Chapter 14 - Tetrodotoxin

Abstract

Tetrodotoxin (TTX) was isolated from puffer fish, used as speciality in Japanese cuisine, in 1909 from the ovaries and livers of fish, while its structure was elucidated in 1964 on the basis of Tsuda, Woodward, and Goto work that reported independently to identify and characterize the compound with polyfunctionalized dioxaadamantane skeleton, a cyclic guanidine containing a hemiaminal moiety with nine contiguous stereogenic centers (Goto et al., 1965). The TTX was found to be a potent selective blocker of voltage-gated sodium (Na+) channels (Choudhary et al., 2003). In 1970, Nitta et al. determine the absolute stereochemistry of TTS via X-ray crystallographic analysis of one of its derivatives (Furusaki et al., 1970). In acidic conditions, TTX exits as inseparable mixture of orthoester and lactone; therefore, the purification of the tetrodotoxin in final steps is a challenging issue. Later, Yasumoto and Yotsu-Yamashita have isolated many natural analogs of TTX from puffer fish and newts (Yotsu-Yamashita, 2001). Most of these natural derivatives consist of deoxy species and regard as biosynthetic intermediates or metabolites of tetrodotoxin. TTX with its potent biological activity and structure complexity has obtained much attention from chemist community to synthesize it.