Unanticipated stereoselectivity in the reaction of primaquine alpha-aminoamides with substituted benzaldehydes: A computational and experimental study

• Tipo: Artigo em Revista Científica Internacional
• Data: 2007

Autores

Ricardo Ferraz (Autor) Outra; Jose R B Gomes (Autor) Outra; Eliandre de Oliveira (Autor) Outra; Rui Moreira (Autor) Outra; Paula Gomes (Autor) FCUP

Revista

Título: Journal of Organic Chemistry

Vol. 72

Páginas: 4189-4197

ISSN: 0022-3263

Editora: American Chemical Society

Indexação

ISI Web of Knowledge - 24 Citações

Scopus - 23 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Química

Outras Informações

ID Authenticus: P-004-A28

DOI: 10.1021/jo0703202

Abstract (EN): Imidazolidin-4-ones are commonly employed as skeletal modifications in bioactive oligopeptides, either as proline surrogates or for protection of the N-terminal amino acid against aminopeptidase- and endopeptidase-catalyzed hydrolysis. Imidazolidin-4-one synthesis usually involves the reaction of an alpha-aminoamide moiety with a ketone or an aldehyde to yield an imine, followed by intramolecular cyclization. We have unexpectedly found that imidazolidin-4-one formation is stereoselective when benzaldehydes containing o-carboxyl or o-methoxycarbonyl substituents are reacted with alpha-aminoamide derivatives of the antimalarial drug primaquine. A systematic computational and experimental study on the stereoselectivity of imidazolidin-4-one formation from primaquine alpha-aminoamides and various substituted benzaldehydes has been carried out, and they have allowed us to conclude that intramolecular hydrogen-bonds involving the CO oxygen of the o-substituent play a crucial role.

Idioma: Inglês

Tipo (Avaliação Docente): Científica