Premium
The Degradation Mechanism of an Oral Cephalosporin: Cefaclor
Author(s) -
Vilanova Bartolomê,
Donoso Josefa,
Muñoz Francisco,
GarcíaBlanco Francisco
Publication year - 1996
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.19960790705
Subject(s) - chemistry , cephem , cefaclor , piperazine , lactam , aminolysis , high performance liquid chromatography , cephalosporin , degradation (telecommunications) , ring (chemistry) , moiety , intramolecular force , aqueous solution , nitrogen atom , stereochemistry , medicinal chemistry , organic chemistry , antibiotics , catalysis , telecommunications , carboxylic acid , biochemistry , computer science
The degradation of cefaclor ( 1 ), an oral cephalosporin antibiotic, was studied at 37° in a neutral aqueous medium by HPLC and 1 H‐NMR. Under these conditions, 1 underwent intramolecular aminolysis by the 7‐side‐chain NH 2 group on the β‐lactam moiety to give a piperazine‐2,5‐dione. The most prominent peak in the HPLC profile of a degradation solution from 1 was isolated by prep. HPLC. Mechanistically, the formation of this degradation product cis ‐ 11 from 1 involves the contraction from a six‐membered cephem ring to a five‐membered ring, which presumably takes place via a common episulfonium ion intermediate 9 (see Scheme ). Loss of the Cl‐atom from 3‐chloro‐3‐cephem is a general reaction subsequent to β‐lactam ring opening.