Late‐stage Rh(II)‐catalyzed Nitrene Transfer for the Synthesis of Guaianolide Analogs with Enhanced Antiproliferative Activity

Abstract

AbstractA set of new guaianolide derivatives (1–9) was obtained from ludartin, achalensolide, and 11,13‐dihydroachalensolide by application of catalytic nitrene transfer reactions. Intermolecular nitrene C(sp3)−H insertions led to the amination of C‐1, C‐2, and C‐10 positions, while alkene aziridination was also observed under these reaction conditions. The antiproliferative activity of natural compounds and their derivatives was evaluated against a panel of human solid tumor cell lines. The results show that an increase in the biological activity was observed following amination at the C‐2 position of Ludartin, thereby demonstrating the interest in late‐stage C−H amination to improve the bioactivity of natural products.