Synthesis of 19-norcalcitriol analogs with alkylidene moieties at C-2 based on succinic acid and l-methionine

Abstract

On the basis of the literature data, our previous research work and docking experiments, we designed novel 19-norvitamin D compounds having elongated 2-alkylidene substituents. These 19-norcalcitriol derivatives have attached 2-(3'-aminopropylidene) substituent in which the nitrogen atom bears acyl residue derived from succinic acid and l-methionine. Both compounds were obtained by the same synthetic strategy involving Julia coupling of the A-ring ketone with the known C/D-ring sulfone. In the obtained 1α,25-dihydroxy-19-norvitamin D₃ derivative, the alkylidene substituent at C-2 was further elaborated to the desired structures.

Keywords: 19-Norcalcitriol; Julia olefination; Secosteroids; Vitamin D receptor.