Toward the synthesis of new endoperoxide derivatives with potential antimalarial activity, starting from cheap starting materials

International audienceElectron-rich cyclopropanes are known to give access to cyclic peroxides when oxidized in the presence of dioxygen.[1] In previous work, Yvan Six’s team had also shown that some α-amino endoperoxide derivatives prepared in this way exhibit siginificant antimalarial activity.[1b,2]In this project, we want to start from cheap electron-rich indole derivatives, and use copper catalysis to synthesize the corresponding aminocyclopropane products. After functional group modification, the latter will then be submitted to aerobic oxidation to give the desired cyclic endoperoxide targets (Scheme 1). We also wish to prepare a series of related molecules with various substitutions at positions 2 and 3 of the indole system.[1]a) K. Wimalasena, H. B. Wickman, M. P. D. Mahindaratne, Eur. J. Org. Chem. 2001, 3811−3817; b) C. Madelaine, Y. Six, O. Buriez, Angew. Chem. Int. Ed. 2007, 46, 8046–8049; c) Z. Lu, J. D. Parrish, T. P. Yoon, Tetrahedron 2014, 70, 4270−4278; d) F. Nuter, A. K. D. Dimé, C. Chen, L. Bounaadja, E. Mouray, I. Florent, Y. Six, O. Buriez, A. Marinetti, A. Voituriez, Chem. Eur. J. 2015, 21, 5584–5593.[2]C. Madelaine, O. Buriez, B. Crousse, I. Florent, P. Grellier, P. Retailleau, Y. Six, Org. Biomol. Chem. 2010, 8, 5591–5601