A general synthetic route to conjoint molecules of cephalosporins and aminoglycosides is described. These molecules were designed as potential substrates for bacterial β‐lactamases, enzymes that hydrolyze the β‐lactam bond of cephalosporins. Hydrolysis of the β‐lactam bond was expected to release the C10‐appended aminoglycoside. Since β‐lactamases are sequestered in the periplasmic space of gram‐negative bacteria, this sequence of events would liberate aminoglycoside inside such bacteria. It is expected that such local delivery of aminoglycosides would circumvent the inherent toxicity of aminoglycosides that occurs during systemic exposure within the mammalian host.

中文翻译：

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头孢菌素和氨基糖苷类联合分子

描述了联合头孢菌素和氨基糖苷类分子的一般合成路线。这些分子被设计为细菌 β-内酰胺酶的潜在底物，β-内酰胺酶水解头孢菌素的 β-内酰胺键。预计 β-内酰胺键的水解会释放出带有 C10 的氨基糖苷。由于 β-内酰胺酶被隔离在革兰氏阴性菌的周质空间中，这一系列事件将在此类细菌内释放氨基糖苷。预期氨基糖苷类的这种局部递送将规避在哺乳动物宿主内全身暴露期间发生的氨基糖苷类的固有毒性。