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Theoretical Calculations of β‐Lactam Antibiotics. Part VI. AM1 calculations of alkaline hydrolysis of clavulanic acid
Author(s) -
Frau Juan,
Donoso Josefa,
Muñoz Francisco,
Blanco Francisco García
Publication year - 1994
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19940770611
Subject(s) - chemistry , oxazolidine , lactam , thiazolidine , clavulanic acid , ring (chemistry) , cephalosporin , hydrolysis , stereochemistry , alkaline hydrolysis , cleavage (geology) , streptomyces clavuligerus , antibiotics , organic chemistry , amoxicillin , biochemistry , geotechnical engineering , fracture (geology) , engineering
The gas‐phase basic hydrolysis of clavulanic acid ( a ) was studied by using the AM1 semi‐empirical method. The results obtained show that the hydroxyethylidene side chain at C(2) is pivotal to the stability of the different reaction products involved. The products with an open oxazolidine ring are more stable than those with a closed ring fused to the β‐lactam ring. This behaviour differs from that of penicillins and cephalosporins where the most stable degradation products are those with an intact thiazolidine or dihydrothiazine ring, respectively, fused to the β‐lactam ring. The different chemical reactivity of clavulanic acid relative to penicillins and cephalosporins could explain the disparate behaviour of the latter two types of compound towards β‐lactamases. Once the acyl‐enzyme intermediate of clavulanic acid has been formed, it can evolve with cleavage of the oxazolidine ring to form a difficult to deacylate compound.