Programmable one-pot oligosaccharide synthesis

An improved process for synthesizing an oligosaccharide product, the oligosaccharide product having a linear sequence of four or more glycosyl units linked to one another by glycosidic linkages, the sequence starting with a first glycosyl unit at a nonreducing end, concluding with a final glycosyl unit at a reducing end, and including two or more intermediate glycosyl units sequentially arrayed between the first and final glycosyl units, the process employing the following steps:

• Condensing protected glycosyl donors or protected glycosyl donor/acceptors with protected glycosyl donor/acceptors or protected glycosyl acceptors for producing a protected oligosaccharide intermediate corresponding to the oligosaccharide product, and then
• Deprotecting the protected oligosaccharide intermediate for producing the oligosaccharide product;
• wherein the improvement comprises the following additional steps:
• Step A:
• providing a database of relative reactivity values for variously protected glycosyl donors corresponding to the first glycosyl unit and for variously protected glycosyl donor/acceptors corresponding to each of the intermediate glycosyl units and for variously protected acceptors corresponding to the final glycosyl unit, the variously protected glycosyl donors each having an activated anomeric carbon and lacking a free hydroxyl, the variously protected glycosyl donor/acceptors each having both an activated anomeric carbon and one free hydroxyl group, the variously protected acceptors having one free hydroxyl group and a blocked anomeric carbon;
• then
• Step B:
• from the database of said Step A, selecting a preferred glycosyl donor corresponding the first glycosyl unit, preferred donor/acceptors corresponding to each of the intermediate glycosyl units, and a preferred glycosyl acceptor corresponding the final glycosyl unit, the preferred glycosyl donor, each of the preferred glycosyl donor/acceptors, and the preferred accetpr being selected for optimizing condensation reactions leading to the production of the protected oligosaccharide intermediate;
• and then
• in said condensation step, the preferred glycosyl donor, the preferred donor/acceptors, and the preferred acceptor are added in a sequential fashion under condensation conditions for synthesizing the protected oligosaccharide intermediate in a one-pot synthesis, starting at the nonreducing end and progressing sequentially to the reducing end.