Nucleosides and Oligonucleotides with Diynyl Side Chains: Base Pairing and Functionalization of 2′-Deoxyuridine Derivatives by the Copper(I)-Catalyzed AlkyneAzide ‘Click’ Cycloaddition

✍ Scribed by Frank Seela; Venkata Ramana Sirivolu

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: German
• Weight: 404 KB
• Volume: 90
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.200790055

✦ Synopsis

Abstract

Oligonucleotides containing the 5‐substituted 2′‐deoxyuridines 1b or 1d bearing side chains with terminal CC bonds are described, and their duplex stability is compared with oligonucleotides containing the 5‐alkynyl compounds 1a or 1c 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~m~ 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 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 1__H__‐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).