Efficient Synthesis of Unprotected C-5-ArylHeteroaryl-2-deoxyuridine via a Suzuki-Miyaura Reaction in Aqueous Media.docVIP

Molecules 2012, 17, 14409-14417; doi:10.3390/molecules171214409 OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Efficient Synthesis of Unprotected C-5-Aryl/Heteroaryl-2-deoxyuridine via a Suzuki-Miyaura Reaction in Aqueous Media Nathalie Fresneau, Marie-Aude Hiebel, Luigi A. Agrofoglio and Sabine Berteina-Raboin * Institut de Chimie Organique et Analytique, Université d’Orléans, UMR CNRS 7311, BP 6759, 45067 Orléans Cedex 2, France * Author to whom correspondence should be addressed; E-Mail: sabine.berteina-raboin@univ-orleans.fr; Tel.: +33-2-3849-4856; Fax: +33-2-3841-7281. Received: 8 October 2012; in revised form: 20 November 2012 / Accepted: 23 November 2012 / Published: 5 December 2012 Abstract: Following our previous results on an environmentally benign one-pot Sonogashira-cyclization protocol to obtain substituted furopyrimidine nucleosides under aqueous conditions, we investigate herein the Suzuki-Miyaura cross-coupling reactions of aryl and heteroaryl derivatives at the C5 position of unprotected 2-deoxyuridine in the same media with a common catalyst system avoiding exotic ligands, since palladium acetate and triphenylphosphine afforded the expected products in moderate to good yields. Keywords: unnatural nucleosides; Suzuki-Miyaura coupling; aqueous conditions 1. Introduction Nucleosides attract attention due to the central role they play in all living systems. Therefore synthesis of unnatural nucleosides arises continuous interest because of their wide biological potential. For instance, 5-substituted 2-deoxyuridines have been reported as efficient candidates in DNA labeling, modification, and other studies [1–17], and they also exhibit significant antiviral [18–23], antibacterial [24], and anticancer activities [25–27]. Due to the importance of modified nucleosides, all major classes of palladium-catalyzed reactions have been extensively developed