Research On The New Chemical Synthesis Process Of Docalcidol

Vitamin D are a widely studied vitamin in the vitamin families.They are originally found by maintain calcium balance in our body.They can be used to treat rickets,osteoporosis,etc.In recent decades,researches have found that the VD receptors are resided in most organs throughout our body.It has focused more and more attention as the mechanism of action in the body is getting clearer,and the finding of other functions such as treatment of hyperphosphatemia,hyperparathyroidism,SHPT(S econdary Hyperparathyroidism),psoriasis,etc.There are many vitamin D derivatives launched in China currently,which could be devided into vitamin D2 and vitamin D3 derivatives,but only a few drugs get the functions among the above-mentioned.For the patients,it is urgently to add new products to enrich their choices.Doxercalciferol is an important derivative of VD2,mainly used for the treatment of SHPT,hyperphosphatemia in the patients with uremia,etc.Doxercalciferol is an important derivative of vitamin D2,which is mainly used for the treatment of secondary hyperparathyroidism and hyperphosphatemia in patients with uremia.Based on the synthesis of vitamin D and Doxercalciferol,drawing the experiences of vitamin D derivatives' synthesis,this paper explores a new route for the synthesis of Doxercalciferol and obtains a practical synthetic route suitable for industrial production,explored the synthesis of Paricalcitol at the same time.Through the research,this paper has achieved the following objectives:1.According to comparing and analyzing the currently reported literatures,a new chemical synthesis route of Doxercalciferol was designed and explored.2.Study the key step(oxidation reaction),adjust the reaction conditions,and increase the yield of key reaction step:30.2%to 49.1%.3.The silicon etherification reaction was adding to the key intermediate(the oxidation reaction product),and the crystallization conditions of silicon etherification were explored,and the impurities and isomers were effectively separated,so that the requirements for post-oxidation treatment were simplified,and the controlling of the route was improved.It is also the biggest improvement to the route.4.Cost reduction is significantly:the cost of the new route is about 3050-3200 RMB/g,which is at least 1,000 RMB/g lower than the current lowest one.5.The steps have been adjusted to make the process more suitable for industrial production;the final batch is over 1g,the specifications of the Doxercalciferol soft capsules are 0.5?g,1?g and 2.5?g,and the clinical batch is calculated as 300,000 tablets;The required batche scales are 1.2g,which means the scale could meet the clinical batch requirements.