Synthesis Of Zanamivir Analogues From Sialic Acid And Their Structure-activity Relationship Study

The influenza A is an acute respiratory infection caused by the influenza A virus and still athreaten to human health.So developing new and effective drug against influenza virus is immediate.Influenza virus neuraminidase inhibitors(NAIs)is an important type of anti-influenza drug developed in recent years,based on rational drug design.Several neuraminidase inhibitors have been widely used in clinic practice such as zanamivir,oseltamivir,and peramivir.In this paper,we designed and synthesized zanamivir analogues,and studied their biological activity.This paper included the following parts:(1)Literature searching and synthetic route designing;(2)Through methyl esteration and S-glycosylation to protection the C-1 carboxylic acid and C-2 hemi-acetal,then selective protected C-8,C-9,and C-4 followed by oxidation and reduction of C-7 to inversion the configuration,then using ? elimination to construct unsaturated ring;(3)Modified C-7 site to acquire series of new compounds,all new compound were characeterizaed by NMR and MS;(4)The structure-activity relationship study by analysis the inhibition activity to some neuraminidase.The information of the strutrue and activity could provide more insight information for the further design and synthesis of anti-influenza virus drugs.The innovation of this paper is to use the interaction of neuraminidase and substrat to design of the new zanamivir analogues with C-7 inversed configuration.