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

Frommer J., Müller S.

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'-O-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.

DOI

10.3762/bjoc.16.234

Type

Journal article

Publication Date

2020-01-01T00:00:00+00:00

Volume

16

Pages

2854 - 2861

Total pages

7

Keywords

RNA synthesis, Sonogashira reaction, nucleoside chemistry, protecting groups

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