Synthesis Of An Active Vitamin D Drug Maxacalcitol

1α,25-dihydroxyvitamin D has known as active-form Vitamin D is a physiological action, and plays an essential role in the regulation of calcium and phosphate homeostasis and bone metabolism. Also it can express its biological activity by the transcription control of its cellular vitamin D receptor(VDR). Meanwhile, it was found that vitamin D receptor(VDR) distributed in a variety of cell types and tissues which indicate its non-classic function, include regulation of cell proliferation and differentiation, immunomodulatory and regulate the production and secretion of other hormones. These non-classic roles of potential therapeutic have effects on, such as autoimmune diseases, cardiovascular diseases, cancer, endocrine and metabolic diseases. However, due to the expression of the biological activity, the active vitamin D can elevate blood calcium concentration, initiator hypercalcemia psychosis, thus limiting the wide range of application. Therefore, to separate the calcemic properties of la,25(OH)D from its cell-differentiating properties to develop vitamin D analogs with specialized calcemic or noncalcemic use becomes the focus of the current study.Maxacalcitol(OTC), which contains an oxygen in place of carbon22of the side chain, was develop-ped by Chugai in Japan in2000for the first time in practice, the injection is mainly used treatment for secondary hyperparathyroidism(SHPT), and the ointment for treatment of psoriasis, it is weaker in inhib-iting parathyroid hormone(PTH) and regulating calcium level compared with calcitriol, so, long-term medication does not cause hypercalcemia.Psoriasis is a common chronic inflammatory disease that is easy to recur. In China, the prevalence rate is about0.05%to0.08%, and the variety of domestic active vitamin D analo-gues drugs used to treat Psoriasis is few. Chronic kidney disease(CDK), the high cardiovas-cular disease incidence and mortality make the patients’life become shorter than expect, which can also lead to lack of active vitamin D3in the dialysis process, and cause secondary hyperparathyroidism, which increases much more suffering of patients. For this, it has great significance to. develop a new maxacalcitol synthetic route for the citizen and patients themselves.In this paper, a new route of synthesis maxacalcitol based on reported in the literature. DHEA is raw material, the first protected by TBS, Wittig reaction, borohydride-oxidation, Williamson reaction, brominated-debromination to get the B ring intermediate of conjugated diene, then photochemical and isomerization after de-TBS protection, at last, subjected to biotransformation which gives maxacalcitol.The new route of synthetic maxacalcitol is not only with a high yield, mild conditions, easy to operate but also made a foundation for factory production, more importantly, giving a backword for the subsequent production of active vitamin D analogs.