Biocatalytic Oxidation in Continuous Flow for the Generation of Carbohydrate Dialdehydes

Enzyme catalysis is gaining increasing importance in synthetic chemistry. Nowadays, the growing number of biocatalysts accessible by means of bioinformatics and enzyme engineering opens up an immense variety of selective reactions. Biocatalysis especially provides excellent opportunities for late‐stage modification often superior to conventional de novo synthesis. Enzymes have proven to be useful for direct introduction of functional groups into complex scaffolds, as well as for rapid diversification of compound libraries. Particularly important and highly topical are enzyme‐catalysed oxyfunctionalisations, halogenations, methylations, reductions, and amide bond formations due to the high prevalence of these motifs in pharmaceuticals. This Review gives an overview of the strengths and limitations of enzymatic late‐stage modifications using native and engineered enzymes in synthesis while focusing on important examples in drug development.

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“…This is of particular interest for the production of ADCs, but also applicable to other proteins. [ 263 , 264 , 265 ]…”

Section: Emerging Areas Of Late‐stage Modificationmentioning

confidence: 99%

Enzymatic Late‐Stage Modifications: Better Late Than Never

et al. 2021

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“…18,19 To overcome potential limitations of oxygen concentration, a previously described multipoint injection reactor (MPIR) was employed; it was shown to greatly improve the productivity of oxidase biocatalysts by negating low aqueous oxygen availability through in situ biocatalytic generation from hydrogen peroxide (Table 1). [20][21][22] An engineered choline oxidase (AcCO6) was initially chosen as an ideal biocatalyst to test in the MPIR due to its broad substrate scope and as it has been applied in biocatalytic cascades. 23,24 Using the MPIR, AcCO6 productivity was vastly improved for the oxidation of a number of aromatic and aliphatic primary alcohols with a 57.7 fold improvement in space time yield and 3.7 fold improvement in productivity in the oxidation of phenylethanol (see Supporting Information).…”

Section: Mainmentioning

confidence: 99%

Production of High Value Amine Intermediates via Biocatalytic Cascades in Continuous Flow

Mattey¹,

ford²,

Citoler³

et al. 2021

Preprint

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<div> <p>A key aim of biocatalysis is to mimic the ability of eukaryotic cells to carry out compartmentalized multistep cascades in a controlled and selective way. As biocatalytic cascades get longer and more complex, reactions become unattainable under typical batch conditions. Here a continuous flow multipoint injection reactor was combined with switching valves to overcome batch incompatibility, thus allowing for successful biocatalytic reaction cascades. As proof-of-principle, several reactive carbonyl intermediates were generated <i>in situ </i>using galactose oxidase and engineered choline oxidases, then passed directly to a series of packed-bed modules containing different aminating biocatalysts which accordingly produced a range of structurally distinct amines. The method was expanded to employ a batch incompatible sequential amination cascade <i>via </i>an oxidase-transaminase-imine reductase sequence, introducing different amine reagents at each step without cross reactivity. The combined approaches allowed for the biocatalytic synthesis of the natural product alkaloid precursor 4O-methylnorbelladine. The flow biocatalysis platform shown here significantly increases the scope of novel biocatalytic cascades, removing previous limitations due to reaction and reagent batch incompatibility.</p> </div> <b><br></b>

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“…For example, Turner and coworkers used directed evolution techniques to produce GOase variants that catalyze the oxidation of secondary alcohols ( Figure 9A; Escaletters and Turner, 2008) and amino alcohols (Herter et al, 2015; Figure 9B). Similarly, a GOase variant catalyzed the aerobic oxidation of lactose, a disaccharide formed as a waste stream (whey) in cheese manufacture, to form the dialdehyde (Figure 9C; Cosgrove et al, 2019). The latter is of interest as a raw material for polymers.…”

Section: Copper and Flavin Dependent Alcohol Oxidasesmentioning

confidence: 99%

Catalytic Oxidations in a Bio-Based Economy

Sheldon

2020

Front. Chem.

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The role of bio-and chemo-catalytic aerobic oxidations in the production of commodity chemicals in a bio-refinery is reviewed. The situation is fundamentally different to that in a petrochemicals refinery where the feedstocks are gaseous or liquid hydrocarbons that are oxidized at elevated temperatures in the vapor or liquid phase under solvent-free conditions. In contrast, the feedstocks in a biorefinery are carbohydrates that are water soluble solids and their conversion will largely involve aerobic oxidations of hydroxyl functional groups in water as the solvent under relatively mild conditions of temperature and pressure. This will require the development and use of cost-effective and environmentally attractive processes using both chemo-and biocatalytic methods for alcohols and polyols.

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Biocatalytic Oxidation in Continuous Flow for the Generation of Carbohydrate Dialdehydes

Abstract: This is a repository copy of Biocatalytic Oxidation in Continuous Flow for the Generation of Carbohydrate Dialdehydes.

Cited by 39 publications

References 35 publications

Enzymatic Late‐Stage Modifications: Better Late Than Never

Enzymatic Late‐Stage Modifications: Better Late Than Never

Production of High Value Amine Intermediates via Biocatalytic Cascades in Continuous Flow

Catalytic Oxidations in a Bio-Based Economy

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