Application of Ball Milling Technology to Carbohydrate Reactions: I. Regioselective Primary Hydroxyl Protection of Hexosides and Nucleoside by Planetary Ball Milling

摘要

Dry ball milling of hexosides with trityl chloride in the presence of DABCO or Na_2CO_3 has been found to result in their complete conversion to the respective 6-O-trityl ethers. Further wet grinding of the reaction mixture with AC_2O in the presence of DMAP led to the respective fully protected hexosides in good to excellent yields after isolation. It has been found to be an effective one-pot two-step synthesis under solvent-free condition. The speed of homogenization has been shown to highly influence the rate and outcome of the reaction, and commercially available planetary ball mill has been proved to be very convenient for carrying out the reaction under standardized and reproducible conditions.