title: Synthesis and properties of 14-epi-1α,25-dihydroxy-19-nortachysterol and its 2-substituted derivatives.
abstract: As the first stable tachysterol analogs, 14-epi-19-nortachysterol and its 2-substituted derivatives were synthesized using the Stille coupling reaction between the A-ring precursor (three vinylstannanes) and the CD-ring vinyl trifrate. Among them, the 2-methylidene group was hydrogenated with Wilkinson's catalyst regioselectively to obtain 2α- and 2β-methyl analogs after separation; therefore, five new 14-epi-19- nortachysterols were constructed. All 14-epi-19-nortachysterols showed moderate to strong human vitamin D receptor (hVDR) binding affinity except the 2α-(3-hydroxypropoxy) substituted analog. X-ray cocrystallographic analysis of the [truncated hVDR]-[2-methyl-14-epi-19-nortachysterol] complex exhibited an unusual binding structure that has not been observed previously.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sawada
authors.affiliation: Faculty of Pharmaceutical Sciences, Teikyo University, Kaga, Itabashi-ku, Tokyo 173-8605, Japan. akittaka@pharm.teikyo-u.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kittaka
mesh_terms: D002762:Cholecalciferol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D011487:Protein Conformation; D018167:Receptors, Calcitriol / Q000737:chemistry* / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C583150:14-epi-2alpha-hydroxypropoxy-1alpha,25-dihydroxy-19-nortachysterol; D018167:Receptors, Calcitriol; D002762:Cholecalciferol