Fast and Efficient Mechanosynthesis of Aldonamides by Aminolysis of Unprotected Sugar Lactones

Abstract

Sugar amides, such as aldonamides, are interesting, sugar-based molecules used in various fields, from detergency to medicine. Nevertheless, their valorization, especially as alternatives to petroleum-based substances, can be slowed down by their synthetic pathway, which is generally not in accordance with green chemistry principles, and is also not economically competitive. We propose herein a fast procedure for the synthesis of aldonamide-derived glycoconjugates with mechanochemistry. The conditions were first optimized with galactonolactone, used as a model lactone, and dodecylamine. After only 5 min of grinding of stoechiometric amounts of amine and lactone, in the presence of water used as a Liquid Assisted Grinding (LAG) agent, the corresponding galactonamide was isolated with a high yield (90%) after a simple aqueous work-up. The optimized conditions were then applied to a wide variety of amines and sugar lactones, showing the versatility of the methodology. Gluco- and ribono-lactone exhibited similarly excellent reactivity, showing that the procedure is not sugar-dependent. Furthermore, the procedure was shown to be compatible with various functional groups such as alkene, alkyne, thiol, ester and hydroxyl.