Total Synthesis and Structural Revision of Kasumigamide, and Identification of a New Analogue

Kasumigamide is an antialgal hybrid peptide–polyketide isolated from the freshwater cyanobacterium Microcystis aeruginosa (NIES‐87). The biosynthetic gene cluster was identified from not only the cyanobacterium but also Candidatus “Entotheonella”, associated with the Japanese marine sponge Discodermia calyx. Therefore, kasumigamide is considered to play a key role in microbial ecology, regardless of the terrestrial and marine habitats. We now report synthetic studies on this intriguing natural product that have led to a structural revision and the first total synthesis. During this study, a new analogue, deoxykasumigamide, was also isolated and structurally validated. This study confirmed the presence of the unusual pathway in the biosynthesis of a hybrid peptide–polyketide natural product. Revised: Kasumigamide (1) is an antialgal hybrid peptide‐polyketide isolated from the freshwater cyanobacterium M. aeruginosa (NIES‐87). The biosynthetic gene cluster was identified from not only the cyanobacterium but also a sponge symbiont. We now report synthetic studies on this intriguing natural product, leading to the structural revision, the first total synthesis, and identification of a new analogue of 1.