Synthesis of imidazolidin-4-one and 1H-imidazo[2,1-a]isoindole-2,5(3H,9bH)-dione derivatives of primaquine: scope and limitations

• Tipo: Artigo em Revista Científica Internacional
• Data: 2004

Autores

Gomes, P (Autor) FCUP; Araujo, MJ (Autor) FCUP; Rodrigues, M (Autor) Outra; Vale, N (Autor) Outra; Azevedo, Z (Autor) Outra; Iley, J (Autor) Outra; Chambel, P (Autor) Outra; Morais, J (Autor) Outra; Moreira, R (Autor) Outra

Revista

Título: Tetrahedron

Vol. 60

Páginas: 5551-5562

ISSN: 0040-4020

Editora: Elsevier

Indexação

ISI Web of Knowledge - 69 Citações

Scopus - 68 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Química

Outras Informações

ID Authenticus: P-000-9X0

DOI: 10.1016/j.tet.2004.04.077

Abstract (EN): The 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica