From Pyridine to (-)-Agelastatin A

(-)-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.

Automated summary

(-)-Agelastatin A was synthesized by a flow photorearrangement of a pyridinium salt, which enabled the one-step construction of the desired cyclopentene core with specific functionalities and relative configurations. The enantiopure precursor to the natural product was obtained through a flow enzymatic kinetic resolution of the resulting bicyclic vinyl aziridine. This total synthesis utilized a single protective group. Two novel agelastatin N3-derivatives were synthesized and their cytotoxicity against various cancer cell lines was evaluated, confirming the significance of unsubstituted N3 in the biological activity of (-)-agelastatin A.