We report the synthesis of the antimicrobial cyclodepsipeptides marformycin A (1) and marformycin D (2) using a solid-phase approach. A scalable solution-phase synthesis of the γ-hydroxypiperazic acid subunit in 2, starting from cis-hydroxyproline, is also described. Structural analysis of 1 and its Leu-epi congener demonstrates conformational differences that may underlie their divergent antimicrobial activities. The described approach enables further development of conformation–activity relationships within this class of depsipeptide natural products.

中文翻译：

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Marformycins A 和 D 的全合成


我们报道了使用固相方法合成抗菌环肽马福霉素 A （1） 和马福霉素 D （2）。还描述了 2 中 γ-羟基哌嗪酸亚基的可扩展液相合成，从顺式羟基脯氨酸开始。1 及其 Leu-epi 同系物的结构分析表明了构象差异，这可能是它们不同的抗菌活性的基础。所描述的方法能够在这类 depsipeptide 天然产物中进一步发展构象-活性关系。