Synthesis 2011(4): 603-610  
DOI: 10.1055/s-0030-1258397
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Novel 5-(N-Alkylaminouracil) Acyclic Nucleosides

Sławomir Boncela, Andrzej Gondelaa, Maciej Mączkaa, Magdalena Tuszkiewicz-Kuźnika, Przemysław Greca, Barbara Hefczycb, Krzysztof Walczak*a
a Silesian University of Technology, Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Krzywoustego 4, 44-100 Gliwice, Poland
Fax: +48(32)2372094; e-Mail: [email protected];
b Silesian University of Technology, Department of Chemical Organic Technology and Petrochemistry, Krzywoustego 4, 44-100 Gliwice, Poland
Further Information

Publication History

Received 22 November 2010
Publication Date:
12 January 2011 (online)

Abstract

Protocols for the two-step syntheses of new 5-(N-hydroxyalkyl- and 5-N-benzylamino)uracil acyclic nucleosides bearing various functional groups (alkoxy/hydroxy and cyano/ester) are presented. Two groups of the title compounds were synthesised via aminolysis of 5-bromouracil and, subsequently, either coupling with an alkylating agent (2-chloromethoxyethyl acetate), or Michael­-type addition to acrylonitrile/methyl acrylate. The reverse sequences for both syntheses were also studied. The target molecules were designed as non-nucleoside reverse transcriptase inhibitors (NNRTI) and are analogues of 1-(hydroxyethoxymethyl)-6-thiophenylthymine (HEPT) and 3-benzyl-1-cyanomethyluracils. The obtained compounds will be used in screening tests for anti-HIV-1 activity.

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