A concise synthesis of tetrodotoxin

Konrad, David B.; Ruehmann, Klaus-Peter; Ando, Hiroyasu; Hetzler, Belinda E.; Strassner, Nina; Houk, Kendall N.; Matsuura, Bryan S. und Trauner, Dirk (2022): A concise synthesis of tetrodotoxin. In: Science, Vol. 377, No. 6604: pp. 411-415

Abstract

Tetrodotoxin (TTX) is a neurotoxic natural product that is an indispensable probe in neuroscience, a biosynthetic and ecological enigma, and a celebrated target of synthetic chemistry. Here, we present a stereoselective synthesis of TTX that proceeds in 22 steps from a glucose derivative. The central cyclohexane ring of TTX and its alpha-tertiary amine moiety were established by the intramolecular 1,3-dipolar cycloaddition of a nitrile oxide, followed by alkynyl addition to the resultant isoxazoline. A ruthenium-catalyzed hydroxylactonization set the stage for the formation of the dioxa-adamantane core. Installation of the guanidine, oxidation of a primary alcohol, and a late-stage epimerization gave a mixture of TTX and anhydro-TTX. This synthetic approach could give ready access to biologically active derivatives.

• Item Type: Journal article
• Faculties: Chemistry and Pharmacy > Department of Pharmacy
• Subjects: 500 Science > 540 Chemistry
• ISSN: 0036-8075
• Language: English