title: Asymmetric catalytic ene-cyclization approach to 2-fluoro-19-nor-1,25-dihydroxyvitamin D(3) A-ring analog with significant transactivation activity.
abstract: 1alpha,25-Dihydroxyvitamin D(3) (1alpha,25(OH)2D3) has been shown to modulate not only proliferation and differentiation, but also apoptosis in malignant cells, indicating that it could be useful for the treatment of cancer and psoriasis. However, little information has been available on the binding conformation of the 1alpha,25(OH)2D3 molecule and its analogs with the vitamin D receptor (VDR). Therefore, we synthesized 2alpha-fluorinated A-ring analogs of 19-nor-1alpha,25(OH)2D3 in order to investigate the VDR-binding conformation of the A-rings on the basis of the (19)F NMR analysis. The 2alpha-fluoro-19-nor-1alpha,25-dihydroxyvitamin D3 A-ring analog thus synthesized via a asymmetric catalytic carbonyl-ene cyclization, shows significant activity in transactivation.
authors.affiliation: Department of Chemical Technology, Tokyo Institute of Technology, Tokyo 152-8552, Japan. kmikami@o.cc.titech.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Mikami
authors.forename: S
authors.initials: S
authors.lastname: Ohba
authors.forename: H
authors.initials: H
authors.lastname: Ohmura
authors.forename: N
authors.initials: N
authors.lastname: Kubodera
authors.forename: K
authors.initials: K
authors.lastname: Nakagawa
authors.forename: T
authors.initials: T
authors.lastname: Okano
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008968:Molecular Conformation; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics; D011487:Protein Conformation; D051381:Rats; D018167:Receptors, Calcitriol / Q000737:chemistry / Q000378:metabolism; D015534:Trans-Activators / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: C432643:2-fluoro-19-nor-1,25-dihydroxyvitamin D3; D000970:Antineoplastic Agents; D018167:Receptors, Calcitriol; D015534:Trans-Activators; D002117:Calcitriol