Synthesis Of 1,2,3-Triazole Vitamin D Derivatives Based On Click Reaction

Vitamin D₂ has been studied widely for its metabolites in the body, it can not only maintain calcium and phosphorus homeostasis but also affect other pathologica or physiological processes such as differentiation of various cell types and regulation of the proliferation. Owing to its remarkable physiological function in the treatment and prevention of various diseases, a large number of vitamin D₂ derivatives have been synthesized by chemical methods.In this paper, triazole vitamin D₂ and CD ring triazole compounds were synthesized by OTs protected hydroxyl, SB2 reaction and click from vitamin D₂. On the other hand, 1α-hydrox y-20-oxime vitamin D derivatives was prepared by using compound 4.1 as raw material through four steps. The main contents are as follows:（1） In this paper, a method applied to synthesize vitamin D₂ derivativesa was designed, which has advantages of short route, mild reaction conditions and accessible reagent. Eight vitamin D₂ compounds were prepared with 1,2,3-triazole group on A ring. The reactions included sulfonylation reaction, substitution reaction and click reaction.（2） Six novel triazole analogues in the side chain of vitamin D were synthesized by using vitamin D₂ as material via four steps,which included Ozone oxidation, hydroxyl protection, SN2 reaction and 1,3-dipolar cycloaddition.（3） A new vitamin D analogue was synthesized by using compound 4.1 as raw material via four steps, which included oxidation, oximation reaction, photocatalytic reaction and deprotecti on of hydroxyl group.（4） According to MTT experiment, the six compounds （2.3a,2.3b,2.3e,3.3a,3.3d,3.3e） were tested on MCF-7 cells to study the antiproliferation activity in a dose dependent manner. All compounds exhibited good antiproliferation activities to MCF-7 cells.