Preparation of Potential Cell-Permeant Nucleoside-2′,3′-Cyclic Phosphate Precursors

Abstract

Uridine-3′-phosphorothiolate triesters bearing lipophilic moieties were prepared via Michaelis-Arbuzov chemistry. Subsequent deprotection of the S-cholesteryl phosphorothiolate triester afforded the corresponding diester which underwent spontaneous Cyclization to cleanly afford uridine 2′,3′-cyclic phosphate. This transesterification reaction could be expedited by treatment with iodine under mild, neutral conditions.

Keywords:

• Michaelis-Arbuzov
• cell-permeant
• phosphorothiolate
• cyclic phosphate
• precursor

Acknowledgments

This work was funded by the MRC (grant reference G0100461), the School of Chemistry, QUB and The Royal Society (grant reference 574006). We acknowledge Marie Migaud (QUB, Chemistry and Chemical Engineering) for useful discussions.