Synthetic Study towards Entecavir

A synthetic design of Entecavir was described, and the intermediate, (S)-N-methoxy -3-((4-methoxybenzyl)oxy)-N-methylpent-4-enamide, was synthesized using acrylaldehyde as the starting material, which was obtained via an Evans Aldol reaction, Weinreb amide formation, and a PMB protection. Introduction Hepatitis B virus (HBV) represents one of the most prevalent viral diseases in the world and is known to be a cause of serious liver disorders. It is reported that more than 400 million people have been chronically infected and there is a continuing need for new therapies for individuals infected with HBV. Entecavir (BMS-200475, 1) (Fig. 1) is a carbocyclic guanosine nucleoside analog with potent selectivity against hepatitis B virus which was approved under the trade name Baraclude in March 2005 by the US Food and Drug Administration for the treatment of chronic HBV infection in adults. Entecavir inhibits DNA synthesis in HBV infected cells in three steps: the priming of the polymerase, the reverse transcription of the pregenomic messenger RNA and the synthesis of the positive strand of HBV DNA. Entecavir is also effected to lamivudineand adefovir-resistant HBV strains. Figure 1. The structure of Entecavir As Entecavir’s remarkable potency, resistance, and safety profile, a great deal of synthetic effort has been devoted to the enantiospecific syntheses of Entecavir, among which most reported syntheses employ five-membered carbocyclic compounds as the starting material. In our study, we would describe our synthetic analysis towards Entecavir using acrylaldehyde as the starting material to construct the protected five member ring Entecavir 1 and our present work of the synthesis towards Entecavir. Our retrosynthetic route is outlined in Scheme 2. International Conference on Advances in Energy, Environment and Chemical Engineering (AEECE-2015) © 2015. The authors Published by Atlantis Press 840