Synthesis of Phosphorodiamidate Morpholino Oligonucleotides (PMOs) Using Staudinger Reduction as a Deblocking Condition and Its Usefulness for Orthogonal Conjugation in Bi- and Trifunctionalized PMOs

Subhamoy Pratihar; Md Qasim; Surajit Sinha

doi:10.1055/a-2384-7323

Synlett, Table of Contents

Synlett 2024; 35(20): 2435-2440
DOI: 10.1055/a-2384-7323

letter

Special Issue to Celebrate the 75th Birthday of Prof. B. C. Ranu

Synthesis of Phosphorodiamidate Morpholino Oligonucleotides (PMOs) Using Staudinger Reduction as a Deblocking Condition and Its Usefulness for Orthogonal Conjugation in Bi- and Trifunctionalized PMOs

Subhamoy Pratihar

,

Md Qasim

,

Surajit Sinha∗

Abstract

All articles of this category

Abstract

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

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References

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