Oligonucleotide Analogues with Integrated Bases and Backbones. Part 24 : Synthesis, Conformational Analysis, and Association of Aminomethylene-Linked Self-Complementary Adenosine and Uridine Dinucleosides

✍ Scribed by Katja Chiesa; Alyena Shvoryna; Bruno Bernet; Andrea Vasella

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: German
• Weight: 535 KB
• Volume: 93
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.201000011

✦ Synopsis

Abstract

Inspection of Maruzen models and force‐field calculations suggest that oligonucleotide analogues integrating backbone and bases (ONIBs) with an aminomethylene linker form similar cyclic duplexes as the analogous oxymethylene linked dinucleosides. The self‐complementary adenosine‐ and uridine‐derived aminomethylene‐linked A*[n]U dinucleosides 15–17 were prepared by an aza‐Wittig reaction of the aldehyde 10 with an iminophosphorane derived from azide 6. The sequence‐isomeric U*[n]A dinucleosides 18–20 were similarly prepared from aldehyde 3 and azide 12. The N‐ethylamine 5, the acetamides 7 and 14, and the amine 13 were prepared as references for the conformational analysis of the dinucleosides. In contradistinction to the results of calculations, the N‐ethylamine 5 exists as intramolecularly H‐bonded hydroxyimino tautomer. The association in CDCl~3~ of these dinucleosides was studied by ^1^H‐NMR and CD spectroscopy. The A*[n]U dinucleosides 16 and 17 associate more strongly than the sequence isomers 19 and 20; the cyclic duplexes of 16 form preferentially Watson–Crick‐type base pairs, while 17, 19, and 20 show both Watson–Crick‐ and Hoogsteen‐type base pairing. The cyclic duplexes of the aminomethylene‐linked dinucleosides prefer a gg‐orientation of the linker. No evidence was found for an intramolecular H‐bond of the aminomethylene group. The CD spectra of 16 and 17 show a strong, those of 19 a weak, and those of 20 almost no temperature dependence.