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

• Type: Article in International Scientific Journal
• Date: 2004

Authors

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

Journal

Title: Tetrahedron

Vol. 60

Pages: 5551-5562

ISSN: 0040-4020

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 69 Citations

Scopus - 68 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific