Total Synthesis Of Entecavir For Anti-hepatitis B Virus

Entecavir is a first-line drug to anti-chronic hepatitis B virus,which is widely used in clinic because of its good curative effect,low drug resistance and small side effects.The structure of entecavir is composed of a five-membered ring and a guanine structure.Since the US pharmaceutical company Bristol-Myers Squibb first reported its fully synthetic route,several research groups have reported their synthetic work,however,the price of entecavir is still high.In this full text,entecavir was considered as the research target,and two synthetic routes to the key five-membered cyclic intermediate of entecavir were explored.Herein,the formal synthesis of entecavir was completed.The full text is divided into the following four chapters:The first chapter summarizes the hepatitis B virus and total synthesis.Simultaneously it briefly analyzes the significance of this article and introduces the domestic and foreign research status.The second chapter further expounds the research work on the synthesis of five-membered ring intermediate of entecavir,and elaborates two formal synthesis routes of entecavir: starting from the retroaynthetic analysis to analyze the design ideas,and detailedly explaining the synthesis route of five-membered ring intermediate.The first synthetic route involves Evans Aldol reaction,epoxidation reaction,and free radical reaction,etc;The second synthetic route involves Morita-Baylis-Hillman reaction,Sharpless Asymmetric epoxidation,epoxy opening,and Riley oxidation,etc.The corresponding reaction conditions have been optimized and screened.The third chapter shows the specific experimental steps,including the specific experimental operations,conditions,reaction phenomena appearing in each reaction,as well as the yield of each step reaction and the spectral analysis of related products.In the last chapter,the full text was summarized.