The semisynthetic derivatization of natural products is crucial for their continued development as antibiotics. While commercial pleuromutilin derivatives depend on amines for solubility, we demonstrate the high activity and solubility of oligoethylene glycol-substituted pleuromutilins achieved via a one-pot deprotection/attachment approach using thiolates protected as thioesters. The bifunctional linker synthesis is versatile and can be broadly applied to other chemistries. Antibacterial assays revealed this simple glycolate modification enhanced inhibition 4–8-fold relative to that of pleuromutilin. A new microscale solubility method is also introduced.

中文翻译：

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通过系统接头合成/一锅连接和微量溶解度方法获得高活性寡乙二醇 pleuromutilins


天然产物的半合成衍生化对于它们作为抗生素的持续发展至关重要。虽然商业 pleuromutilin 衍生物的溶解度依赖于胺，但我们证明了寡乙二醇取代的 pleuromutilins 的高活性和溶解度，方法是使用作为硫酯保护的硫醇酸盐的一锅脱保护/附着方法实现的。双功能接头合成用途广泛，可广泛应用于其他化学成分。抗菌试验显示，这种简单的乙醇酸盐修饰相对于 Pleuromutilin 增强了 4-8 倍的抑制作用。还介绍了一种新的微量溶解度方法。