Click chemistry inspired facile one-pot synthesis of mannosyl triazoles and their hemagglutination inhibitory properties: The effect of alkyl chain spacer length between the triazole and phthalimide moieties in the aglycone backbone

Abstract

An efficient one-pot synthesis of a new series of mannosyl triazoles has been achieved through CuAAC reaction where the alkyl chain spacer between the phthalimide moiety and the triazole ring in the aglycone backbone is varied from one methylene to six methylene units. The target compounds were evaluated in terms of their inhibitory potency against FimH using hemagglutination inhibition (HAI) assay. It was found that the length of four methylene units was the optimum for the fitting/binding of the compound to FimH as exemplified by compound 11 (HAI = 1.9 μM), which was approximately 200 times more potent than the reference ligand 1(HAI = 385 μM). The successful implementation of one-pot protocol with building blocks 1-7 and the architecture of ligand 11 will be the subject of our future work for developing more potent FimH inhibitors.

Keywords: Carbohydrate; CuAAC reaction; FimH; Glycoconjugates; Phthalimide.