Microwave-assisted Serinol Dimethoxytritylation as a Key Step in Nucleic Acid Chemistry

Nucleic acids (DNA and RNA) have widespread applications in medicinal chemistry as well as in material sciences. It is possible to increase these applications and their efficacy by introducing chemical modifications. Such modifications bearing sequences are designated as artificial nucleic acids. Serinol Nucleic Acids (SNA) are artificial nucleic acids which differ from the natural DNA/RNA in their backbone structure. Their backbone contains serinol (2-amino-1,3-propanediol) monomers instead of ribose units. The serinol monomer must be in a suitable form for any DNA synthesizer to incorporate it into the DNA sequence. In that scope, the alcohol group at one end of the serinol monomer must be selectively protected. For DNA or RNA synthesis the nucleosides' alcohol groups are usually protected with 4,4’-dimethoxytrityl (DMTr) groups. ​​Thus protecting serinol's alcohol group with DMTr is an important step in artificial nucleic acid synthesis. However, traditional dimethoxytritylation reactions are consuming significant amounts of time and solvent. We therefore wondered if microwave heating could be applied for serinol protection reactions. Our experimental results give first evidence that microwave heating could be possibly used to protect serinol with 4,4'-dimethoxytrityl group and further optimization is necessary.