The Chemistry and Biology of the Tetrodotoxin Natural Product Family.

Tetrodotoxin is a neurotoxic marine alkaloid, first isolated in 1909 from pufferfish and named after the biological order tetraodontiformes. Since its structural elucidation in 1964, it has attracted the interest of synthetic organic chemists due to its exceptional polarity, complex architecture, and important biological activity. This review highlights the diversity of the tetrodotoxin natural product family and discusses the origins of derivatives, biosynthetic hypotheses, and biological activities. Furthermore, potential therapeutic applications and structure-activity relationship studies are covered, along with the total syntheses of the natural product and selected derivatives that were published to date.