Antimicrobial resistance is a serious threat to global human health; therefore, new anti‐infective therapeutics are required. The cyclic depsi‐peptide teixobactin exhibits potent antimicrobial activity against several Gram‐positive pathogens. To study the natural product's mechanism of action and improve its pharmacological properties, efficient chemical methods for preparing teixobactin analogues are required to expedite structure‐activity relationship studies. Described herein is a synthetic route that enables rapid access to analogues. Furthermore, our new N‐methylated analogues highlight that hydrogen bonding along the N‐terminal tail is likely to be important for antimicrobial activity.

中文翻译：

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骨架N-甲基化对Leu10-teixobactin构效关系的影响。

抗菌素耐药性是对全球人类健康的严重威胁；因此，需要新的抗感染疗法。环状Depsi肽teixobactin对多种革兰氏阳性病原体表现出强大的抗菌活性。为了研究天然产物的作用机理并改善其药理特性，需要有效的化学方法来制备teixobactin类似物，以加快结构-活性关系研究。本文描述了能够快速获得类似物的合成途径。此外，我们的新N-甲基化类似物突出表明，沿着N-末端尾部的氢键可能对抗菌活性很重要。