Changed reactivity of secondary hydroxy groups in C8-modified adenosine - lessons learned from silylation

Synthesis of site-specifically modified oligonucleotides has become a major tool for RNA structure and function studies. Reporter groups or specific functional entities are required to be attached at a pre-defined site of the oligomer. An attractive strategy is the incorporation of suitably function...

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Bibliographic Details
Published in:Beilstein journal of organic chemistry 2020-11, Vol.16 (1), p.2854-2861
Main Authors: Frommer, Jennifer, Müller, Sabine
Format: Article
Language:English
Subjects:
Chemistry
Full Research Paper
nucleoside chemistry
protecting groups
rna synthesis
sonogashira reaction
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Summary:Synthesis of site-specifically modified oligonucleotides has become a major tool for RNA structure and function studies. Reporter groups or specific functional entities are required to be attached at a pre-defined site of the oligomer. An attractive strategy is the incorporation of suitably functionalized building blocks that allow post-synthetic conjugation of the desired moiety. A C8-alkynyl-modified adenosine derivative was synthesized, reviving an old synthetic pathway for iodination of purine nucleobases. Silylation of the C8-alkynyl-modified adenosine revealed unexpected selectivity of the two secondary sugar hydroxy groups, with the 3'- -isomer being preferentially formed. Optimization of the protection scheme lead to a new and economic route to the desired C8-alkynylated building block and its incorporation in RNA.
ISSN:1860-5397
1860-5397
DOI:10.3762/bjoc.16.234