Tetrodotoxin, a toxic principle of puffer fish poisoning, is a specific blocker of sodium channel. Despite many synthetic efforts since the structure elucidation in 1964, the only total synthesis of the racemic tetrodotoxin has been reported by Kishi and co-workers. In the course of our studies directed toward the total synthesis to analyze biologically interesting issues associated with tetrodotoxin, we accomplished a highly stereocontrolled synthesis of (-)-5,11-dideoxytetrodotoxin in 1999. Based on the synthesis, we describe herein the first total synthesis of 11-deoxytetrodotoxin, a naturally occurring analogue. The synthesis started from an allylic alcohol, the same intermediate for the synthesis of 5,11-dideoxytetrodotoxin. Epoxidation of the allylic alcohol was followed by isomerization with Ti(i-PrO)(4) to give an alpha-hydroxy allylic alcohol, in which the configurations of the two hydroxyl groups were inverted by oxidation and then a 2-step reduction. Further epoxidation of the allylic alcohol and ozonolysis of the remaining vinyl group gave an aldehyde, which reacted with magnesium acetylide to give a propargyl alcohol in a stereoselective manner. Oxidative cleavage of the acetylenic moiety with RuO(4) afforded a fully functionalized lactone for 11-deoxytetrodotoxin. Crucial guanidinylation was achieved from trichloroacetamide according to our own method to give acetyldibenzylguanidine. Finally, deprotection of benzyl groups, acetates, and acetal furnished 11-deoxytetrodotoxin.