Green, microwave-assisted synthesis of O-perbutirylated-alkyl-glycosides

Carbohydrate chemical synthesis is a hard task that involves several protection and deprotection steps of hydroxyl groups to improve the regioselective formation of the glycosidic bond. Usually, this process is made through acylation reactions, where conventional heating and Lewis acids are used as promoters. However, these processes are time consuming, and sometimes catalysts disposal could represent an environmental problem. Given this, some alternatives to enhance the acylation process is the application of either microwaves and/or the use of other Lewis acids with less or null toxicity. Moreover, these approaches could be combined allowing to reduce reaction times and thus offering a “green” strategy synthesis for peracylated compounds. Thus, the present research proposes a green and fast alternative to produce peracylated glycosides through the synthesis of perbutyrilated sugars with potential to be used in enzymatic carbohydrate preparation. Model compound O-perbutirylated-phenyl-galactose was synthesized using imidazole as catalyst with different reaction conditions: at room temperature and assisted by microwaves. In the first case, reaction was held for 60 h, time required to totally consume the starting material according to TLC analysis. Then, modifications in perbutyrilation process and microwave assistance allowed to reduce to only 1 h for target sugar synthesis. NMR analyses confirmed that product formation was achieved with overall yields of 33% to reaction carried out at room temperature and 50% to microwave-assisted process. In conclusion, the combination of imidazole and microwaves is an excellent alternative to synthesize peracylated glycosides, which can be obtained swiftly and through a “green-chemistry” approach.