Gomes, PAraujo, MJRodrigues, MVale, NAzevedo, ZIley, JChambel, PMorais, JMoreira, R2015-12-302015-12-302004TETRAHEDRON. - Vol. 60, n. 26 (2004), p. 5551-55620040-4020http://hdl.handle.net/10451/21278The synthesis of imidazolidin-4-one derivatives of primaquine as potential antimalarial agents is described. The target compounds were synthesized in three steps: (i) condensation of (+/-)-primaquine with N-alpha-protected amino acids, (ii) removal of the N-alpha-protecting group, and (iii) reaction of the N-acylprimaquine with a carbonyl compound: acetone, three cyclic ketones and veratraldehyde. Using 2-formylbenzoic acid in the third step afforded 1H-imidazo[2,1-a]isoindole-2,5(3H,9bH)-diones. All products were isolated in good to excellent yields. Whereas imidazolidin-4-ones were formed as mixtures of all possible diastereomers in equal amounts, 1H-imidazo[2,1a]isoindole-2,5(3H,9bH)-diones were produced in a stereoselective fashion. The compounds hydrolyse very Slowly (t(1/2) 5-30 d) in pH 7.4 buffer to release primaquine. These primaquine derivatives are being submitted to biological assays, and preliminary results of their antimalarial activity are quite encouraging. (C) 2004 Elsevier Ltd. All rights reserved.application/pdfengChemistry, Organicjournal articlehttp://dx.doi.org/10.1016/j.tet.2004.04.077