ABSTRACT
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.
Subject(s)
Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Lactams , Monobactams/chemical synthesis , Monobactams/pharmacology , Ampicillin/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Candida albicans/drug effects , Chemistry, Pharmaceutical/methods , Isomerism , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Models, Chemical , Monobactams/chemistry , Penicillins/pharmacologyABSTRACT
The reaction of amines of sodium azide with 3-perfluoroalkyl-3-fluoroprop-2-enoate, followed by hydrogenation, affords perfluoroalkylated beta-alanine analogues in very good yields. These compounds can be linked via an amide bond to produce peptide analogues such as carnosine or carcinine derivatives, which could have surfactive and complexing properties.