title: Synthetic strategy and biological activity of A-ring stereoisomers of 1,25- dihydroxyvitamin D3 and C2-modified analogues.
abstract: The hormonally active form of vitamin D3, 1α,25-dihydroxyvitamin D3 (1a), has a wide variety of biological activities and its major molecular target is considered to be the vitamin D receptor (VDR). The A-ring stereoisomers of 1a as well as its C2-modified analogues, which have different stereochemistry at the C1 and/or C3 hydroxy groups, are of interest since recent metabolic studies have shown that catabolism could occur through A-ring modification. In this review, a practical and versatile synthesis of the A-ring enyne precursors by the convergent method of Trost and coworkers, which is needed to construct all possible A-ring stereoisomers of 1,25-dihydroxyvitamin D3 (1a-d), and the C2-modified analogues (4a-d, 5a-d, 6a-d and 7a-d) is described. A strategy for the synthesis and evaluation of all possible A-ring stereoisomers of 1a and their A-ring modified analogues is important, and this will stimulate synthesis and biological studies into vitamin D.
authors.forename: Toshie
authors.initials: T
authors.lastname: Fujishima
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Suenaga
authors.affiliation: Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, Shido, Sanuki, Kagawa 769-2193, Japan. tofu@kph.bunri-u.ac.jp.
authors.forename: Takato
authors.initials: T
authors.lastname: Nozaki
mesh_terms: D000818:Animals; D004100:Dihydroxycholecalciferols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular
chemical_list: D004100:Dihydroxycholecalciferols; C023850:1 alpha,24-dihydroxyvitamin D3