Regioselective facile synthesis of novel isoxazole-linked glycoconjugates

Abstract

A concise and efficacious protocol for the regioselective synthesis of novel 3,5-disubstituted isoxazole-linked glycoconjugates (4, 7 and 9) via a 1,3-dipolar cycloaddition reaction between in situ generated glycosyl-β-nitrile oxide (derived from glycosyl-β-nitromethane ester 3 and 6) and various terminal alkynes bearing sugar, alkyl and aryl substituents (2a-n), has been devised. The formation of nitrile oxide during the reaction course has been supported by DFT calculations, which gave the optimized structure of the glycosyl-β-nitrile oxide ester. This one-pot methodology offers a way for utilizing d-glucose derived nitrile oxide, as a new variant in click chemistry for the synthesis of novel isoxazole-linked glycoconjugates, paving a new route for the construction of carbohydrate based scaffolds of multifaceted biological profiles. © 2015 Royal Society of Chemistry.