The synthesis of short phosphorodiamidate morpholino oligonucleotides (PMOs) has been
successfully achieved using azidoaryl carbamate protected chlorophosphoramidate monomers.
The deprotection step carried out in a neutral medium with triphenylphosphine-based
reagents avoids the need for chlorinated solvents. This method uses a meticulously
tailored combination of resin support, solvents, deblocking agents, and coupling reagents
to ensure efficient synthesis. Additionally, the azidoaryl carbamate protecting group
has been adapted as an orthogonal protection, enabling the development of bi- and
trifunctionalized PMOs for bioconjugation. These advancements are expected to broaden
the potential applications of PMOs in biomedical research.
Key words
antisense agents - oligonucleotides - protecting groups - conjugation - solid-phase
synthesis
