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Synthesis of Purine Nucleosides from D ‐Glucuronic Acid Derivatives and Evaluation of Their Cholinesterase‐Inhibitory Activities
Author(s) -
Xavier Nuno M.,
Schwarz Stefan,
Vaz Pedro D.,
Csuk René,
Rauter Amélia P.
Publication year - 2014
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201301913
Subject(s) - chemistry , stereochemistry , glucuronic acid , glycosyl donor , nucleoside , glycosyl , bicyclic molecule , lactone , purine , glycosylation , nucleobase , trifluoromethanesulfonate , enzyme , organic chemistry , biochemistry , catalysis , dna , polysaccharide
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.