头孢菌素母核双键异构化的研究进展

Research Progress on Isomerization of Double Bond in Cephalosporin Pharmacophore

头孢菌素的Δ2异构体已被证实不具有抗菌活性,头孢菌素母核双键异构化将严重影响其药效。但在对头孢菌素进行结构修饰时,母核双键往往发生异构化,导致目标产物Δ3异构体不同程度地混有Δ2异构体。另外,前体药头孢菌素酯在体内水解时,部分Δ3异构体药物可能转化为Δ2异构体。本文综述了头孢菌素母核双键异构化机制,Δ3异构体和Δ2异构体的性质差异、合成及相互转化等研究进展。

The Δ^2 isomers of cephalosporin have been proved to be antibacterially inactive. However, the structural modification of cephalosporin may result in the isomerization of the double bond in the cephem nucleus. Sometimes the isomerization also occurs in the hydrolysis of the cephalosporin prodrug in vivo. In this paper, the research progress in the isomerization mechanism, the different properties, the synthesis and converse technology between the Δ^3 ceph-3-em and Δ^2 ceph-2-em, is reviewed.