Teixobactin is a depsipeptide natural product with potent antibiotic activity against a range of Gram-positive multi-drug resistant bacteria. Its composition features a unique L-allo-enduracididine (allo-End₁₀), three Iles_2/6/11 residues, and one D-allo-Ile₅ residue. Intrigued by the potential biological impact of the stereochemistry of these residues, we synthesized teixobactin and three of its stereoisomers carrying L-End₁₀, D-End₁₀ or D-allo-End₁₀. In addition, stereoisomers with D-allo-Ile shuffled to positions 2, 6 or 11 were prepared. Our synthetic strategy uses the combined methods of solution and solid phase peptide synthesis. The solution phase synthesis overcomes the racemization issue for ester coupling between Ile₁₁ and Thr₈. The solid phase synthesis improves efficiency and convergence. This method also allows the efficient preparation of fluorescent-labeled analogs of teixobactin.

中文翻译：

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teixobactin及其立体异构体的全合成†

Teixobactin是一种十肽天然产物，对多种革兰氏阳性多药耐药细菌具有有效的抗生素活性。其组合物具有独特的大号-同种异体-enduracididine（同种异体-End ₁₀），三个尔斯_{11年2月6日}的残基，和一个d -同种异体-Ile ₅残基。由于这些残基的立体化学的潜在生物学影响，我们合成了teixobactin及其三个立体异构体，这些立体异构体带有L -End ₁₀，D -End ₁₀或D - allo -End ₁₀。此外，立体异构体d -同种异体-Ile改组，以位置2,6或制备11。我们的合成策略使用溶液和固相肽合成的组合方法。固溶相合成克服了Ile ₁₁和Thr ₈之间酯偶联的外消旋化问题。固相合成提高了效率和收敛性。该方法还可以有效制备荧光标记的替ixobactin的类似物。