Synthesis of putative metabolites of 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D(3) (ED-71)

Steroids. 2006 Jul;71(7):529-40. doi: 10.1016/j.steroids.2005.11.001. Epub 2006 Apr 25.

Abstract

1alpha,25-Dihydroxy-2beta-(3-hydroxypropoxy)vitamin D(3) (ED-71), an analog of active vitamin D(3), 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] is under phase III clinical trials in Japan for the treatment of osteoporosis and bone fracture prevention. Since ED-71 has a substituent at the 2beta-position of the A-ring, it is recognized that the metabolic pathway of ED-71 might be more complicated than 1,25(OH)(2)D(3) because of metabolism at the 2beta-position substituent in addition to the inherent metabolism of the side chain. To clarify the metabolism of hydroxypropoxy substituent of the 2beta-positon and a combination of metabolism between side chain and 2beta-positon, four putative metabolites of ED-71 have been prepared as authentic samples. The metabolites at the 2beta-positon, the methyl ester derivative considered as an ester standard of the oxidized metabolite and the tetraol derivative as the truncated metabolite were synthesized from alpha-epoxide, a key intermediate of ED-71 synthesis. The combination metabolites between side chain and 2beta-positon, the 24(S)- and 24(R)-pentaols were synthesized using Trost's convergent method.

MeSH terms

  • Bone Density Conservation Agents / chemical synthesis*
  • Bone Density Conservation Agents / chemistry
  • Bone Density Conservation Agents / metabolism
  • Calcitriol / analogs & derivatives*
  • Calcitriol / chemical synthesis
  • Calcitriol / chemistry
  • Calcitriol / metabolism
  • Isomerism
  • Oxidation-Reduction
  • Vitamin D / analogs & derivatives

Substances

  • Bone Density Conservation Agents
  • Vitamin D
  • Calcitriol
  • eldecalcitol