Premium
Convergent synthesis, chiral HPLC, and vitamin D receptor affinity of analogs of 1,25‐dihydroxycholecalciferol
Author(s) -
Odrzywolska Małgorzata,
Chodyński Michał,
Halkes Sebastian J.,
Van De Velde JanPaul,
Fitak Hanna,
Kutner Andrzej
Publication year - 1999
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/(sici)1520-636x(1999)11:3<249::aid-chir12>3.0.co;2-v
Subject(s) - chemistry , diastereomer , calcitriol receptor , stereochemistry , chirality (physics) , carbanion , high performance liquid chromatography , ring (chemistry) , vitamin , vicinal , chiral column chromatography , receptor , enantiomer , organic chemistry , biochemistry , chiral symmetry , physics , quantum mechanics , nambu–jona lasinio model , quark
A series of analogs of 1,25‐dihydroxycholecalciferol was obtained with an additional chiral center at the terminus of the aliphatic side chain (C‐25). The analogs were obtained from (+)‐( R )‐ and (−)‐( S )‐2‐methylglycidols, by opening of the oxirane ring with the carbanions derived from vitamin D C 23a,24 ‐ or C 22 ‐sulfones. The diastereomeric purity of the analogs was determined by high‐performance liquid chromatography on a chiral stationary phase. The binding affinity of analogs for the calf thymus intracellular vitamin D receptor (VDR) was two orders of magnitude lower than that of the lead compound of this group, 24a,24b‐dihomo‐1,25‐dihydroxycholecalciferol, and it was comparable to the affinity of analogs of 24‐nor‐1,25‐dihydroxycholecalciferol. However, a twofold difference was observed for analogs diastereomeric at C‐25 in their affinity for VDR. The diastereodifferentiation of the binding affinity was found to be specific for vitamin D vicinal 25,26‐diols as it disappears for analogs where 26‐hydroxyl, neighboring the C‐25 chiral center, is replaced with methyl. Chirality 11:249–255, 1999. © 1999 Wiley‐Liss, Inc.