Synthesis and NMR Assignment of the Two Diastereomers of 8,6′-Cyclo-2′,6′-Dideoxyadenosine

Abstract

We herein present the first synthesis and characterization of the two C5′ diastereomers of 8,6′-cyclo-2′,6′-dideoxyadenosine. Starting from commercially available 2′-deoxyadenosine, the target cyclonucleosides were synthesized in 11 linear steps. Following a zinc-mediated cyclization reaction to form the seven-membered ring, the stereochemistry of the newly formed chiral center was established using two-dimensional NOESY NMR experiments.

[Supplemental materials are available for this article. Go to the publisher's online edition of Nucleosides, Nucleotides & Nucleic Acids for the free supplemental resource.]

Keywords:

• Cyclonucleosides
• conformationally restricted nucleosides
• 8,6′-cyclo-2′,6′-dideoxyadenosine
• DNA damage

Acknowledgments

We gratefully acknowledge funding from the NSF (MCB 0958515) for this research.