Study On The Synthetic Process Of Fosamprenavir Calcium

AIDS(Acquired immunodeficiency syndrome)is a sort of communicable disease caused by HIV(Human immunodeficiency virus).The main therapeutic drugs can be classified to three categories: protease inhibitor,nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors.Fosamprenavir Calcium is one of the typical and quite effective protease inhibitor,which is also a protease inhibitor,coupled with convenient dose.Hence,Fosamprenavir Calcium has great prospects for development.According to the references,the classification of anti-AIDS drugs and the synthesis of protease inhibitors were reviewed in this paper.The synthesis and process optimization were discussed in the typical protease inhibitors of Fosamprenavir Calcium.N-((2R,3S)-3-amino-2-hydroxy-4-phenylbutyl)-N-isobutyl-4-nitrobenzenesulfonamide trifluoroacetate was used as starting material.The title product could be finally obtained by four steps: condensation,phosphine acylation,hydrogenation reduction and salt formation.A better synthesis process was obtained by optimizing reactant proportion,reaction temperature,solvents,reaction times,work up progress,etc.The structure of intermediate and the target compound were confirmed by NMR,MS.The total yield is up to 55.6 % with purification of 99.89 %(HPLC).This optimum synthetic route has many advantages,such as easy operation,avalible reagent,mild reaction condition,convenient separation and suitable for industrial production.