Study On Synthesis Of Zidovudine With Thymidine

5-methyluridine,nucloside anti-AIDS drug intermediate,is widely used for the synthesis of many nucleoside anti-AIDS drugs,such as zidovudine,stavudine,alovudine,fozivudine,telbivudine,etc.This thesis summarized the application progress of 5-methyluridine,and focused on the research progress of zidovudine.The optimum process conditions of zidovudine based on 5-methyluridine as raw material were further achieved.The route had many advantages of high economical efficiency,few reaction steps,high yield and good environment friendliness.Because of relatively high synthesis cost of 5-methyluridine,this route was not well optimized.However,the synthesis way of 5-methyluridine has been optimized in recent years and the price of raw material constantly dropped,which enables 5-methyluridine to become a very competitive raw material for the synthesis of zidovudine.The molar yield further exceeds 90%.5-methyluridine as raw material was treated by dehydration,bromination,debromination and hydrogenation to produce β-thymidine with a molar yield of 91.3%.β-thymidine was further processed through dehydration,protection of group,azidation,hydrolysis de-protection of group and crystallization to obtain the product of zidovudine with a molar yield of 91.2%.The optimized route for the synthesis of zidovudine has the advantages of short process route,easily accessible raw material,mild reaction conditions and high overall yield of 83.3%.The key point of optimization is the choice of economical sodium azide as reagent,chemically stable acetyl as the protection group on the glycosyl at a temperature of 100 C,the mixture solution with DMF and water as the solvent.The above process completely meets the requirements of production and can attain good economic benefit.