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

Journal article

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.

Authors: Frommer, J; Müller, S

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Beilstein-Institut
• Journal: Beilstein Journal of Organic Chemistry
• Volume: 16
• Pages: 2854-2861
• Publication date: 2020-11-23
• DOI: 10.3762/bjoc.16.234
• EISSN: 1860-5397
• ISSN: 1860-5397
• Language: English
• Keywords: Biochemistry; Organic chemistry; Chemistry; Silylation; Moiety; Stereochemistry; Reactivity (psychology); Oligonucleotide; Click chemistry; Combinatorial chemistry; Oligomer; Adenosine; Nucleobase; DNA; Catalysis