Selectfluor and NFSI exo-glycal fluorination strategies applied to the enhancement of the binding affinity of galactofuranosyltransferase GlfT2 inhibitors.
Chemistry
; 20(46): 15208-15, 2014 Nov 10.
Article
em En
| MEDLINE
| ID: mdl-25251918
ABSTRACT
Two complementary methods for the synthesis of fluorinated exo-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 N-fluorobenzenesulfonimide (NFSI) was performed and this method gave better diastereoselectivities. Assignment of the Z/E configuration of all the fluorinated exo-glycals was achieved based on the results of HOESY experiments. Furthermore, fluorinated exo-glycal analogues of UDP-galactofuranose were prepared and assayed against GlfT2, which is a key enzyme involved in the cell-wall biosynthesis of major pathogens. The fluorinated exo-glycals proved to be potent inhibitors as compared with a series of C-glycosidic analogues of UDP-Galf, thus demonstrating the double beneficial effect of the exocyclic enol ether functionality and the fluorine atom.
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Base de dados:
MEDLINE
Assunto principal:
Sulfonamidas
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Difosfato de Uridina
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Compostos de Diazônio
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Inibidores Enzimáticos
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Galactose
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Galactosiltransferases
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article