Ferrocene conjugates with mannose: synthesis and influence of ferrocene aglycon on mannose‐mediated adhesion of Escherichia coli

Bacterial adhesion, mediated through interaction of bacterial lectins with carbohydrate structures presented on the surface of the host cells, is a prerequisite for infection. Anti‐adhesion therapy, based on the inhibition of lectins by suitable carbohydrates, has been considered as a weapon for the combat of microbial diseases. Structural alteration of aglycon portions of mannose derivatives strongly influences their inhibitory potency toward type 1 fimbriated Escherichia coli. Thus several conjugates of mannose‐containing ferrocene aglycon moieties were synthesized and tested. The novel ferrocene conjugates 10, 12 and 14 were obtained by esterification of O‐mannosylated propionic acid 1 with ferrocene alcohols R‐Fn‐(CH₂)_n‐OH (Fn = 1,1'‐ferrocenylene; 2, n = 1, R = COOMe; 7, n = 1, R = NHBoc; 8, n = 2, R = H) in the presence of Boc₂O/DMAP with subsequent debenzylation of the intermediate O‐protected esters. Performed hemagglutination inhibitory tests showed that the examined bioorganometallics exhibit better inhibitory activity than known inhibitor methyl α‐d ‐mannoside. Thus ferrocene–mannose conjugate 14 with the dimethylene spacer between ferrocene core and chiral linker displayed the best inhibitory efficiency. Copyright © 2012 John Wiley & Sons, Ltd.