Amide-controlled, one-pot synthesis of tri-substituted purines generates structural diversity and analogues with trypanocidal activity
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AuthorPineda de las Infantas y Villatoro, María J.; Unciti-Broceta, Juan Diego; Contreras-Montoya, Rafael; García-Salcedo, José Antonio; Gallo Mezo, Miguel Ángel; Unciti-Broceta, Asier; Díaz-Mochón, Juan J.
Nature Publishing Group
Reaction mechanismsParasite biologyPurinesTrypanosoma bruceiTrypanocidal activity
Pineda de las Infantas y Villatoro, M.J.; et al. Amide-controlled, one-pot synthesis of tri-substituted purines generates structural diversity and analogues with trypanocidal activity. Scientific Reports, 5: 9139 (2015). [http://hdl.handle.net/10481/35509]
SponsorshipJ.J.D.M. thanks Spanish Ministerio de Economı´a y Competitividad for a Ramon y Cajal Fellowship. A.U.B. thanks MRC IGMM for an academic fellowship. This work was partially supported by Grant SAF2011-30528 to J.A.G.S..
Anovel one-pot synthesis of tri-substituted purines and the discovery of purine analogues with trypanocidal activity are reported. The reaction is initiated by a metal-free oxidative coupling of primary alkoxides and diaminopyrimidines with Schiff base formation and subsequent annulation in the presence of large N,N-dimethylamides (e.g.N,N-dimethylpropanamide or larger). This synthetic route is in competition with a reaction previously-reported by our group1, allowing the generation of a combinatorial library of tri-substituted purines by the simple modification of the amide and the alkoxide employed. Among the variety of structures generated, two purine analogues displayed trypanocidal activity against the protozoan parasite Trypanosoma brucei with IC50 , 5 mM, being each of those compounds obtained through each of the synthetic pathways.