An improved synthesis of guanosine TNA phosphoramidite for oligonucleotide synthesis

Abstract

The chemical synthesis of guanosine nucleosides generates both the N9 and N7 regioisomers, which require careful separation to obtain the desired N9 isomer. To preferentially obtain the N9 isomer, a bulky diphenylcarbamoyl (DPC) group can be installed at the O6 position of guanine. However, installation of the DPC group presents a challenging task due to low solubility of the N-acetyl protected guanine. Here we report the usage of commercially available 2-amino-6-chloro purine as a new strategy that offers a more efficient route to the synthesis of the guanine phosphoramidite of threose nucleic acid (TNA).

Keywords:

• Threose nucleic acid
• phosphoramidites
• coupling efficiency
• solid-phase oligonucleotide synthesis

Acknowledgments

We wish to thank members of the Chaput lab for helpful comments and suggestions on the manuscript and Y. Jia for help with compound characterization.

Authors’ contribution

BM, DS, EL, and NS performed the experiments and analyzed the data. All authors contributed to manuscript writing.

Disclosure statement

The authors have no financial disclosures.

Supporting information

This document includes spectra of the synthesized compounds (¹H, ¹³C and HRMS).

Additional information

Funding

This work was supported by X, The Moonshot Factory.