Combining photochemical transformation of pyridinium salt with kinetic enzymatic resolution towards the total synthesis of (-)-agelastatin A

Abstract

Agelastatin alkaloids were synthesized through early-stage construction of the synthetically challenging C ring via photochemical transformation of pyridinium salts. Kinetic enzymatic resolution of bicyclic vinyl aziridines allowed the synthesis of (-)-agelastatin A in 4% yield over 12 steps. The cytotoxicity of (±)-agelastatin A and two N3-derivates were tested against a series of cancer cell lines to evaluate the impact of N3-substituition of the biological activity of agelastatin derivatives and corroborated the importance of unsubstituted N3 in the cytotoxicity of (-)-agelastatin A.