Synthesis and biological characterization of 1alpha,24,25-trihydroxy-2beta-(3-hydroxypropoxy)vitamin D(3) (24-hydroxylated ED-71)

Steroids. 2001 Mar-May;66(3-5):267-76. doi: 10.1016/s0039-128x(00)00149-5.

Abstract

24-Hydroxylated derivatives were synthesized in 24(R) and 24(S) forms by the convergent method as analogs related to 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D(3). In the convergent synthesis, the A-ring fragment, synthesized from diethyl D-tartarate, and the C/D-ring fragments in 24(R) and 24(S) forms (vitamin D numbering), obtained from vitamin D(2) via the Inhoffen-Lythgoe diol, were coupled in moderate yields to give 1alpha,24(R),25-trihydroxy-2beta-(3-hydroxypropoxy)vitamin D(3) and 1alpha,24(S),25-trihydroxy-2beta-(3-hydroxypropoxy)vitamin D(3). In preliminary biological evaluations, 24-hydroxylation of 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D(3) caused weakened affinity to vitamin D binding protein in vitro and less calcemic activity in vivo compared to the parent compound. While the affinity to vitamin D receptor in 24(R) epimer was sustained, the affinity in 24(S) epimer was less than that of the parent compound.

MeSH terms

  • Animals
  • Calcitriol / analogs & derivatives
  • Calcitriol / chemical synthesis*
  • Calcitriol / metabolism
  • Calcitriol / pharmacology
  • Calcium / metabolism
  • Carrier Proteins / metabolism
  • Chickens
  • Cholecalciferol / analogs & derivatives*
  • Cholecalciferol / chemical synthesis
  • Cholecalciferol / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Protein Binding
  • Rats
  • Receptors, Calcitriol / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship
  • Vitamin D / analogs & derivatives

Substances

  • Carrier Proteins
  • Receptors, Calcitriol
  • vitamin D binding protein 1, primate
  • Vitamin D
  • Cholecalciferol
  • Calcitriol
  • eldecalcitol
  • Calcium