Synthesis of 19-norcalcitriol analogs with pegylated alkylidene chains at C-2.

Graphical abstract Highlights • A-Ring fragment's synthesis started from cyclohexanone derived from quinic acid. • 19-Norcalcitriol analogs with pegylated 2-alkylidene groups were synthesized. • 2-Alkylidene chain is terminated by hydroxyl or 2-(pyridin-2′-yl)ethylamino group. • The affinities of the synthesized 19-norcalcitriol analogs to VDR were assessed. Abstract The results presented in this paper constitute an extension of our synthetic efforts focused on 19-norvitamin D compounds possessing elongated 2-alkylidene substituents. Based on our previous results, molecular modeling studies, and docking experiments, we selected a novel 19-norcalcitriol analog with long chain at C-2 containing several ether moieties and terminated by 2-(pyridin-2′-yl)ethylamino fragment. It was expected that such structural modification might allow binding of transition metal by the ligand, increase solubility of the formed complexes as well as improve their affinity to the VDR. For comparison, a 19-norcalcitriol analog was also obtained with the terminal hydroxyl group at its pegylated 2-alkylidene substituent. The synthesis of the target vitamin D compounds described in this work was performed using the Wittig-Horner approach. The respective A-ring phosphine oxide was obtained starting from the D -(-)-quinic acid and then coupled with the known Grundmann ketone. [ABSTRACT FROM AUTHOR]