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

✍ Scribed by Małgorzata Odrzywolska; Michał Chodyński; Jan Zorgdrager; Jan-Paul Van De Velde; Andrzej Kutner

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 132 KB
• Volume: 11
• Category: Article
• ISSN: 0899-0042
• DOI: 10.1002/(sici)1520-636x(1999)11:9<701::aid-chir6>3.0.co;2-l

✦ Synopsis

A series of analogs of 1,25-dihydroxycholecalciferol and 25hydroxycholecalciferol were obtained with an additional hydroxyl in the aliphatic side chain at carbon atom C-24. These analogs were synthesized by direct and diastereoselective ␣-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)-1,24,25trihydroxycholecalciferol for the calf thymus intracellular vitamin D receptor was one order of magnitude higher than that of the respective (24S)-diastereomer.