F. Seela, V. Sirivolu
Mar 1, 2007
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0
Influential Citations
70
Citations
Quality indicators
Journal
Helvetica Chimica Acta
Abstract
Oligonucleotides containing the 5-substituted 2′-deoxyuridines 1b or 1d bearing side chains with terminal CC bonds are described, and their duplex stability is compared with oligonucleotides containing the 5-alkynyl compounds 1a or 1c with only one nonterminal CC bond in the side chain. For this, 5-iodo-2′-deoxyuridine (3) and diynes or alkynes were employed as starting materials in the Sonogashira cross-coupling reaction (Scheme 1). Phosphoramidites 2b–d were prepared (Scheme 3) and used as building blocks in solid-phase synthesis. Tm Measurements demonstrated that DNA duplexes containing the octa-1,7-diynyl side chain or a diprop-2-ynyl ether residue, i.e., containing 1b or 1d, are more stable than those containing only one triple bond, i.e., 1a or 1c (Table 3). The diyne-modified nucleosides were employed in further functionalization reactions by using the protocol of the CuI-catalyzed Huisgen–Meldal–Sharpless [2+3] cycloaddition (‘click chemistry’) (Scheme 2). An aliphatic azide, i. e., 3′-azido-3′-deoxythymidine (AZT; 4), as well as the aromatic azido compound 5 were linked to the terminal alkyne group resulting in 1H-1,2,3-triazole-modified derivatives 6 and 7, respectively (Scheme 2), of which 6 forms a stable duplex DNA (Table 3). The Husigen–Meldal–Sharpless cycloaddition was also performed with oligonucleotides (Schemes 4 and 5).