RESUMO
Previously, a method for the stereoselective synthesis of beta-lactams, starting from 2H-Delta(2)-thiazolines and Meldrum's acid derivatives, has been reported from our laboratory. We now report a new method for the synthesis of optically active, highly substituted ring-fused 2-pyridinones. This was discovered when 2-alkyl-Delta(2)-thiazolines and Meldrum's acid derivatives were treated with HCl(g) in benzene at 5 --> 78 degrees C. Further refinement of the synthetic protocol revealed that use of 1,2-dichloroethane as solvent at 0 --> 64 degrees C led to the desired 2-pyridinones in good yields and with excellent enantioselectivity. Use of these conditions allowed preparation of 2-pyridinones from several different Delta(2)-thiazolines and Meldrum's acid derivatives and may be a general route to 2-pyridinones.
Assuntos
Piridonas/síntese química , Antibacterianos/síntese química , Lactamas/síntese química , Hidrocarbonetos Policíclicos Aromáticos/síntese química , EstereoisomerismoAssuntos
Antibacterianos/química , Proteínas de Escherichia coli , Escherichia coli/efeitos dos fármacos , Proteínas de Fímbrias , Fímbrias Bacterianas/efeitos dos fármacos , Peptídeos/química , Proteínas Periplásmicas , Aminoácidos/síntese química , Aminoácidos/farmacologia , Antibacterianos/farmacologia , Proteínas da Membrana Bacteriana Externa/química , Proteínas de Bactérias/química , Desenho de Fármacos , Modelos Moleculares , Chaperonas Moleculares/química , Peptídeos/síntese química , Peptídeos/farmacologia , Piridonas/síntese química , Piridonas/farmacologia , Ressonância de Plasmônio de SuperfícieRESUMO
[reaction: see text] Optically active beta-lactams 3 are obtained in excellent yields (up to 93%) and with complete stereoselectivity from Meldrum's acid derivatives 1 and Delta(2)-thiazolines 2. A selective reduction to aldehydes 5 (R = Ar or CH(2)Ar) was then accomplished by using DIBAL-H. This rigid framework, with stereochemistry different than that of penicillin, is designed to be a suitable scaffold for the development of compounds inhibiting pilus formation in uropathogenic Escherichia coli.
