Press Releases

DATE2024.04.25 #Press Releases

Innovative technology for highly efficient production of oligonucleotide therapeutics!

--catalytic phosphite esterification reaction developed--

Aplil 25, 2024

A research group led by Professor Kobayashi at the Graduate School of Science, The University of Tokyo, has developed a new synthetic method for phosphite diesters that leads to efficient synthesis of oligonucleotide therapeutics. This achievement paves the way for the efficient production of oligonucleotide therapeutics with reduced environmental impact.

Oligonucleotide therapeutics with repeating phosphate ester structures are attracting attention as a new drug discovery modality, and currently 19 compounds are approved for the treatment of rare diseases. Oligonucleotide therapeutics have conventionally been synthesized in the solid-phase using a large excess of an activator as the key reaction, and there have been issues of environmental compatibility and scale-up. In this study, environmentally benign synthesis of phosphite diesters was achieved by using zinc complexes, which are Lewis acids, as catalysts. By combining the synthetic method developed in this study with oxidation reactions, phosphates can also be synthesized without isolation of intermediates, and catalytic synthesis of nucleotide dimers, the smallest building blocks of oligonucleotide therapeutics, was achieved.

The synthetic method developed in this study and its findings are expected to be applied to highly efficient catalytic liquid-phase synthesis of oligonucleotide therapeutics.

Figure: Synthesis of phosphate triester

For more details, please read the article:
Yuki Saito, Soo Min Cho, Luca Alessandro Danieli, Akira Matsunaga, and Shū Kobayashi* (* responsible author)
 2024. A Highly Efficient Catalytic Method for the Synthesis of Phosphite Diesters. Chemical Science.DOI: 10.1039/d4sc01401d.