Synthesis of methyl 3,4-anhydro-6-bromo-2-O-tert-butyldimethylsilyl-6-deoxy-α-D-allopyranoside from α-D-glucose

Abstract

Some of simple carbohydrates and their derivatives are used clinically for the treatment of various diseases. Epoxide derivatives, which can be obtained by the intramolecular elimination of water from two vicinal hydroxyl groups, are stable, but sufficiently reactive compounds very often used as intermediaries in various syntheses. Synthesis of epoxide derivative, methyl 3,4-anhydro-6-bromo-2-O-tert-butyldimethylsilyl-6-deoxy-α-D-allopyranoside from α-D-glucose was achieved in high yields in the minimal number of synthetic steps. Anhydrous glucose was used as a starting material which was transformed into methyl α-D-glucopyranoside using dry, gaseous hydrogen chloride. Thus obtained derivative was treated with benzaldehyde in the presence of zinc chloride as Lewis acid giving methyl (R)-4,6-O-benzylidene-α-D-glucopyranoside. Obtained compound was treated with NBS (N-bromosuccinimide) in dichloromethane in the presence of barium carbonate giving methyl 4-O-benzoyl-6-bromo-6-deoxy-α-D-glucopyranoside. In the next step obtained compound was treated with TBDMSCl (tert-butyldimethylsilyl chloride) in pyridine, and methyl 4-O-benzoyl-6-bromo-2-O-tert-butyldimethylsilyl-6-deoxy-α-D-glucopyranoside was further mesylated, and obtained methyl 4-O-benzoyl-6-bromo-2-O-tert-butyldimethylsilyl-6-deoxy-3-O-mesyl-α-D-glucopyranoside was treated at the end with KOH to give methyl 3,4-anhydro-6-bromo-2-O-tert-butyldimethylsilyl-6-deoxy-α-D-allopyranoside (yield 78 %).