From Pyridine to (−)-Agelastatin A

Abstract

(−)-Agelastatin A was synthetized employing a flow photorearrangement of a pyridinium salt, constructing in one step the cyclopentene core possessing the desired functionalities and relative configurations. A flow enzymatic kinetic resolution of the resulting bicyclic vinyl aziridine delivered the enantiopure precursor to the natural product. This total synthesis required the use of a single protective group. Two novel agelastatin N3-derivatives were synthesized and their cytotoxicity evaluated against a series of cancer cell lines, which corroborated the importance of unsubstituted N3 in the biological activity of (−)-agelastatin A.