Introduction of Fluorine Into the C8 Position of Purine Nucleosides

Abstract

We have synthesized 2-amino-6,8-difluoro-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine (3) from 2-amino-6,8-dichloro-9-(2,3,5-tri-O-acetyl-ß-D-ribofuranosyl)purine (1) in a two-step procedure. The reaction of 3 with anhydrous ammonia in dry 1,2-dimethoxyethane gave 2,8-diamino-6-fluoro-9-(2,3,5-tri-O-acetyl-ß-D-ribofuranosyl)purine (4) in 64.1% yield. Compound 4 was deaminated with t-butylnitrite in tetrahydrofuran to give 2-amino-6-fluoro-9-(2,3,5-tri-O-acetyl-ß-D-ribofuranosyl)purine (6). The ¹H, ¹⁹F, and ¹³C NMR spectral data were determined and evaluated for each of the compounds.