Tetrodotoxin Framework Construction from Linear Substrates Utilizing a Hg(OTf)-Catalyzed Cycloisomerization Reaction: Synthesis of the Unnatural Analogue 11--6,7,8-Trideoxytetrodotoxin.

In this contribution, we propose a new synthetic approach to tetrodotoxin (TTX), one of the most famous marine toxins that, after first preparing a functionalized linear substrate, forms a cyclohexane core from the substrate utilizing our mercuric triflate (Hg(OTf))-catalyzed cycloisomerization reaction. The concept was applied to the synthesis of 11--6,7,8-trideoxyTTX and 11--4,9-anhydro-6,7,8-trideoxyTTX, which are unnatural TTX analogues, demonstrating the validity of our new approach.