Selectfluor and NFSI exo‐Glycal Fluorination Strategies Applied to the Enhancement of the Binding Affinity of Galactofuranosyltransferase GlfT2 Inhibitors. Issue 46 (24th September 2014)

• Record Type: Journal Article
• Authors: Dumitrescu, Lidia; Eppe, Guillaume; Tikad, Abdellatif; Pan, Weidong; Bkassiny, Sandy El; Gurcha, Sudagar S.; Ardá, Ana; Jiménez‐Barbero, Jesús; Besra, Gurdyal S.; Vincent, Stéphane P.
• Is Part Of: Chemistry. Volume 20:Issue 46(2014)
• Page Start: 15208
• Page End: 15215
• Publication Date: 2014-09-24
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201404180
• Languages: English
• ISSNs: 0947-6539

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Two complementary methods for the synthesis of fluorinated <italic>exo</italic>‐glycals have been developed, for which previously no general reaction had been available. First, a Selectfluor‐mediated fluorination was optimized after detailed analysis of all the reaction parameters. A dramatic effect of molecular sieves on the course of the reaction was observed. The reaction was generalized with a set of biologically relevant furanosides and pyranosides. A second direct approach involving carbanionic chemistry and the use of <italic>N</italic>‐fluorobenzenesulfonimide (NFSI) was performed and this method gave better diastereoselectivities. Assignment of the <italic>Z</italic>/<italic>E</italic> configuration of all the fluorinated <italic>exo</italic>‐glycals was achieved based on the results of HOESY experiments. Furthermore, fluorinated <italic>exo</italic>‐glycal analogues of UDP‐galactofuranose were prepared and assayed against Gl<italic>f</italic>T2, which is a key enzyme involved in the cell‐wall biosynthesis of major pathogens. The fluorinated <italic>exo</italic>‐glycals proved to be potent inhibitors as compared with a series of <italic>C</italic>‐glycosidic analogues of UDP‐Gal<italic>f</italic>, thus demonstrating the double beneficial effect of the exocyclic enol ether functionality and the fluorine atom.</p> </abstract>