title: Synthesis of novel 19-norvitamin D3 analogs with unnatural triene system.
abstract: 9-Alkylidene analogs of 19-nor-1α,25-(OH)2D3 were synthesized, possessing a 'reversed' triene system compared to the natural hormone. The conjugated triene moiety of the novel analogs was constructed by coupling an enyne anion, representing an A-ring synthon, with a 9α-substituted Grundmann ketone derivative. Regioselective dehydration followed by semihydrogenation under Lindlar conditions, provided the desired 9-alkylated 19-norprevitamins which were thermally isomerized to the corresponding 9-methylene and 9-ethylidene analogs of 19-norcalcitriol. It was established that only the former compound had significant binding affinity to the full-length recombinant rat vitamin D receptor. The remaining in vitro studies show very low activity of both analogs. This article is part of a Special Issue entitled 'Vitamin D Workshop'.
authors.affiliation: Department of Chemistry, University of Warsaw, 02-093 Warsaw, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Kulesza
authors.forename: Antonio
authors.initials: A
authors.lastname: Mouriño
authors.forename: Lori A
authors.initials: LA
authors.lastname: Plum
authors.forename: Hector F
authors.initials: HF
authors.lastname: Deluca
authors.forename: Rafal R
authors.initials: RR
authors.lastname: Sicinski
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D004353:Drug Evaluation, Preclinical; D018922:HL-60 Cells; D006801:Humans; D051381:Rats; D018167:Receptors, Calcitriol / Q000378:metabolism; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D018167:Receptors, Calcitriol; D002117:Calcitriol