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Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

机译:Enduracididine,肽类抗生素中罕见的氨基酸成分:天然产物和合成

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摘要

Rising resistance to current clinical antibacterial agents is an imminent threat to global public health and highlights the demand for new lead compounds for drug discovery. One such potential lead compound, the peptide antibiotic teixobactin, was recently isolated from an uncultured bacterial source, and demonstrates remarkably high potency against a wide range of resistant pathogens without apparent development of resistance. A rare amino acid residue component of teixobactin, enduracididine, is only known to occur in a small number of natural products that also possess promising antibiotic activity. This review highlights the presence of enduracididine in natural products, its biosynthesis together with a review of analogues of enduracididine. Reported synthetic approaches to the cyclic guanidine structure of enduracididine are discussed, illustrating the challenges encountered to date in the development of efficient synthetic routes to facilitate drug discovery efforts inspired by the discovery of teixobactin.
机译:对当前临床抗菌剂的耐药性不断上升,这对全球公共健康构成了迫在眉睫的威胁,并突出了对用于药物发现的新型先导化合物的需求。一种这样的潜在的先导化合物,肽抗生素teixobactin,是最近从未经培养的细菌来源中分离出来的,显示出对多种耐药病原体的显着高效力,而没有明显的耐药性。 teixobactin的稀有氨基酸残基成分Enduracididine仅在少数天然产物中出现,这些天然产物也具有良好的抗生素活性。这篇综述着重介绍了天然产物中存在urendacididine,其生物合成以及enduracididine类似物的综述。讨论了报告的合成方法对环己啶的环状胍结构,说明了迄今为止在开发有效的合成途径以促进受teixobactin启发的药物发现方面遇到的挑战。

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