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

CASTRO, SEBASTIÁN J.; PADRÓN, JOSÉ M.; DARSES, BENJAMIN; NICOTRA, VIVIANA E.; DAUBAN, PHILIPPE

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY

WILEY-V C H VERLAG GMBH

Año: 2021

1434-193X

A 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 tumour 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 of late-stage C?H amination to improve the bioactivity of natural products.