ABSTRACT
A range of amphiphilic sorbitan ethers has been synthesized in two steps from sorbitan following an acetalization/hydrogenolysis sequence. These sorbitan ethers and the acetal intermediates have been evaluated as antimicrobials against Gram-negative and Gram-positive bacteria. No antimicrobial activity was observed for Gram-negative bacteria. However, the compounds bearing a linear dodecyl chain exhibit antimicrobial activity (MIC as low as 8µg/mL) against Gram-positive bacteria such as Listeria monocytogenes, Enterococcus faecalis and Staphylococcus aureus. Encouraged by these preliminary results, dodecyl sorbitan was tested against a range of resistant strains and was found to be active against vancomycin-, methicillin- and daptomycin-resistant strains (MIC=32-64µg/mL).
Subject(s)
Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Ethers/chemistry , Ethers/pharmacology , Gram-Positive Bacteria/drug effects , Anti-Infective Agents/chemical synthesis , Drug Resistance, Bacterial/drug effects , Microbial Sensitivity Tests , Polysorbates/chemistryABSTRACT
A series of amphiphilic methyl glucopyranoside ethers incorporating various alkyl chain lengths has been synthesized from commercially available methyl glucopyranosides following an acetalisation/hydrogenolysis sequence. The amphiphilic properties of ethers and acetal intermediates were evaluated. Both families exhibit excellent surfactant properties with a maximum efficiency obtained for compounds bearing a linear dodecyl chain (CMC = 0.012 mM, γsat. = 30 mN m-1). Antimicrobial activity studies revealed an efficient activity (0.03 < MIC < 0.12 mM) against Gram-positive bacteria such as Listeria monocytogenes, Enterococcus faecalis, Enterococcus faecium and Staphylococcus aureus. More importantly, these compounds were found to be active against multi-resistant strains such as vancomycin-, methicillin- and daptomycin-resistant strains. Finally, it was found that antimicrobial activities are closely related to physicochemical properties and are also influenced by the nature of the carbohydrate moiety.
Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Enterococcus faecalis/drug effects , Enterococcus faecium/drug effects , Glucosides/chemistry , Listeria monocytogenes/drug effects , Methyl Ethers/chemistry , Staphylococcus aureus/drug effects , Daptomycin/pharmacology , Drug Resistance, Multiple/drug effects , Enterococcus faecalis/growth & development , Enterococcus faecium/growth & development , Gram-Positive Bacterial Infections/drug therapy , Gram-Positive Bacterial Infections/microbiology , Humans , Listeria monocytogenes/growth & development , Listeriosis/drug therapy , Listeriosis/microbiology , Methicillin/pharmacology , Microbial Sensitivity Tests , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Staphylococcus aureus/growth & development , Vancomycin/pharmacologyABSTRACT
A general, transition-metal-free, highly stereoselective cross-coupling reaction between glycosyl bromides and various arylzinc reagents leading to ß-arylated glycosides is reported. The stereoselectivity of the reaction is explained by invoking anchimeric assistance via a bicyclic intermediate. Stereochemical probes confirm the participation of the 2-pivaloyloxy group. Finally, this new method was applied to a short and efficient stereoselective synthesis of Dapagliflozin and Canagliflozin.
