Synthesis Of Nucleosides Of Anti-Tumor Agent GT And Anti-MDS Agent DT

The first part of this dissertation is the study on the synthesis of anti-tumor agent GT(Gemcitabine).GT was developed by Lilly company and listed in South Africa , Sweden , Netherlands and Australia in 1995 for clinical treatment of non-small cell lung cancer and pancreatic cancer. Its'hydrochloride is a new synthetic difluoronucleoside antineoplastic drug.The preparation of GT hydrochloride consisted of a nine-step process based on acetonation , oxidation , addition , cyclization ,benzo —ylation and reduction followed by mesylation , coupling , deprotection starting from D-mannitol as an industrialization synthetic route .The best temperature for the Reformatsky reaction and the optimum condition for the mesylation reaction to build β-nucleoside were found in the research. At the same time ,new approach was raised for the reaction ofacetonation and oxidation------the total yield was elevated from 36.1% to45% when the products of acetonation were used in oxidation without purification. Besides, the reactions of addition , cyclization and benzoylation were handled successively to adapted to the requirements of industrial production while making no effect to the yield.The second part of this dissertation is the study on the synthesis of anti-MDS agent DT(Decitabine), an analog of 2'-deoxycytidine marketed in America in 2006 .It was exploited by SuperGen company for the clinical treatment of myelodysplastic syndrome(MDS) and sickle-cell anemia (CML).DT was gained after acetylation , coupling and deprotection with 2-deoxy-D-ribose as a starting material. The method to deal with the residual acetic anhydride was improved by adjusting pH value in the reaction of acetylation. And nucleoside reaction was completed by catalyzing with Lewis acid ,skipping the Chlorinated reaction .