RESUMO
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).
Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Éteres/química , Éteres/farmacologia , Bactérias Gram-Positivas/efeitos dos fármacos , Anti-Infecciosos/síntese química , Farmacorresistência Bacteriana/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Polissorbatos/químicaRESUMO
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.
Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecium/efeitos dos fármacos , Glucosídeos/química , Listeria monocytogenes/efeitos dos fármacos , Éteres Metílicos/química , Staphylococcus aureus/efeitos dos fármacos , Daptomicina/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Enterococcus faecalis/crescimento & desenvolvimento , Enterococcus faecium/crescimento & desenvolvimento , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Listeria monocytogenes/crescimento & desenvolvimento , Listeriose/tratamento farmacológico , Listeriose/microbiologia , Meticilina/farmacologia , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/crescimento & desenvolvimento , Vancomicina/farmacologiaRESUMO
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 ).
Assuntos
Benzofuranos/síntese química , Furanos/síntese química , Benzofuranos/química , Catálise , Furanos/química , EstereoisomerismoRESUMO
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.
Assuntos
Alcenos/química , Bases de Lewis/química , Pirrolidinas/síntese química , Tetramizol/química , Alquilação , Estrutura Molecular , Pirrolidinas/química , EstereoisomerismoRESUMO
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).
Assuntos
Ácidos Carboxílicos/química , Pironas/síntese química , Tioureia/análogos & derivados , Tioureia/química , Catálise , Ciclização , Estrutura Molecular , Pironas/química , EstereoisomerismoRESUMO
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.