Synthesis Of The Bicyclo-[4.3.0]-Thymidyl-Nucleoside Via Pd(Ii)-Mediated Ring Expansion Chemistry

Abstract

A variety of modified nucleosides to improve antisense oligodeoxynucleotide properties such as target affinity, nuclease resistance, and pharmacokinetics were developed in the last two decades. In the context of conformational restriction we present here the synthesis of the [4.3.0]-bicyclo-DNA thymine monomer via Pd(II)-mediated ring expansion of an intermediate of the tricyclo-DNA synthesis.

Keywords:

• Antisense oligodeoxynucleotide properties
• target affinity
• nuclease resistance
• pharmacokinetics

Acknowledgments

The authors would like to thank the Swiss national Science Foundation (grant No. 200020-107692) for financial support of this project.