CARBOHYDRATES TO CARBOCYCLES - SYNTHESIS OF THE DENSELY FUNCTIONALIZED CARBOCYCLIC CORE OF TETRODOTOXIN BY RADICAL CYCLIZATION OF AN ANHYDRO SUGAR PRECURSOR

The core of tetrodotoxin is a densely functionalized carbocycle for which an annulated pyranose can be envisaged as a retron. The carbocyclic ring is constructed upon a rigid 1,6-anhydro template which permits the early introduction of the key angular nitrogen, and concomitantly positions a trap for reaction with a carbon-centered radical generated chemospecifically at C6. The carbocyclic entity is elaborated in this process leading to a caged system with the capability for generating all of the stereogenic centers. A novel procedure using tert-butylhyponitrite is described for C6 dehydrogenation pursuant to the intramolecular radical cyclization.