthetic approaches to and the biological activities of vitamin D analogues, we herein focused on falecalcitriol, an analogue of calcitriol (1α,25-dihydroxyvitamin D3), in which a 26,26,26,27,27,27-hexafluoroisopropanol unit has been introduced into the side chain. Falecalcitriol was designed to escape from the metabolism of CYP24A1 and has been used as a drug to treat secondary hyperparathyroidism since 2001. Its metabolite, the 23-hydroxy form, retains biological activity and resistants to further metabolism. Recent developments in synthetic methodologies for introducing the hexafluoroisopropanol unit into the vitamin D CD-ring side chain were described herein.

Keywords: CD-ring; Falecalcitriol; Hexafluoroacetone (HFA); Hexafluoroisopropanol unit; Ruppert-Prakash reagent (CF(3)TMS); Synthesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetone / analogs & derivatives
  • Acetone / chemistry
  • Calcitriol / analogs & derivatives*
  • Calcitriol / chemistry
  • Fluorocarbons / chemistry
  • Propanols / chemistry*

Substances

  • Fluorocarbons
  • Propanols
  • Acetone
  • hexafluoroisopropanol
  • hexafluoroacetone
  • Calcitriol
  • 26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitamin D3