Identification of Tricyclic Guanidino Compounds from the Tetrodotoxin-Bearing Newt Taricha granulosa

The biosynthesis of the potent neurotoxin tetrodotoxin (TTX, 1) is still unresolved. We used MS-guided screening and nuclear magnetic resonance analyses including long-range HSQMBC to characterize two novel skeletal tricyclic guanidino compounds, Tgr-288 (2a and 2b) and Tgr-210 (3), from the TTX-bearing newt, Taricha granulosa. The presence of these compounds in toxic newts is congruent with a previously proposed pathway for TTX biosynthesis in terrestrial organisms that includes a monoterpene precursor and the production of structurally diversified guanidino compounds.