Acid-mediated reactions under microfluidic conditions: A new strategy for practical synthesis of biofunctional natural products

Abstract

SummaryMicrofluidic conditions were applied to acid-mediated reactions, namely, glycosylation, reductive opening of the benzylidene acetal groups, and dehydration, which are the keys to the practical synthesis of N-glycans and the immunostimulating natural product, pristane. A distinctly different reactivity from that in conventional batch stirring was found; the vigorous micromixing of the reactants with the concentrated acids is critical especially for the “fast” reactions to be successful. Such a common feature might be due to the integration of all favorable aspects of microfluidic conditions, i.e., efficient mixing, precise temperature control, and the easy handling of the reactive intermediate by controlling the residence time. The microfluidic reactions cited in this review indicate the need to reinvestigate the traditional or imaginary reactions which have so far been performed and evaluated only in batch apparatus, and therefore they could be recognized as a new strategy in synthesizing natural products of prominent biological activity in a “practical” and a “industrial” manner.

Chemical reactivity and solution structure: on the way to a paradigm shift?

“…Although many of his predictions remain valid, one has to point out that recent development of micro-ow chemistry (another name -microuidic chemistry; for more details see the section on micro-ow chemistry below) revealed a possibility of a distinctly different reactivity pattern 8,[27][28][29] of a given compound under microuidic conditions from that exhibited by the same compound under conventional batch stirring. In fact, the use of microuidic technology unveiled new, previously unknown, chemical properties of known compounds involved in seemingly the same known reactions but performed under microuidic conditions.…”

Oligosaccharide Synthesis on Solid, Soluble Polymer, and Tag Supports

“…They have circumvented the problems by using the microfluidic systems and realized the quantitative a-sialylation with perfect a-selectivity, even in a large scale. Significantly, improved glycosylation could be achieved not only for a-sialylation but also for b-mannosylation 40 and N-glycosylation, 104 and the combination of these microfluidic glycosylation [105][106][107] and the solid-supported glycoslylation led to the successful synthesis of complex-type N-glycan with sialic acid as described in Section 16.2.3 (Scheme 16.16).…”

Asymmetric Reactions in Flow Reactors

“…Effi cient micromixing accelerated the reaction and the rapid heat transfer avoided the undesired hydrolysis and glycal formation. Similarly, selective β -mannosylated glucose has been obtained from a mixture of α / β -anomer of glucose [22] . α -Mannosylations have also been described [23] .…”