Industrial Chemical Glycan Synthesis (ICGS): Process Intensification of Glycosylations

The industrial production of biologically active glycans is pivotal to the development and manufacture of glycan-based medicinal products. Chemical synthesis is critical to acquiring well-defined glycans for glycobiology investigations and the advancement of glycan-enabled applications. Efforts toward industrial chemical glycan synthesis (ICGS) are hampered by unique challenges associated with their structural complexity and diversity. The major bottleneck in ICGS are regio- and stereoselective glycosylations. In this Perspective, we review the process intensification of glycosylations based on innovative methodologies and devices, and highlight its contributions to ICGS. Five topics including optimization of glycan assembly sequence, modulation of glycosylation reactivity, adjustment of environmental parameters, development of an automated chemical glycan synthesizer, and application of artificial intelligence (AI) to glycan synthesis will be discussed. We also present prospects for accelerating ICGS through process intensification of glycosylation, including the integration of AI techniques, the development of glycosylation-oriented special large-scale reactors and flow chemistry platforms.