Optimization of the Microwave Assisted Glycosylamines Synthesis Based on a Statistical Design of Experiments Approach

Abstract

Glycans carry a vast range of functions in nature. Utilizing their properties and functions in form of polymers, coatings or glycan derivatives for various applications makes the synthesis of modified glycans crucial. Since amines are easy to modify for subsequent reactions, we investigated regioselective amination conditions of different saccharides. Amination reactions were performed according to Kochetkov and Likhoshertov and accelerated by microwave irradiation. We optimized the synthesis of glycosylamines for N-acetyl-d-galactosamine, d-lactose, d-glucuronic acid and l-(−)-fucose using the design of experiments (DoE) approach. DoE enables efficient optimization with limited number of experimental data. A DoE software generated a set of experiments where reaction temperature, concentration of carbohydrate, nature of aminating agent and solvent were investigated. We found that the synthesis of glycosylamines significantly depends on the nature of the carbohydrate and on the reaction temperature. There is strong indication that high temperatures are favored for the amination reaction.

Keywords

• carbohydrates
• glycosides
• glycosylamines
• design of experiments (DoE)
• microwave chemistry
• amination