RESUMO
We report the diastereoselective and chromatography-free syntheses of four 2-phenyl-6-alkyl-3-aminopiperidines. Ring construction was accomplished through a nitro-Mannich reaction linking a nitroketone and phenylmethanimine, followed by a ring-closure condensation. Relative stereocontrol was achieved between C-2 and C-3 by kinetic protonation of a nitronate or by equilibration of the nitro group under thermodynamic control. Stereocontrol at C-6 was accomplished by utilizing a variety of imine reduction methods. The C-2/C-6-cis stereochemistry was established via triacetoxyborohydride iminium ion reduction, whereas the trans relationship was set either by triethylsilane/TFA acyliminium ion reduction or by Lewis acid catalyzed imine reduction with lithium aluminum hydride.
Assuntos
Cetonas/química , Nitrocompostos/química , Piperidinas/síntese química , Derivados de Benzeno/síntese química , Cinética , EstereoisomerismoRESUMO
Aryl and hetero aryl substituted 3,6-ketals of 15-membered azalide analogues were synthesized and were found to have potent in vitro antibacterial activity against veterinary pathogens, including Staphylococcus aureus and Pasteurella multocida.
Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/farmacologia , Compostos Heterocíclicos/síntese química , Compostos Heterocíclicos/farmacologia , Animais , Bovinos , Doenças dos Bovinos/microbiologia , Feminino , Hormônio Liberador de Gonadotropina/síntese química , Mastite Bovina/microbiologia , Camundongos , Testes de Sensibilidade Microbiana , Pasteurella multocida/efeitos dos fármacos , Pasteurelose Pneumônica/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
3,6-Ketals of 15-membered azalide pseudoaglycones are a novel series of macrolide antibiotics. The aromatic derivatives of the azalide 3,6-ketals demonstrated potent antibacterial activities against both Gram-positive and Gram-negative bacteria.