%0 Journal Article %J The Journal of Steroid Biochemistry and Molecular Biology %D 2004 %T 2-Methylene analogs of 1alpha-hydroxy-19-norvitamin D3: synthesis, biological activities and docking to the ligand binding domain of the rat vitamin D receptor %A Pawel Grzywacz %A Lori A. Plum %A Wanda Sicinska %A Rafal R. Sicinski %A Jean M. Prahl %A Hector F. DeLuca %K Animals %K Binding Sites %K Calcitriol %K Female %K HL-60 Cells %K Humans %K Hydrocarbons %K Ligands %K Methane %K Mice %K Models, Molecular %K Rats %K Receptors, Calcitriol %X In continuing efforts towards the synthesis of biologically active vitamin D compounds of potential therapeutic value, new 2-methylene-1alpha-hydroxy-19-norvitamin D(3) analogs 3 and 4 with modified alkyl side chains have been synthesized. The key synthetic step involved Lythgoe-type Wittig-Horner coupling of Windaus-Grundmann type ketones 9, possessing different 17beta-alkyl substituents, with the phosphine oxide 10 prepared from (-)-quinic acid. The prepared vitamins 3 and 4 were ca. eight times less potent than 1alpha,25-dihydroxyvitamin D(3) (1alpha,25-(OH)(2)D(3)) (1) in binding to the rat intestinal vitamin D receptor (VDR). In comparison with the hormone 1 they exhibited slightly lower cellular HL-60 differentiation activity. When tested in vivo; the analog 3 was characterized by very high bone calcium mobilizing potency and intestinal calcium transport activity. Unexpectedly, the 25-methyl compound 4 showed marked calcemic activity in both assays. Computational docking of the vitamin 3 into the binding pocket of the rat vitamin D receptor is also reported. %B The Journal of Steroid Biochemistry and Molecular Biology %V 89-90 %P 13-7 %8 2004 May %G eng %N 1-5 %R 10.1016/j.jsbmb.2004.03.103