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Mechanochemical Synthesis and Reactivity of 1,2,3-Triazole Carbohydrate Derivatives as Glycogen Phosphorylase Inhibitors

Author(s):

Naoufel Ben Hamadi*   Pages 1 - 5 ( 5 )

Abstract:


Aims: In this aim, we have developed this work to recommend an original route for the preparation of triazole derivatives.

Background: Carbohydrates containing 1,2,3-triazole derivatives have various biological activities. Due to their advantageous and biological property, they are eye-catching synthetic targets in the arsenal of organic chemistry. Thus, finding green and efficient methods, as well as using ball millig procedure for the synthesis of these heterocycles is of interest to organic chemistry researchers.

Objective: The objective of this study was to synthesize carbohydrate-derived triazoles under high-speed vibration milling conditions and investigate their properties.

Materials and Method: A mixture of glycoside azide derivatives (1 mmol) and prop-2-yn-1-ol (1.5 mmol) in the presence of copper (I) was vigorously shaken under vibration milling conditions at 650 rpm with three balls for 15 min. The deprotection of the resulting triazole derivatives was effected by treatment with 4M hydrochloric acid in methanol under reflux. Results and Discussion: A short and convenient route to synthesize carbohydrate-derived triazoles, based in a ball-mill via 1,3-dipolar cycloaddition reactions to prop-2-yn-1-ol was developed. Cleavage of the isopropylidene protecting group provided water-soluble triazoles, evaluated as glycogen phosphorylase inhibitors. 1-[6-(4-Hydroxymethyl-[1,2,3]triazol-1-yl)- 2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-yl]-ethane-1,2-diol was the best inhibitor of rabbit muscle glycogen phosphorylase b (IC50 = 60 μM).

Conclusion: In summary, we developed new, short and convenient routes to glucose-derived 1,2,3-triazole based on 1,3- dipolar cycloaddition reactions flowed by ball milling. Use of isopropylidene protective groups gave access to the analogous deprotected water-soluble motifs, analogous to known inhibitors of glycogen phosphorylase.

Keywords:

Ball milling, click chemistry, solvent-free, triazole, carbohydrate, phosphorylase inhibitors

Affiliation:

Laboratory of Synthesis Heterocyclic and Natural Substances, Faculty of Sciences of Monastir, Boulevard of Environment, 5000 Monastir



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