A Nucleotide Dimer Synthesis Without Protecting Groups Using Montmorillonite as Catalyst

Abstract

A synthesis has been developed providing nucleotide dimers comprising natural or unnatural nucleoside residues. A ribonucleoside 5′-phosphorimidazolide is added to a nucleoside adsorbed on montmorillonite at neutral pH with the absence of protecting groups. Approximately 30% of the imidazolide is converted into each 2′-5′ dimer and 3′-5′ dimer with the rest hydrolyzed to the 5′-monophosphate. Experiments with many combinations have suggested the limits to which this method may be applied, including heterochiral and chimeric syntheses. This greener chemistry has enabled the synthesis of dimers from activated nucleotides themselves, activated nucleotides with nucleosides, and activated nucleotides with nucleotide 5′-monophosphates.

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

Keywords:

• Montmorillonite
• phosphorimidazolide
• RNA dimers
• green chemistry

Acknowledgments

5-Fluoro-uridine was a gift from the Dayang Chemical Company. D-Xyloadenosine was a gift from Dr Gilles Gosselin. Volclay SPV-200 was a gift from the American Colloid Co., Arlington Heights, IL. This research was supported by NASA Astrobiology Institute grant NNA09DA80A. The purchase of the Bruker Ultraflex III MALDI-TOF-TOF mass spectrometer (Bruker Daltonics, Bremen, Germany) used in this work was made possible by the Gen*NY* sis (Generating Employment through New York State Science) program.