The chemistry of dragmacidin alkaloids

Marine natural products have attracted considerable attention owing to their diverse biological activities and unique structural features. Among them, the dragmacidin alkaloids represent a structurally intriguing family of marine-derived natural products. These alkaloids exhibit a wide range of biological activities, including anticancer and antimicrobial activities, which have stimulated significant interest from both the chemical and biological communities. Structurally, they are characterized by highly functionalized bisindole frameworks in which two indole units are connected via a piperazine, pyrazine, or pyrazinone ring, and can be classified into three categories based on the nature of the linking unit: (i) dragmacidin and dragmacidins A, B, C, I, J, and didebromodragmacidin, featuring a piperazine linker; (ii) dragmacidins D, E, and F, containing a pyrazinone linker; and (iii) dragmacidins G and H, incorporating a pyrazine linker. These structural features pose formidable challenges for chemical synthesis, and consequently, the dragmacidin family has served as an important platform for the development of new synthetic strategies. In this chapter, we provide a comprehensive overview of the dragmacidin alkaloids, focusing on their isolation, structural features, biological activities, and synthetic studies.