ISSN:
0018-019X
Keywords:
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
Alkaline hydrolysis (pH 10.5) of the three 7-(oxyiminoacyl)cephalosporins 1a-c (cefuroxime, ceftazidime, and ceftriaxone) was studied at 37° using HPLC and 1H-NMR techniques. The 7-epicephalosporin 2, the 3-methylidene compound 3, and the 6-epimer 4 of the 3-methylidene compound 3 were identified for each cephalosporin as the major degradation products under the conditions used; ceftazidime (1b) yielded also the Δ2-isomer 5b (Scheme 1). A kinetic scheme was developed to account for the production of these compounds, and the different kinetic constants involved in the process were calculated. The experimental results show that the presence of a pyridinio group at position C-C(3) favours the appearance of the Δ2-isomer, which was detected mainly in cephalosporins bearing an ester function at C(4). The presence of an oxyimino group at C—CONH—C(7) facilitates epimerization at C(7) (→ 2), whereas that of an electron-withdrawing group at C—C(3) results in a increased formation constant for the 3-methylidene compound 3. The 3-methylidene compounds 3a-c produced by the three cephalosporins on cleavage of the β-lactam ring all underwent epimerization at C(6) to yield the corresponding 6-epimer 4.
Additional Material:
8 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/hlca.19930760805
