C-2 위치에 5'-Ethoxycarbonylmethoxy(hydroxy)iminopyrrolidinylthio Group을 가진 1β-Methylcarbapenems의 합성과 생물학적 성질

Synthesis and Biological Properties of 1β-Methylcarbapenems with 5'-Ethoxycarbonylmethoxy(hydroxy)iminopyrrolidinylthio Group at C-2 Position

Synthesis of (1R,5S,6S)-6-[(1R-1-hydroxyethyl]-2- [(3S,5S)-5-(2-ethoxycarbonyl-1-moxy(hydroxy)iminoethyl)pyrrolidine-3- ylthio]-1-methylcarbapen-2-em-3-carboxylic acids (10a,10b) were described. Methyl(2S,4S)-4-tritylthio-1-(allyloxycarbonyl)pyrrolidine-2-carboxyla late (1) was prepared from trans-4-hydroxy-L-proline with (2S,4R)-abs olute configuration as starting material. (2S,4S)-1-allyloxycarbonyl-2-(2-ethoxycarbonyl- hydroxy(methoxy)iminoethyl)-4-mercapto- pyrrolidines (6,7) were obtained from the tritylthio compound (1). (1R,5S,6S)-6-[(1R)-1- hydroxyethyl]-2-[(3S,5S)-5-(2-ethoxycarbonyl-1-methoxy(hydroxy)imino- ethyl)pyrrolidine-3-ylthio]-1-methylcarbapem-2-em-3-carboxylic acids (10a, 10b) were obtained by the coupling reaction with carbapenem diphenylphosphates (8) and pyrrolidine-thiol moiety (6,7). Their in vitro antibacterial activities against both Gram-positive and Gram-negative were tested. Compounds (10a,10b) showed potent antibacterial activity except pseudomonas aerusinosa.