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Chemistry
. 2025 Jan 16:e202404342.
doi: 10.1002/chem.202404342. Online ahead of print. A Simple and Efficient Stereoselective Synthesis of a 2,3-Difluorosialic acid-based influenza virus neuraminidase inhibitor
Ibrahim El-Deeb 1 , Mark von Itzstein 1
Affiliations
3-Fluoroneuraminosyl fluorides are invaluable probes for studying the catalytic mechanism of sialidases (neuraminidases), and as sialidase inhibitors. Significantly, when a C-3 equatorial fluorine is installed on a C-4 functionalised N-acylneuraminic acid (Neu)-based template, the compounds are potent and selective inhibitors of both influenza and parainfluenza sialidases, and of virus replication. Typically, the reported syntheses of 3-fluoroneuraminosyl fluorides involve either an enzymatic or a chemical synthesis that have uncontrolled stereoselectivity in the introduction of fluorine at C-3 of Neu and consequently yield a mixture of C-3 ax and C-3 eq fluoro derivatives. We now report a simple approach for the exquisitely stereo-controlled introduction of the C-3 equatorial fluorine on Neu by incorporation of steric bulk at C-4. Through this method, we have elaborated a novel synthetic route that exclusively produces the potent anti-influenza drug candidate; 2,3-difluoro-zanamivir analogue with C-3 eq fluoride.
Keywords: Stereoselective, Sialidase, Sialic acid, Influenza virus, inhibitor.
. 2025 Jan 16:e202404342.
doi: 10.1002/chem.202404342. Online ahead of print. A Simple and Efficient Stereoselective Synthesis of a 2,3-Difluorosialic acid-based influenza virus neuraminidase inhibitor
Ibrahim El-Deeb 1 , Mark von Itzstein 1
Affiliations
- PMID: 39817632
- DOI: 10.1002/chem.202404342
3-Fluoroneuraminosyl fluorides are invaluable probes for studying the catalytic mechanism of sialidases (neuraminidases), and as sialidase inhibitors. Significantly, when a C-3 equatorial fluorine is installed on a C-4 functionalised N-acylneuraminic acid (Neu)-based template, the compounds are potent and selective inhibitors of both influenza and parainfluenza sialidases, and of virus replication. Typically, the reported syntheses of 3-fluoroneuraminosyl fluorides involve either an enzymatic or a chemical synthesis that have uncontrolled stereoselectivity in the introduction of fluorine at C-3 of Neu and consequently yield a mixture of C-3 ax and C-3 eq fluoro derivatives. We now report a simple approach for the exquisitely stereo-controlled introduction of the C-3 equatorial fluorine on Neu by incorporation of steric bulk at C-4. Through this method, we have elaborated a novel synthetic route that exclusively produces the potent anti-influenza drug candidate; 2,3-difluoro-zanamivir analogue with C-3 eq fluoride.
Keywords: Stereoselective, Sialidase, Sialic acid, Influenza virus, inhibitor.