The Exploitation And Optimization Of The Synthetic Technics Of Calcipotriol-A Pharmaceutical That Has Been Used To Treat Psoriasis

Objective: Calcipotriol has been used as a pharmaceutical to treat psoriasis, which has been synthesized first by Calverley in 1988. There are some difficulties and technical requirements to synthesize it, due to its long synthetic route, the formation and configuration transformation of one or more chiral centers were involved in the synthetic process. It is difficult to produce the pharmaceutical according to the reported methods, for patent protection and technical security; till now there are few companies manufactured this medicament in China. So there is good foreground and commercial value to empolder it. In order to simplify the routes, reduce the cost and increase the yields, we have empoldered the pharmaceutical on the basis of Calverlers' works with the aim of achieving the industrial manufacture.Methods: On the basis of Calverley's synthetic routes, we have studied thoroughly and in-depth about the pivotal steps of oxidization of the allyl-position, ozonization of the double bond in the side chain, Wittig reaction, stereoselective reduction of the carbonyl in the conjugated carbonyl compound and photochemical free radical reaction and ultimately to make those steps proceed smoothly.Results: We have achieved the hydroxylation of la-position, minimized the degree of epimerization in theα-position of aldehyde group and achieved the Wittig reaction smoothly by optimizing these reaction conditions. At the same time, the yield of each step up to or surpasses the record in the literature. We have proved that the target products were identical with the literature reported by characterizing each key intermediate through ¹H NMR, ¹³C NMR spectra.Conclusion: Through optimizing the reaction conditions, we have obtained the target compound-Calcipotriol in twelve steps starting from Vitamin D₂.