Highly efficient multigram synthesis of 1,4:3,6-Dianhydro-α-D-glucopyranose by chemical synthesis methods: Development and scale-up study of synthetic routes

A reliable chemical synthesis method for the preparation of 1,4:3,6-dianhydro-alpha-D-glucopyranose (DGP) has been developed on the first time, with an overall four- step yield of 20 % on a 200g scale. The method for 2-OH regioselective benzylation protection of Methyl alpha-D-glucopyranoside was systematically optimized, providing a more scalable and cost-effective approach. The 3,6-anhydro pyranose intermediate was obtained through a two-step one-pot process. It has been confirmed that 2OH protection enhanced the ring stability of 3,6-anhydro pyranose and also found that the conformation of 3,6-anhydro pyranose indeed promoted the construction of 1,4-ether bonds. Overall, this work facilitated further application research of DGP in the fields of chemical synthesis, medicinal chemistry, and food chemistry.