New aminothiazolylglycylcephalosporins with a 1,5-dihydroxy-4-pyridone-2-carbonyl group. II. Synthesis and antibacterial activity of MT0703 and its diastereomers.
A practical synthetic method for large scale production of MT0703, (6R,7R)-7-[(RS)-2-(2-aminothiazol-4-yl)-2-(1,5-dihydroxy-4-pyridon e-2- carboxamido)acetamido]-3-[[1-(2-hydroxyethyl)pyridinium-4- yl]thiomethyl]ceph-3-em-4-carboxylate, was established. Its two diastereomers on configuration of the aminothiazolylglycyl moiety were synthesized using chemico-enzymatic method. The S-isomer of MT0703 was found to be more active against Gram-positive and Gram-negative bacteria including beta-lactamase-producing strains than the R-isomer.
Ogino
H
H
Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., Yokohama, Japan.
Iwamatsu
K
K
Katano
K
K
Nakabayashi
S
S
Yoshida
T
T
Shibahara
S
S
Tsuruoka
T
T
Inouye
S
S
Kondo
S
S
D000818:Animals; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D004927:Escherichia coli Infections / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008826:Microbial Sensitivity Tests; D011552:Pseudomonas Infections / Q000188:drug therapy; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D002511:Cephalosporins; C063437:MT 0703