Coupled chemo(enzymatic) reactions in continuous flow

Yuryev, Ruslan; Strompen, Simon; Liese, Andreas

doi:10.3762/bjoc.7.169

Cited by 82 publications

(66 citation statements)

References 54 publications

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“…Several chemoenzymatic examples based on sequential catalytic reactions, achieved by spatial separation of the catalytic entities via flow chemistry are known from the literature 29,30 , but at the time of writing, there is a dearth of tandem reactions being described. The major challenges are the high complexity of the biomass-derived feedstock because of its heterogeneous composition and impurity, and catalyst activity, selectivity and stability.…”

Section: Nature Catalysismentioning

confidence: 99%

Opportunities and challenges for combining chemo- and biocatalysis

et al. 2018

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N ature has evolved highly efficient systems in the form of cascade reactions, which assemble the metabolic networks that support life (growth and survival). The basic principle of cascade reactions is also frequently used in biocatalysis, using enzymes in isolation, as well as in combination with chemocatalysts (see Fig. 1 and Box 1 for definition of terms) [1][2][3][4][5][6][7] . As there is no need for purification and isolation of intermediates, operating time, production costs and waste are reduced, and concomitantly, overall yields are improved. In addition, the problem of unstable or difficult to handle intermediates can be overcome, and reactivity as well as selectivity can be enhanced by avoiding unfavourable reaction equilibria through the cooperative effects of multiple catalysts 8 . Starting in the 1980s, the early examples of the combination of chemo-and biocatalysts were reported by the van Bekkum group, who pioneered the development of a process to make the sugar substitute d-mannitol from readily available d-glucose through the combination of a heterogeneous metal-catalysed hydrogenation and an enzyme-catalysed isomerization 9 . The first broadly applied technology for the combination of enzyme and metalcatalysts, which was the research subject of many academic groups as well as industry, emerged in the 1990s from the Williams group 10,11 and aimed to achieve higher yields than classical kinetic resolution of racemates, thus overcoming the limitation of a maximum yield of 50% in the latter case. A prominent example of work that developed this theme is the combination of lipase-catalysed kinetic resolution via acylation of secondary alcohols with Pd-or Rh-catalysed racemization via reversible transfer hydrogenation to achieve a dynamic kinetic resolution (DKR) [12][13][14] . This example was facilitated in part because lipases are active and stable in organic solvents. Later, for instance, Turner's group combined a monoamine oxidase-catalysed imine formation with a chemical reduction 15 to achieve the 100% theoretical yield through a deracemization process. In addition to the combination of metalcatalysis with enzymes, organocatalysis, electrochemistry and light-induced reaction couples have since then been studied extensively, going far beyond the scope of a DKR.The challenges to combining chemo-and biocatalysis in cascades (see Box 1 for definitions and Table 1) can be daunting, not least the requirement for the chemical step to occur in the presence of water, the preferred solvent for enzymes 3 . This Review therefore highlights recent examples of the combination of chemo-and biocatalysts in aqueous multistep syntheses, and looks at how to overcome limitations by, for example, design of appropriate reaction conditions, protein engineering and advanced reactor concepts. Furthermore, trends such as the integration of transition metalcatalysis into microorganisms and the introduction of novel chemistry into engineered enzymes are discussed, and a critical assessment of the impact of this research ...

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Section: Nature Catalysismentioning

confidence: 99%

Opportunities and challenges for combining chemo- and biocatalysis

et al. 2018

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“…Even today, most of biosynthetic operations are performed as a fixed, batch based single step procedure. Although continuous processes offer several advantages -such as facile automation, reproducibility and safety -the benefits of the flow-through approach [40][41][42][43][44][45] have not been fully exploited so far.…”

Section: Introductionmentioning

confidence: 99%

Lipase-Catalyzed Kinetic Resolution of 1-(2-Hydroxycyclohexyl)Indoles in Batch and Continuous-Flow Systems

et al. 2014

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The lipase catalysed kinetic resolution of three trans-1-(2-hydroxycyclohexyl)-indoles in both batch and continuous-flow systems is reported. Ring opening of cyclohexene oxide by the corresponding indole followed by enzymatic acylation with vinyl acetate resulted in novel, highly enantioenriched indole-substituted cyclohexanols and cyclohexyl acetates. The effect of the temperature on enantiomeric ratio (E) and productivity (specific reaction rate, r flow ) in the continuous-flow mode acylation was studied at analytical scale in the 0-70°C range.Preparative scale kinetic resolution of the three indole derivatives was performed in mixed continuous-and recirculation-flow mode resulting in almost complete conversion and good to excellent enantiomeric purity of the products.

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“…A recent publication reviewed the field of machine‐assisted coupled chemo(enzymatic) reactions in flow and commented on both the advantages and disadvantages of the process and where they perceive there to be future developments in this area 64. Others have focused on reactor design, particularly microstructured devices with enzymes to bring about improved biotransformations 65.…”

Section: Enzymesmentioning

confidence: 99%

Machine‐Assisted Organic Synthesis

et al. 2015

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In this Review we describe how the advent of machines is impacting on organic synthesis programs, with particular emphasis on the practical issues associated with the design of chemical reactors. In the rapidly changing, multivariant environment of the research laboratory, equipment needs to be modular to accommodate high and low temperatures and pressures, enzymes, multiphase systems, slurries, gases, and organometallic compounds. Additional technologies have been developed to facilitate more specialized reaction techniques such as electrochemical and photochemical methods. All of these areas create both opportunities and challenges during adoption as enabling technologies.

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Coupled chemo(enzymatic) reactions in continuous flow

Cited by 82 publications

References 54 publications

Opportunities and challenges for combining chemo- and biocatalysis

Opportunities and challenges for combining chemo- and biocatalysis

Lipase-Catalyzed Kinetic Resolution of 1-(2-Hydroxycyclohexyl)Indoles in Batch and Continuous-Flow Systems

Machine‐Assisted Organic Synthesis

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