Reaction of acetyl hypofluorite with pyrimidines. Part 3. Synthesis, stereochemistry, and properties of 5-fluoro-5,6-dihydropyrimidine nucleosides

Abstract

The reaction of acetyl hypofluorite (AcOF) with unprotected uracil and cytosine nucleosides in acetic acid or water has been studied using ¹⁸F as a tracer. For the nucleosides in general two cis-diastereoisomers of both the 6-acetoxy-5-fluoro and 5-fluoro-6-hydroxy adducts were obtained, ¹H n.m.r. analysis of which showed that they all possessed the anti-conformation. The 6-acetoxy-5-fluoro adducts of the uracil nucleosides showed a remarkable stability and appeared to be interesting versatile compounds. They could be converted into their hitherto unknown corresponding 5-fluoro-6-hydroxy-O⁶,5′-anhydrocyclouracil nucleosides. For the cytosine nucleosides the 6-acetoxy-5-fluoro adducts were not observed, while the other cytosine adducts were found to rapidly deaminate at C-4 in water yielding the corresponding uracil analogues. Interestingly, even within a pair of diastereoisomers different deamination rates were observed.