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 stereodivergent asymmetric Lewis base catalyzed Michael addition/lactonization of enone acids into substituted dihydrobenzofuran and tetrahydrofuran derivatives is reported. Commercially available (S)-(-)-tetramisole hydrochloride gives products with high syn diastereoselectivity in excellent enantioselectivity (up to 99:1 d.r.syn/anti , 99 % eesyn ), whereas using a cinchona alkaloid derived catalyst gives the corresponding anti-diastereoisomers as the major product (up to 10:90 d.r.syn/anti , 99 % eeanti ).
Subject(s)
Benzofurans/chemical synthesis , Furans/chemical synthesis , Benzofurans/chemistry , Catalysis , Furans/chemistry , StereoisomerismABSTRACT
Telescoped and one-pot olefination/asymmetric functionalization approaches to disubstituted pyrrolidines (dr up to 99:1, up to 99% ee) have been developed using commercially available tetramisole (0.1 to 5 mol %). Using OTMS-quinidine as the Lewis base gives preferential access to an anti-configured pyrrolidine in high enantioselectivity.
Subject(s)
Alkenes/chemistry , Lewis Bases/chemistry , Pyrrolidines/chemical synthesis , Tetramisole/chemistry , Alkylation , Molecular Structure , Pyrrolidines/chemistry , StereoisomerismABSTRACT
Tetramisole promotes the catalytic asymmetric intramolecular Michael addition-lactonization of a variety of enone acids, giving carbo- and heterocyclic products with high diastereo- and enantiocontrol (up to 99:1 dr, up to 99% ee) that are readily derivatized to afford functionalized indene and dihydrobenzofuran carboxylates. Chiral isothioureas also promote the catalytic asymmetric intermolecular Michael addition-lactonization of arylacetic acids and α-keto-ß,γ-unsaturated esters, giving anti-dihydropyranones with high diastereo- and enantiocontrol (up to 98:2 dr, up to 99% ee).
Subject(s)
Carboxylic Acids/chemistry , Pyrones/chemical synthesis , Thiourea/analogs & derivatives , Thiourea/chemistry , Catalysis , Cyclization , Molecular Structure , Pyrones/chemistry , StereoisomerismABSTRACT
The catalytic activity and enantioselectivity in the kinetic resolution of (±)-1-naphthylethanol with a range of structurally related 3,4-dihydropyrimido[2,1-b]benzothiazole-based catalysts is examined. Of the isothiourea catalysts screened, (2S,3R)-2-phenyl-3-isopropyl substitution proved optimal, giving good levels of selectivity in the kinetic resolution of a number of secondary alcohols (S values up to >100 at ~50% conversion). Low catalyst loadings (0.10-0.25 mol%) of the optimal isothiourea can be used to generate enantiopure alcohols (>99% ee) in good yields.
