Exploration of expanded carbohydrate chemical space to access biological activity using microwave-induced acid condensation of simple sugars

Complex glycans are ubiquitous in Nature and essential to life; glycosaminoglycans surround all mammalian cells and are key players in development and cell signalling, while plant cell walls provide structural rigidity, even during phases of growth, and plant cells account for the vast majority of carbon fixation on earth. Despite their diverse roles, however, only a fraction of the potential chemical space hypothetically available to complex glycans has been explored. New regions of this chemical space can, nevertheless, be accessed by generating new ones which do not occur in Nature or, by modifying naturally-occurring polysaccharide structures. Collectively, we term these new polysaccharides (NPs). Two synthetic routes to NPs are described here; the de novo route, directly from monosaccharide starting materials and the functionalization route, involving glycosylation of existing polysaccharides. The reaction in both cases involves a simple condensation step under microwave heating, catalysed by benign organic acids. The approach is illustrated by the generation of structures with biological activities ranging from cell signalling and inhibition of bacterial growth to mimicking carbohydrate antigens from pathogenic microorganisms. The method is as applicable to fine chemicals as it is to industrial waste, for example, biotechnologically-derived D-allulose (D-psicose) or biofermentation waste, and enables rapid access to extensive chemical space, encompassing both existing biological structures and those previously unattainable. Accessing this chemical space unlocks new functionalities and applications for complex glycans in the biological, medical, biotechnological and materials science arenas.