Synthesis of 1,2,3-Triazole and Tetrazole Appended Glycoconjugates Based on 3,6-Anhydroglucofuranose via Click Reaction.

Abstract

Synthesis of <i>O</i>-glycosyl 1,2,3-triazoles and tetrazole based on the 3,6-anhydro-β-d-glucofuranoside core of natural sauropunols is reported herein. Toward the objective, <i>O</i>-glycosyl alkynes and nitriles, derived from easily available 3,6-anhydro-1,2-<i>O</i>-isopropylidene-5-<i>O</i>-benzoyl-α<i>-</i> d-glucofuranose using three different alcohols under the modified methanolysis procedure, were subjected to a click reaction using organic and inorganic azides. Subsequent introduction of azido and acetamido groups at C-2 of the sugar moiety and appropriate deprotection reactions involving excellent functional group tolerance with high stereo- and regioselectivity furnished ten 1,4-disubstituted and one 4-substituted 1,2,3-triazoles along with a 5-substituted tetrazole derivative with β-anomeric selectivity in good yields. The representative glycoconjugates displayed a high level of safety profile while tested in six cell lines using a cell viability assay. One of the compounds was also screened for aqueous solubility, liver microsomal stability across species, thereby demonstrating its pharmacologically relevant characteristics.