Total synthesis of dysiherbaine

An efficient total synthesis of dysiherbaine, a potent and subtype-selective agonist for ionotropic glutamate receptors, has been achieved. An advanced key intermediate in the previous synthesis of neodysiherbaine A and its analogues was selected as the starting point, and cis-oriented amino alcohol functionality on the tetrahydropyran ring was installed by using an intramolecular SN2 cyclization of N-Boc-protected amino alcohol. The amino acid appendage was constructed by catalytic asymmetric hydrogenation of enamide ester.

An efficient synthetic route to dysiherbaine is described.