Synthesis and Cytotoxic Activity of Novel 5-Substituted-1-(β-L-Arabinofuranosyl) Pyrimidine Nucleosides

Abstract

A series of new 5-halogeno-1-(ß-L-arabinofuranosyl)uracils and their cytosine analogues were synthesized by halogenation of ara-L-uridine and ara-L-cytidine, respectively. The 5-(2-thienyl) and 5-halogenothienyl derivatives of both series were also prepared in excellent yields by Stille coupling followed by halogenation. All of these syntheses were based on benzoyl-protected derivatives. In vitro cytotoxicity experiments carried out using L1210 mouse leukemia cells showed that 5-(2-thienyl)-ara-L-uridine was the most potent compound of the new compounds; the majority of the analogues were not effective up to 200 μM concentrations.

Keywords:

• L-nucleosides
• 5-substituted pyrimidines
• halogenations
• cytotoxic activity

Acknowledgments

The authors are indebted to Mrs. Erzsébet Braun for her valuable assistance in the synthetic work and to Dr. Pal Szabo for the mass spectrometry analyses.