Unanticipated Stereoselectivity in the Reaction of Primaquine -Aminoamides with Substituted Benzaldehydes: A Computational and Exper

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• 作者：Ricardo Ferraz ; José ; R. B. Gomes ; Eliandre de Oliveira ; Rui Moreira ; Paula Gomes
• 刊名：Journal of Organic Chemistry
• 出版年：2007
• 出版时间：May 25, 2007
• 年：2007
• 卷：72
• 期：11
• 页码：4189 - 4197
• 全文大小：612K
• 年卷期：v.72,no.11(May 25, 2007)
• ISSN：1520-6904

文摘

Imidazolidin-4-ones are commonly employed as skeletal modifications in bioactive oligopeptides, eitheras proline surrogates or for protection of the N-terminal amino acid against aminopeptidase- andendopeptidase-catalyzed hydrolysis. Imidazolidin-4-one synthesis usually involves the reaction of an-aminoamide moiety with a ketone or an aldehyde to yield an imine, followed by intramolecularcyclization. We have unexpectedly found that imidazolidin-4-one formation is stereoselective whenbenzaldehydes containing o-carboxyl or o-methoxycarbonyl substituents are reacted with -aminoamidederivatives of the antimalarial drug primaquine. A systematic computational and experimental study onthe stereoselectivity of imidazolidin-4-one formation from primaquine -aminoamides and varioussubstituted benzaldehydes has been carried out, and they have allowed us to conclude that intramolecularhydrogen-bonds involving the C=O oxygen of the o-substituent play a crucial role.