title: The synthesis of a series of deoxygenated 2,3-difluoro-N-acteylneuraminic acid derivatives as potential sialidase inhibitors.
abstract: 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.
authors.affiliation: Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, United Kingdom.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hader
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Watts
mesh_terms: D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010100:Oxygen / Q000737:chemistry*; D012794:Sialic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D012794:Sialic Acids; D009439:Neuraminidase; D010100:Oxygen