A set of three mannopyranoside possessing identical 1,1'-biphenyl glycosidic pharmacophore but different aglyconic atoms were synthesized using either a palladium-catalyzed Heck cross coupling reaction or a metathesis reaction between their corresponding allylic glycoside derivatives. Their X-ray structures, together with their calculated 3D structures, showed strong indicators to explain the observed relative binding abilities against E. coli FimH as measured by a improved surface plasmon resonance (SPR) method. Amongst the O-, C-, and S-linked analogs, the C-linked analog showed the best ability to become a lead candidate as antagonist against uropathogenic E. coli with a Kd of 11.45 nM.
Keywords: D-mannosides; E. coli; FimH; Heck reaction; SPR; X-ray; carbohydrate; lectin; metathesis; uropathogenic infections.