Nucleosides and oligonucleotides with diynyl side chains: Base pairing and functionalization of 2 `-deoxyuridine derivatives by the copper(I)-catalyzed alkyne-azide `click' cycloaddition

Autor(en): Seela, Frank
Sirivolu, Venkata Ramana
Stichwörter: ACID RELATED-COMPOUNDS; ANTISENSE GENE INHIBITION; BIOLOGICAL-ACTIVITIES; Chemistry; Chemistry, Multidisciplinary; HELIX FORMATION; MODIFIED DNA; OLIGODEOXYNUCLEOTIDES; PYRIMIDINES; STABILITY; TERMINAL ALKYNES
Erscheinungsdatum: 2007
Herausgeber: WILEY-V C H VERLAG GMBH
Journal: HELVETICA CHIMICA ACTA
Volumen: 90
Ausgabe: 3
Startseite: 535
Seitenende: 552
Zusammenfassung: 
Oligonucleotides containing the 5-substituted 2'-deoxyuridines 1b or Id bearing side chains with terminal C C bonds are described, and their duplex stability is compared with oligonucleoticles containing the 5-alkynyl compounds la or le with only one nonterminal C C 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. T, 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 Id, 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 Cu-I-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).
ISSN: 0018019X
DOI: 10.1002/hlca.200790055

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