Preparation and antibiotic activity of monobactam analogues of nocardicins.
A series of diverse beta-lactam analogues of nocardicins with interesting antimicrobial properties were prepared. Coupling of glucosamine to these compounds improved their water solubility. Aminoacid derivatives produced a stereoinduction on the quaternary enantiotopic carbon of the starting compound 1. Evaluation of their antimicrobial activity showed that the introduction of alpha-amninoacids to monobactams increased their activity. The importance of asymmetric carbon is exemplified by the higher antibiotic activity of L-alpha-aminoacids than the D-series. No significant difference was observed between fluorinated and non-fluorinated monobactams.
Gerardin-Charbonnier
C
C
Université Henri Poincaré-Nancy I, Laboratoire de Chimie Physique Organique et Colloïdale, LCPOC UMR CNRS-UHP 7565, Nancy Vandoeuvre, France.
Auberger
S
S
Molina
L
L
Achilefu
S
S
Manresa
M A
MA
Vinardell
P
P
Infante
M R
MR
Selve
C
C
D000667:Ampicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D007536:Isomerism; D007769:Lactams; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D008956:Models, Chemical; D008997:Monobactams / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010406:Penicillins / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D007769:Lactams; D008997:Monobactams; D010406:Penicillins; C027318:nocardicin; D000667:Ampicillin