Development of a Cryogenic Flow Reactor to Optimize Glycosylation Reactions Based on the Active Donor Intermediate

Abstract

The development of a continuous flow reactor for stereospecific glycosylation reactions with deoxy sugars is described. This apparatus that permits optimizing the selectivity of glycosylation reactions based on the stability of the activated intermediate is described. By coupling a flow apparatus with HPLC analysis, we can optimize the yield of TsCl-mediated β-linked deoxy sugar construction in a matter of hours. In all cases, results from continuous flow processing translate into improved results in batch-scale reactions, as demonstrated by competition experiments. This is the result of carrying out optimization to identify the ideal temperature for the reaction of the activated intermediate, as opposed to the initial activation conditions. Such an approach allows for the rapid development of highly selective glycosylation reactions in cases in which classical neighboring group participation is not possible.