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Pure Appl. Chem., 2013, Vol. 85, No. 9, pp. 1803-1811

Published online 2013-08-09

Sialylexoenitols as precursors for new analogues of sialidase inhibitors

Barbara Richichi1, Carlotta Lunghi1, Athanasios Papakyriakou2, Oscar Francesconi1 and Cristina Nativi3,1*

1 Dipartimento di Chimica “Ugo Schiff”, Universita’ degli Studi di Firenze, via della Lastruccia, 13 50019 Sesto Florentino (FI), Italy
2 Chemical Biology and Designed Molecules Laboratory, NCSR “Demokritos”, 15310 Ag. Paraskevi, Athens, Greece
3 CNR, Istituto di Metodologie Chimiche IMC, Area di Ricerca di Roma 1, via Salaria Km 29, 300‑00015 Monterotondo, Roma, Italy

Abstract: Sialic acids are involved in a plethora of important biological events; among these the most known certainly is the binding of N-acetylneuraminic acid (Neu5Ac) with influenza virus sialidase. Considering Neu5Ac as the template that led to the structure-based development of the two potent antiviral agents zanamivir and oseltamivir, we developed the synthesis of the sialylexoenitol, a new class of sialyl derivative that was used as precursor in powerful hetero-Diels–Alder reactions to form the corresponding spiroketals. Docking calculations employing the crystallographic structure of influenza virus sialidase indicate that these scaffolds could probably interact with most of the active site residues that stabilize Neu5Ac. In addition, their reduced polar nature with respect to Neu5Ac derivatives might provide inhibitors with increased bioavailability.