Synthesis of Purine Nucleosides from <scp>D</scp>‐Glucuronic Acid Derivatives and Evaluation of Their Cholinesterase‐Inhibitory Activities

Abstract

Abstract Glucuronolactones were used as precursors for N 9 and N 7 purine nucleosides containing glucuronic acid derivatives in their structures. Acetylated N ‐benzylglucofuran‐ and glucopyranuronamides were synthesized in a few steps from glucofuranurono‐6,3‐lactone. They were converted into the corresponding furanosyl and pyranosyl uronamide‐based nucleosides by N ‐glycosylation with silylated 2‐acetamido‐6‐chloropurine in the presence of trimethylsilyl triflate. The triacetylated bicyclic lactone was coupled itself with the nucleobase to give bicyclic N 9 ,N 7 nucleosides. Tri‐ O ‐acetylglucopyranurono‐6,1‐lactone was used for the first time as a glycosyl donor for N ‐glycosylation, and led to β‐configured N 9 ‐ and N 7 ‐linked purinylglucuronides under reaction conditions similar to those used with the 1‐ O ‐acetyl‐substituted glycosyl donors. The cholinesterase inhibitory profiles of the synthetic nucleosides bearing glucuronic acid derivatives as glycons were evaluated, and they showed moderate selective acetylcholinesterase inhibitory activities ( K i = 14.78–50.53 μ M ). The best inhibition was shown by the furanosyl N 9 ‐linked uronamide‐based purine nucleoside.