Synthesis of novel 19-norvitamin D3 analogs with unnatural triene system.

The Journal of steroid biochemistry and molecular biology

PubMedID: 23270753

Kulesza U, Mouriño A, Plum LA, Deluca HF, Sicinski RR. Synthesis of novel 19-norvitamin D3 analogs with unnatural triene system. J Steroid Biochem Mol Biol. 2013;13623-6.
9-Alkylidene analogs of 19-nor-1a,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 9a-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'.