Stereocontrolled Synthesis of (−)-5,11-Dideoxytetrodotoxin

Abstract

New derivatives of an intriguing marine natural product are now accessible. The first asymmetric synthesis of the simple tetrodotoxin analogue, 5,11-dideoxytetrodotoxin (3), was achieved. Hydroxylation at position C8 of the key intermediate 1 relied on the neighboring trichloroacetamide group, and stereoselective elaboration of the vinyl group gave alpha-hydroxylactone 2, which was transformed into the title compound through a new guanidylation method.