Diastereoselective synthesis, binding affinity for vitamin D receptor, and chiral stationary phase chromatography of hydroxy analogs of 1,25-dihydroxycholecalciferol and 25-hydroxycholecalciferol

Chirality. 1999;11(9):701-6. doi: 10.1002/(SICI)1520-636X(1999)11:9<701::AID-CHIR6>3.0.CO;2-L.

Abstract

A series of analogs of 1,25-dihydroxycholecalciferol and 25-hydroxycholecalciferol were obtained with an additional hydroxyl in the aliphatic side chain at carbon atom C-24. These analogs were synthesized by direct and diastereo-selective alpha-hydroxylation of enolates derived from respective vitamin D esters using Davies chiral oxaziridines. The use of (+)-(2R,8aS)-(8, 8-dichlorocamphoryl)sulfonyl oxaziridine resulted in (R) stereochemistry of the new asymmetric center for both series of analogs. Similarly, (-)-(2S,8aR) oxaziridine gave (S) analogs. The diastereomeric purity of hydroxy analogs was determined by high-performance liquid chromatography on a chiral stationary phase. High diastereopurity of hydroxylation of vitamin D esters was obtained without the use of any chiral auxiliary. The binding affinity of (24R)-1,24,25-trihydroxycholecalciferol for the calf thymus intracellular vitamin D receptor was one order of magnitude higher than that of the respective (24S)-diastereomer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcifediol / chemical synthesis*
  • Calcifediol / isolation & purification
  • Calcifediol / metabolism
  • Calcitriol / chemical synthesis*
  • Calcitriol / isolation & purification
  • Calcitriol / metabolism
  • Cattle
  • Chromatography, High Pressure Liquid / methods*
  • Magnetic Resonance Spectroscopy
  • Protein Binding
  • Receptors, Calcitriol / metabolism*
  • Stereoisomerism

Substances

  • Receptors, Calcitriol
  • Calcitriol
  • Calcifediol