RESUMO
A series of 1beta-methylcarbapenems bearing an (imidazo[5,1-b]thiazolium-6-yl)methyl moiety, a 5,5-fused heterobicycle, at the C-2 position was synthesized and evaluated for in vitro antibacterial activities. CP0569 (1r) and its analogues showed potent antibacterial activities against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), and Gram-negative bacteria, including Pseudomonas aeruginosa. Moreover, CP0569 (1r) exhibited stronger antibacterial activity against MRSA and higher resistance to renal dehydropeptidase-1 (DHP-1) than any currently marketed carbapenems, that is, imipenem (IPM), panipenem (PAPM), and meropenem (MEPM).
Assuntos
Carbapenêmicos/síntese química , Carbapenêmicos/farmacologia , Animais , Carbapenêmicos/química , Dipeptidases/metabolismo , Farmacorresistência Bacteriana , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/enzimologia , Rim/metabolismo , Lactamas/síntese química , Lactamas/química , Lactamas/farmacologia , Resistência a Meticilina , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , SuínosRESUMO
[Ni(cyclam)](ClO(4))(2)-catalyzed indirect electroreduction of olefinic bromides produced six-membered compounds in low to high yields. The synthetic intermediate 49 of Ipecac and Corynanthe alkaloids was obtained in 88% yield in a highly stereoselective manner. Lactam 66, the synthetic precursor of tacamonine, was prepared in 49% yield as a mixture of two diastereoisomers. The electrolysis of the bromoacetates gave the debrominated compounds in good yields.
