Tri- and hexavalent mannoside clusters as potential inhibitors of type 1 fimbriated bacteria using pentaerythritol and triazole linkages

Abstract

Several oligomannoside clusters having a hundred-fold increase in affinities toward E. coli were synthesized by Cu(I)-catalyzed [1,3]-dipolar cycloadditions using pentaerythritol scaffolds bearing either alkyne or azide functionalities.

Mannosylated G(0) Dendrimers with Nanomolar Affinities to Escherichia coli FimH

“…All attempts to prepare hexakispropargyl scaffold from bis-pentaerythritol or hexatosylated dipenta-A C H T U N G T R E N N U N G erythritol 15 [30] failed. The novel hexameric azide 19 [21] was obtained by conversion of hexatosylated dipentaerythritol derivative 15, which, under the above cycloaddition conditions afforded hexamer 21 after deacetylation (Scheme 5). The structural integrity of the carbohydrate-coated clusters (glycodendrimers of generation G0) has been fully proven by chromatographic and spectroscopic techniques, including NMR spectroscopy and mass spectrometry.…”

“…Toward this goal, single step multiple Sonogashira coupling [20] and click chemistry were used. [21] Preliminary data from this last family of compounds indicated that they were more potent inhibitors than monomeric d-mannose. [22] These results stimulated the synthesis of further pentaerythritol-based glycodendrimers having aromatic (aryl or triazole) aglycones.…”

Unique tetrameric and hexameric mannoside clusters prepared by click chemistry

“…23 In particular, those derived from mannose have been synthesized and investigated as inhibitors of bacterial adhesion by different research groups. [24][25][26][27][28][29][30][31][32][33][34][35][36][37] We aim to expand the repertoire of available polyvalent mannosides in order to determine which scaffolds are most compatible with the FimH environment. We have chosen to use linker arms matching the heptyl glycoside that binds well to FimH 10,12 as others have done with different scoffolds.…”

“…38 A number of mannose-tipped dendrimers have been prepared using this reaction at some stage of their synthesis. 24,25,28,30,31,35,37 Herein, we report the syntheses of unique tetrameric and hexameric mannoside clusters built on hydroquinone and 1,1,1-tris(4-hydroxyphenyl)ethane scaffolds by a convergent strategy using click chemistry.…”

Clickable Glycopeptoids for Synthesis of Glycopeptide Mimic

“…[22][23][24][25] Selective and systematic substitution of natural amide bonds with triazole rings in synthetic N-linked glycopeptoids will introduce not only structural diversity but also improve their proteolytic stability for bio-medical application. In this present work, a series of triazole linked αβ-hybrid glycopeptoids were synthesized with systematic variation of the peptoid and the glycan part ( Figure 2).…”