Total Synthesis of Albicidin: A Lead Structure from Xanthomonas albilineans for Potent Antibacterial Gyrase Inhibitors
Total Synthesis of Albicidin: A Lead Structure from Xanthomonas albilineans for Potent Antibacterial Gyrase Inhibitors
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DOI：
10.1002/anie.201409584
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发表时间：
2015-02-02
影响因子：
16.6
通讯作者：
Suessmuth, Roderich D.
中科院分区：
文献类型：
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作者：
Kretz, Julian;Kerwat, Dennis;Suessmuth, Roderich D.
由植物病原菌白色黄单胞菌合成的多肽抗生素白化菌素对多种革兰氏阳性和革兰氏阴性菌具有显著的抗菌活性。从生产有机体或通过异源表达获得的少量白念珠菌素是为生物活性图谱和结构活性研究提供足够材料的限制因素。因此，我们开发了一条收敛的白念珠菌素全合成路线。芳香族氨基酸之间的酰胺键的形成出人意料地困难，这是通过三光气介导偶联策略实现的。本文介绍的白念珠菌素的合成证实了先前确定的化学结构，并强调了该化合物非凡的抗菌活性。合成方案将提供多克量的白化菌素，用于进一步分析其药物特性。
The peptide antibiotic albicidin, which is synthesized by the plant pathogenic bacterium Xanthomonas albilineans, displays remarkable antibacterial activity against various Gram-positive and Gram-negative microorganisms. The low amounts of albicidin obtainable from the producing organism or through heterologous expression are limiting factors in providing sufficient material for bioactivity profiling and structure-activity studies. Therefore, we developed a convergent total synthesis route toward albicidin. The unexpectedly difficult formation of amide bonds between the aromatic amino acids was achieved through a triphosgene-mediated coupling strategy. The herein presented synthesis of albicidin confirms the previously determined chemical structure and underlines the extraordinary antibacterial activity of this compound. The synthetic protocol will provide multigram amounts of albicidin for further profiling of its drug properties.