Chemical synthesis is commonly seen as the final proof of the structure of complex natural products, but even a seemingly easy and well-established synthetic procedure may lead to an unexpected result. This is what happened with the synthesis of thermoactinoamide A (1a), an antimicrobial and antitumor nonribosomal cyclic hexapeptide produced by the thermophilic bacterium Thermoactinomyces vulgaris. The synthetic thermoactinoamide A outsourced to a company and the one described in a synthetic paper showed spectroscopic data identical to each other but different from those of the natural product. After a detailed spectroscopic, degradative, and synthetic study, the synthetic compound was shown to be an epimer (1b) of the intended target compound, originating during the cyclization reaction by extensive epimerization at the activated C-terminal amino acid. This allowed confirmation of the structure of the natural product.

中文翻译：

---

当合成出错时：使用 PyBOP 合成环肽 Thermoactinoamide A 时出现意外的差向异构化

化学合成通常被视为复杂天然产物结构的最终证明，但即使是看似简单且完善的合成程序也可能会产生意想不到的结果。这就是热放线菌酰胺 A ( 1a )的合成过程中所发生的情况，热放线菌酰胺 A (1a) 是由嗜热细菌普通热放线菌产生的一种抗菌和抗肿瘤非核糖体环状六肽。外包给一家公司的合成热放线菌酰胺 A 和一篇合成论文中描述的合成热放线菌酰胺 A 的光谱数据彼此相同，但与天然产物的光谱数据不同。经过详细的光谱、降解和合成研究，合成化合物被证明是预期目标化合物的差向异构体 ( 1b )，源自环化反应过程中活化的 C 末端氨基酸的广泛差向异构化。这使得可以确认天然产物的结构。