Coene B, Schanck A, Dereppe J M, Van Meerssche M
J Med Chem. 1984 May;27(5):694-700. doi: 10.1021/jm00371a025.
The chemical reactivity of a series of cephalosporins is examined as a function of the substituents at positions 3 and 7. In most cases, the nature of the C7 side chain has a minor influence on the beta-lactam reactivity. But in the case of amino-containing C7 substituents, when intramolecular nucleophilic attack may occur, the reactivity may be greatly increased. The spectroscopic and structural characteristics of the beta-lactam linkage do not correlate with the chemical reactivity of studied compounds. The hydrolysis rates are linked neither with the IR frequency or 13C NMR chemical shift of the carbonyl beta-lactam nor with the geometry of the beta-lactam ring. However, a relationship is confirmed between the beta-lactam ring opening rate and the polarity of the C3-C4 double bond, reflected in the different 13C NMR chemical shifts of those atoms. The results are an experimental verification of the theoretical calculations of Boyd et al. on cephalosporin model compounds, which foresee that a C3 substituent could favor the opening of the beta-lactam cycle by stabilizing a transition state involved in alkaline hydrolysis.
研究了一系列头孢菌素的化学反应性与3位和7位取代基的关系。在大多数情况下，C7侧链的性质对β-内酰胺的反应性影响较小。但对于含氨基的C7取代基，当可能发生分子内亲核攻击时，反应性可能会大大增加。β-内酰胺键的光谱和结构特征与所研究化合物的化学反应性无关。水解速率既不与羰基β-内酰胺的红外频率或13C NMR化学位移相关，也不与β-内酰胺环的几何形状相关。然而，β-内酰胺环开环速率与C3-C4双键的极性之间的关系得到了证实，这体现在这些原子不同的13C NMR化学位移上。这些结果是对Boyd等人关于头孢菌素模型化合物理论计算的实验验证，该理论预测C3取代基可通过稳定碱性水解中涉及的过渡态来促进β-内酰胺环的开环。
