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

• Published in: Chirality (New York, N.Y.) N.Y.), 1999, Vol.11 (9), p.701-706
• Main Authors: Odrzywolska, Małgorzata, Chodyński, Michał, Zorgdrager, Jan, Van De Velde, Jan-Paul, Kutner, Andrzej
• Format: Article
• Language: English
• Subjects: (24R)-1; (24R)-24; (24R)‐1,24,25‐ and (24S)‐1,24,25‐trihydroxycholecalciferols; (24R)‐24,25‐ and (24S),24,25‐dihydroxycholecalciferols; 25- and (24S); 25- and (24S)-1; 25-dihydroxycholecalciferols; 25-trihydroxycholecalciferols; Animals; binding affinity for vitamin D receptor; Calcifediol - chemical synthesis; Calcifediol - isolation & purification; Calcifediol - metabolism; Calcitriol - chemical synthesis; Calcitriol - isolation & purification; Calcitriol - metabolism; Cattle; chiral stationary phase HPLC; Chromatography, High Pressure Liquid - methods; diastereoselective α-hydroxylation; Magnetic Resonance Spectroscopy; Protein Binding; Receptors, Calcitriol - metabolism; Stereoisomerism
• ISSN: 0899-0042; 1520-636X
• DOI: 10.1002/(SICI)1520-636X(1999)11:9<701::AID-CHIR6>3.0.CO;2-L

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 α‐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. Chirality 11:701–706, 1999. © 1999 Wiley‐Liss, Inc.