Synthesis of Bicyclo-DNA Nucleosides with Additional Functionalization in the Carbocyclic Ring

Abstract

Two novel bicyclo nucleoside isomers carrying the base thymine in the furanose ring and an ester substituent in the carbocyclic ring were synthesized from a common bicyclic sugar precursor via a cyclopropanation/fragmentation pathway in nine steps. The relative configuration of the ester substituent in both isomers as well as the anomeric configuration in one nucleoside was determined by 1H-NMR difference NOE spectroscopy.

Keywords

• Antisense oligonucleotides
• Bicyclo-dna
• Nucleosides
• Thymine
• Tricyclo-dna