Amino acids as selective acylating agents: regioselective N-1-acylation of imidazolidin-4-one derivatives of the antimalarial drug primaquine

• Type: Article in International Scientific Journal
• Date: 2008

Authors

Nuno Vale (Author) FCUP; Joana Matos (Author) Other; Rui Moreira (Author) Other; Paula Gomes (Author) FCUP

Journal

Title: Tetrahedron

Vol. 64

Pages: 11144-11149

ISSN: 0040-4020

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 13 Citations

Scopus - 12 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: P-003-TSG

DOI: 10.1016/j.tet.2008.09.058

Abstract (EN): The acylation of bioactive primaquine-based imidazolidin-4-ones was studied using N-chi-Boc-protected glycine as acylating agent. Two synthesis routes, eight different coupling methods and seven distinct solvents were compared. Mild carbodiimide-based couplings on high dielectric constant solvents such as DMF or MeCN increased acylation yields, whereas alcohols inhibited carbodiimide-mediated acylations to take place. Achievement of the synthetic goals was limited by the size of the imidazolidin-4-one ring substituents R-1, R-2 and R-3, but resort to MW-assisted synthesis allowed overcoming such obstacle, though with very modest reaction yields. All reactions involving a Boc-protected amino acid were regioselective, independent of reaction conditions employed. In contrast, regioselective acetylation of the imidazolidin-4-ones could only be achieved by resort to very mild coupling procedures.

Language: English

Type (Professor's evaluation): Scientific