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

Abstract

Glucuronolactones were used as precursors for N⁹ and N⁷ 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 N⁹,N⁷ 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 N⁹‐ and N⁷‐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 μM). The best inhibition was shown by the furanosyl N⁹‐linked uronamide‐based purine nucleoside.