Continuous synthesis of bromoalkyl glycosides by Fischer glycosylation in a microreactor

Abstract

In this study, bromoalkyl glycosides were successfully synthesized in microreactor scale by Fischer glycosylation. Yields between 24 and 40% after purification were achieved using various acidic catalysts and conditions. In some experiments, yields 180% higher than with previously known methods could be achieved. This study showed also that reversed-phase flash chromatography is more successful than normal-phase flash chromatography for the purification of bromoalkyl glycosides. Furthermore, longer bromoalcohols were shown to be more compatible than shorter bromoalcohols under these reaction conditions.

Like Visiting an Old Friend: Fischer Glycosylation in the Twenty-First Century: Modern Methods and Techniques

“…Microreactors are also a safer alternative for MW Fischer glycosylation, where a headspace is created through flammable alcohols, which represents an explosion hazard. Figure 13 shows the synthesis of bromoalkyl glucosides from d -glucose and bromoalcohols promoted by an acidic catalyst [ 59 ].

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“…The crude product was purified first with column chromatography, and after combining the fractions containing bromoalkyl glucosides, organic solvents were removed under reduced pressure to allow further refinement of the product with lyophilization. Anomeric ratios were detected with 1 H and 13 C NMR spectroscopy [ 59 ].

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“…[ 34 ]. Higher yields could be expected when more reaction solution is used, since the loss of a few hundred microliters would not impact the yield calculation as much [ 59 ].…”

Silane promoted glycosylation and its applications for synthesis of sugar compounds and active pharmaceutical ingredients (APIs)

“…However, TMSOTf assisted glycosylation yielded up to 40% bromoalkyl glycoside (121) in the scale-up process. 73 Vicenistatin is a novel 20-membered polyketide macrocyclic lactam antibiotic having antitumor activity against human colon carcinoma Co-3. 74,75 When polyene lactam (123) was glycosylated with 2-deoxy-glycosyl fluoride (122) in the presence of TMSOTf as the promoter, followed by the cleavage of the carbamate under basic pH, vicenistatin (124) and its a-anomer were produced in 10% and 18% yields, respectively (Scheme 31).…”

“…However, TMSOTf assisted glycosylation yielded up to 40% bromoalkyl glycoside ( 121 ) in the scale-up process. 73…”