Synthesis, Structure And Biological Evaluation Of Vitamin D₂ Oxime Derivatives

Currently, vitamin D structural modification is a hot research on vitamin D. Its analogs have been used in clinical treatment as drugs, such as Calcitriol, Tacalcitol and Doxercalciferol, etc. These compounds arouse us great interest by its good biocompatible and bioactive. We modify the structure of vitamin D by chemical methods to get seven kinds of novel vitamin D derivatives and nanomedicine precursors. What’ more, we take a preliminary exploration on their anticancer activity.First of all, by using 1(S),3(R)-Bis-(tert-butyldimethylsilyloxy)-20(S)-formyl-9, 10-secopregna-5(E),7(E),10(19)-triene as raw material, novel oxime and O-methyl ether analogues in the side chain of vitamin D are prepared through five steps including Wittig-Horner or Wittig reaction, reduction reaction, oximation reaction, deprotection of hydroxyl group and photocatalytic reaction. Then we use the semi-preparative HPLC to pure target compounds. What’s more, we get oxime and O-methyl ether analogues at A ring of vitamin D through Oppenauer oxidation and oximation. Last, we have conjugated clinically used drugs amantadine and vitamin D2 with vitamin D2 using a succinic acid linker. They are nanovectors precursors having potential bioactive.Finally, we initially explore these derivatives’inhibitory activity against cancer cells. We test these derivatives on human liver cancer cell(Hep G2) and human breast cancer cell(MCF-7) in a dose dependent manner to show their potential in cancer therapeutics.