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Synthesis 2003(4): 0513-0522
DOI: 10.1055/s-2003-37652
PAPER
© Georg Thieme Verlag Stuttgart · New York

N-(Alkyl)-2-amino-1,4-pyrazine Derivatives: Synthesis and Antioxidative Properties of 3- and 3,5-p-Hydroxyphenyl-Substituted Compounds

Paul Jeanjota, Frédéric Bruyneela, Axelle Arraulta, Sonia Gharbia, Jean-François Cavaliera, Agnès Abelsa, Cécile Marchandb, Roland Touillauxc, Jean-François Reesb, Jacqueline Marchand-Brynaert*a
a Unité de Chimie Organique et Médicinale, Université Catholique de Louvain, Bâtiment Lavoisier, Place Louis Pasteur 1, 1348 Louvain-la-Neuve, Belgium
Fax: +(32)10474168; e-Mail: marchand@chim.ucl.ac.be;
b Unité de Biologie Animale, Université Catholique de Louvain, Bâtiment Carnoy, Place Croix du Sud 4, 1348 Louvain-la-Neuve, Belgium
c Unité de Chimie Structurale, Université Catholique de Louvain, Bâtiment Lavoisier, Place Louis Pasteur 1, 1348 Louvain-la-Neuve, Belgium
Further Information

Publication History

Received 25 November 2002
Publication Date:
07 March 2003 (online)

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Abstract

2-Amino-5-(p-hydroxyphenyl)-1,4-pyrazine and 2-amino-3,5-bis(p-hydroxyphenyl)-1,4-pyrazine are endowed with excellent antioxidative properties. For a possible development in medicinal chemistry, the lipophilicity of these lead compounds has to be increased. Therefore various methods of N-alkylation were systematically explored. The best results were obtained by quenching aminopyrazinyl anion with alkyl iodides, and by coupling aldehydes (reductive amination) in the presence of phenylsilane and tin catalyst.
Aminopyrazines equipped with linear alkyl side-chains of at least six carbons showed improved radical-scavenging properties in lipidic media.

Key words

pyrazines - alkylations - heterocycles - amines - reductions - antioxidants

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