1. Synthesis of novel 19-norvitamin D3 analogs with unnatural triene system
- Author
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Urszula Kulesza, Rafal R. Sicinski, Lori A. Plum, Hector F. DeLuca, and Antonio Mouriño
- Subjects
Ketone ,Transcription, Genetic ,Stereochemistry ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Drug Evaluation, Preclinical ,HL-60 Cells ,Chemistry Techniques, Synthetic ,Conjugated system ,Sigmatropic reaction ,Biochemistry ,Structure-Activity Relationship ,chemistry.chemical_compound ,Endocrinology ,Calcitriol ,Animals ,Humans ,Moiety ,Molecular Biology ,chemistry.chemical_classification ,Enyne ,Chemistry ,Synthon ,Regioselectivity ,Cell Differentiation ,Cell Biology ,Rats ,Receptors, Calcitriol ,Molecular Medicine ,Derivative (chemistry) - Abstract
9-Alkylidene analogs of 19-nor-1α,25-(OH) 2 D 3 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’.
- Published
- 2013
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