The Synthesis Of3'-O-TBDMS-5'-O-DMT Phosphoramidite

Nucleoside compounds show an irreplaceable role as drugs in the prevention of virus, tumor, which is expected to become the important drugs to human after sulfonamides and antibiotics.At present, there are three kinds of methods to synthesize nucleoside drugs:RNA enzymatic hydrolysis, enzymatic synthesis method, and chemical synthesis. There are many ways of Chemical synthesis method, however, because the glycosidic bond formation is lack of stereo specificity, and it is difficult to get raw materials; the reagent is expensive and has a certain toxicity, which makes the production cost is high, and the yield is very low.This thesis studied on nucleoside product2'-O-TBDMS-5'-O-DMT Phosphoramidite nucleoside monomers. In synthesis process of this material, there is a critical impurity3'-O-TBDMS-5'-O-DMT Phosphoramidite nucleoside monomer, this is a very important impurity on the quality of the product. According to the synthesis mechanism of2'-O-TBDMS-5'-O-DMT Phosphoramidite nucleoside monomer, firstly, we prepare the monomer intermediates, and then separate and extract a critical impurity3'-O-TBDMS-5'-O-DMT Phosphoramidite nucleoside monomer from intermediates, and further simulate the related reaction for preparation of3'-O-TBDMS-5'-O-DMT Phosphoramidite nucleoside monomer of the final product. Based on the research to the synthetic route of a series of intermediates and products, identifying the main reactive impurities structures, and obtaining the corresponding impurity reference, providing a strong critical support to the goal product's analysis research and development, quality standards study. Then, by studying the target product preparation route, with more optimized technology we can get the high yield, higher purity products, which make up the national drug standard requirements, and get the best economic benefit.