Glyco- and peptidomimetics from three-component Joullié-Ugi coupling show selective antiviral activity.

Timothy M Chapman, Ieuan G Davies, Baohua Gu, Timothy M Block, David I C Scopes, Philip A Hay, Stephen M Courtney, Luke A McNeill, Christopher J Schofield, Benjamin G Davis

Index: J. Am. Chem. Soc. 127(2) , 506-7, (2005)

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Abstract

Chlorination-elimination chemistry coupled with three-component Joullié-Ugi reaction and facile deprotection allowed efficient access to an array of polyhydroxylated pyrrolidines through parallel synthesis that may be considered to be a library of imino (aza) sugars (glycomimetics) and/or dihydroxyprolyl peptides (peptidomimetics). The utility of generating such a library was illustrated by screening against 15 different targets that revealed potent and selective inhibition of the Gaucher's disease glycosyltransferase enzyme glucosylceramide synthase and of primary pathogen model for human hepatitis C virus (HCV) and bovine diarrhoeal virus (BVDV). An observed selectivity for this HCV model over hepatitis B virus and remarkably low toxicity suggest a novel mode of action.