Total Synthesis of WS9326B via a Bioinspired Macrolactonization Strategy

WS9326B (1) is a cycloheptadepsipeptide isolated from Streptomyces sp. SNM55 and is distinguished by its rare (Z)-pentenyl cinnamic acid side chain and notable antiangiogenic activity. Herein, we report its total synthesis through a bioispired macrolactonization strategy. Sequential amide couplings followed by Shiina esterification delivered WS9326B in 13 longest linear steps. This bioinspired synthesis provides a versatile platform for producing WS9326B and offers a distinctive perspective on macrocyclization strategy in complex cyclodepsipeptide synthesis, thereby facilitating future biological and medicinal investigations.