Cofactor-Driven Cascade Reactions Enable the Efficient Preparation of Sugar Nucleotides

Glycosylation is catalyzed by glycosyltransferases using sugar nucleotides or occasionally lipid-linked phosphosugars as donors. However, only very few common sugar nucleotides that occur in humans can be obtained readily, while the majority of sugar nucleotides that exist in bacteria, plants, archaea, or viruses cannot be synthesized in sufficient quantities by either enzymatic or chemical synthesis. The limited availability of such rare sugar nucleotides is one of the major obstacles that has greatly hampered progress in glycoscience. Herein we describe a general cofactor-driven cascade conversion strategy for the efficient synthesis of sugar nucleotides. The described strategy allows the large-scale preparation of rare sugar nucleotides from common sugars in high yields and without the need for tedious purification processes.