The synthesis of a series of deoxygenated 2,3-difluoro-N-acteylneuraminic acid derivatives as potential sialidase inhibitors

• We have synthesised a series of mono-deoxygenated difluorosialic acids.
• We have applied Barton–McCombie deoxygenation conditions to difluorosialic acids.
• We have utilised the radical initiator Luperox for Barton–McCombie deoxygenations.

Here we describe the successful syntheses of a series of 4-, 7-, 8- and 9-deoxygenated 2,3-difluoro-N-acetylneuraminic acid derivatives as potential mechanism-based inhibitors of sialidases. The syntheses commenced utilising an enzyme-catalysed aldolase reaction between N-acetyl mannosamine and β-fluoropyruvic acid to give 3-fluoro-N-acetyl-neuraminic acid. This common intermediate was then used in selective protection protocols and Barton–McCombie deoxygenations to generate the complete set of mono-deoxygenated 3-fluoro-N-acetylneuraminic acid derivatives. Finally, a fluorination step utilising (diethylamino)sulfur trifluoride (DAST) was used to successfully generate each of the target difluorides.

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