Oligonucleosides with a Nucleobase-Including Backbone. Part 12 : Synthesis of Mixed Ethynylene-Linked Uridine- and Adenosine-Derived Tetramers

✍ Scribed by Simon Eppacher; Punit Kumar Bhardwaj; Bruno Bernet; José Luis Bravo Gala; Thomas Knöpfel; Andrea Vasella

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: German
• Weight: 201 KB
• Volume: 87
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.200490269

✦ Synopsis

Abstract

In contradistinction to the corresponding Grignard reagent, bis[(trimethylsilyl)ethynyl]zinc reacted with the 5′‐oxoadenosine 3 diastereoselectively to the β‐D‐allo‐hept‐6‐ynofuranosyladenine 5. Lithiation/iodination of the monomeric propargyl alcohol 5 and of the dimeric propargyl alcohol 22 provided the 8‐iodoadenosines 7 and 18, respectively, considerably shortening the synthesis of the dimeric O‐silylated 8‐iodoadenosine 25. The mixed uridine‐ and adenosine‐derived tetramers 21 and 32 were synthesised. The tetramer 21 was prepared by a linear sequence. Sonogashira coupling of 9 and 13 yielded the trimer 16 that was C‐desilylated to 17. A second Sonogashira coupling of 17 and 19 yielded the tetramer 21. Tetramer 32 was prepared in higher yields by a convergent route, coupling the acetylene 29 and the iodide 30. The uridine‐derived iodides proved more reactive than the adenosine‐derived analogues, and the N^6^‐unprotected adenosine‐derived alkynes were more reactive than their N^6^‐benzoylated analogues.