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HPLC and 1 H‐NMR Studies of Alkaline Hydrolysis of Some 7‐(Oxyiminoacyl)cephalosporins
Author(s) -
Vilanova Bartolomé,
Muñoz Francisco,
Donoso Josefa,
Blanco Francisco García
Publication year - 1993
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.19930760805
Subject(s) - chemistry , epimer , cephalosporin , hydrolysis , stereochemistry , lactam , high performance liquid chromatography , alkaline hydrolysis , ceftazidime , yield (engineering) , medicinal chemistry , organic chemistry , bacteria , antibiotics , biochemistry , materials science , biology , metallurgy , pseudomonas aeruginosa , genetics
Alkaline hydrolysis (pH 10.5) of the three 7‐(oxyiminoacyl)cephalosporins 1a–c (cefuroxime, ceftazidime, and ceftriaxone) was studied at 37° using HPLC and 1 H‐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 Δ 2 ‐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 Δ 2 ‐isomer, which was detected mainly in cephalosporins bearing an ester function at C(4). The presence of an oxyimino group at C CONHC(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 .