This proposal describes a new route to isoxazole-based scaffolds as inhibitors of the influenza neuraminidase enzyme. The isoxazole that was prepared possesses the main functional groups that are needed for binding to the Neuraminidase Enzyme of the Influenza Virus. These interactions were identified in the crystal structure of the known laninamivir–NA complex. These Isoxazoles were created from a 1,3-dipolar cycloaddition reaction of an oxime and an alkyne. The general scheme of this route includes the following: (1) The synthesis of 2-(chloro(hydroxyimino)methyl)pyrrolidone-1-carboxylate, a chloro-oxime. (2) The preparation of 4-Ethynyl-2,2-dimethyl-1,3-dioxolane from 1,2:5,6-Di-O-isopropylidene-D-mannitol, the alkyne and (3) the coupling of -(chloro(hydroxyimino)methyl)pyrrolidone-1-carboxylate and 4-Ethynyl-2,2-dimethyl-1,3-dioxolane to form the product. These products still need to be tested for their potency against the influenza neuraminidase inhibitors. This project will effectively prepare isoxazole analogs as mimetics of the drug, laninamivir in an efficient way.

Isoxazole-based inhibitors of the neuraminidase enzyme of the influenza virus

253rd National Meeting (2017)

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