Design and synthesis of antiviral pseudo-natural products through effective one-step acylmethylation macrocyclization

Influenza virus poses a significant threat to global public health,causing serious repercussions on human life and social well-being.Over the past decades,various antiviral drugs targeting either the virus itself or its host were identified.However,the emergence of drug-resistant influenza virus strains has posed a critical challenge to the effectiveness of these existing anti-influenza agents .Consequently,there is an urgent need to develop novel molecules with new chemical frameworks.Macrocyclic natural products serve as a crucial resource for validating targets and discovering lead compounds.However,the number of naturlly crring macrocyclic natural products is limited due to inherent biosynthetic pathways,which restricts the development of macrocyclic drugs.In contrast,artificially synthesized pseudonatural products show enhanced availability and greater structural diversity,while possessing similar biological functions[5]and have attracted significant interest from medicinal chemists.Hence,it is valuable to develop effective synthetic methods to expedite the discovery of macrocyclic lead compounds.