Renaissance of Traditional Organic Reactions under Microfluidic Conditions: A New Paradigm for Natural Products Synthesis

Continuous flow synthesis for bioactive natural products is described. Efficient procedures using the microfluidic system were developed for the large-scale synthesis of important synthetic units of asparagine-linked oligosaccharide in glycoprotein. Advantageous aspects of microfluidic conditions, i.e., efficient mixing, fast heat transfer, and residence time control led to cation-mediated reactions, such as α-sialylation, β-mannosylation, and reductive opening of the benzylidene acetal groups in high yields. Microfluidic dehydration was developed for the industrial-scale synthesis of the immunostimulating natural terpenoid, pristane. The base-mediated aldol condensation in an aqueous biphasic system enabled the multigram synthesis of β-hydroxyketones in high yields.