Tomato source: 12‐Oxophytodienoate reductase isoenzymes OPR1 and OPR3 from tomato possess a broad substrate spectrum for the asymmetric bioreduction of α,β‐unsaturated enals, enones, dicarboxylic ...acids, and N‐substituted maleimides (see scheme). Stereocomplementary behavior of both isoenzymes was observed in the reduction of a nitroalkene that led to the formation of opposite stereoisomers in high enantiomeric excess.
Within this paper, we present the design, development, and scale-up of a process for a continuous Matteson reaction to produce a key intermediate toward the β-lactamase inhibitor vaborbactam. This ...includes the successful implementation of the continuous concept at a multiton production scale for the API at Patheon, part of Thermo Fisher Scientific. The first-generation continuous flow production with its discontinuous downstream processing was further developed to a fully continuous production through installation of a continuous loop reactor. This enabled increased productivity and energy efficiency, eliminated volume and time bottlenecks, and reduced waste.
Three cloned enoate reductases from the “old yellow enzyme” family of flavoproteins were investigated in the asymmetric bioreduction of activated alkenes. 12‐Oxophytodienoate reductase isoenzymes ...OPR1 and OPR3 from Lycopersicon esculentum (tomato), and YqjM from Bacillus subtilis displayed a remarkably broad substrate spectrum by reducing α,β‐unsaturated aldehydes, ketones, maleimides and nitroalkenes. The reaction proceeded with absolute chemoselectivity – only the conjugated CC bond was reduced, while isolated olefins and carbonyl groups remained intact – with excellent stereoselectivities (ees up to >99%). Upon reduction of a nitroalkene, the stereochemical outcome could be determined via choice of the appropriate enzyme (OPR1 versus OPR3 or YqjM), which furnished the corresponding enantiomeric nitroalkanes in excellent ee. Molecular modelling suggests that this “enzyme‐based stereocontrol” is caused by subtle differences within the active site geometries.
Enoate reductases from the ‘old yellow enzyme’ family were employed for the asymmetric bioreduction of methyl 2‐hydroxymethylacrylate and its O‐allyl, O‐benzyl and O‐TBDMS derivatives to furnish ...(R)‐configurated methyl 3‐hydroxy‐2‐methylpropionate products in up to >99% ee Variation of the O‐protective group had little influence on the stereoselectivity, but a major impact on the reaction rate.
The asymmetric bioreduction of activated C-C-bonds catalyzed by a single flavoprotein was achieved via direct hydrogen transfer from a sacrificial 2-enone or 1,4-dione as hydrogen donor without ...requirement of a nicotinamide cofactor. Due to its simplicity, this system has clear advantages over conventional FAD-recycling systems.
Asymmetric bioreduction of α,β-unsaturated dicarboxylic acids, such as 2-methylmaleic/fumaric and 2-methylenesuccinic acid, as well as the corresponding dimethyl esters, using three cloned enoate ...reductases furnished 2-methylsuccinic acid or dimethyl 2-methylsuccinate, respectively. Opposite stereoisomeric products were obtained in up to >99% ee either by choice of the enzyme or by using E/Z-configurated substrates. Cofactor-recycling systems (NADH/FDH/formate, NADH/GDH/glucose or NADPH/G6PDH/glucose-6-phosphate) only worked in presence of a divalent metal ion, such as Ca2+, Mg2+, or Zn2+.
The traditional batch production of blocked polyisocyanates, key components in the preparation of self-cross-linking resins, has significant drawbacks associated with the exothermic character of the ...reaction and the high viscosity of some of the materials involved. We have developed a continuous flow strategy for the generation of a methyl ethyl ketoxime-blocked polyisocyanate. The neat oxime and the viscous polyisocyanate were pumped and mixed in continuous flow using a Kenics static mixer. The homogeneous mixture obtained was fully converted to the target blocked polyisocyanate in a residence time unit downstream of the mixer. Real-time reaction monitoring, via in-line Fourier-transform infrared analysis at the reactor outlet, has been implemented, enabling fast optimization of the reaction conditions and providing a sensitive and reliable method to control product quality. The process has been intensified in flow by stepwise increase of the temperature of the residence time unit. Full conversion after only 15 s of overall residence time has been achieved at 155 °C, providing a productivity of ca. 1 kg per hour for a reactor of only 4.5 mL volume. The ecological impacts of a conceptualized upscaled flow process compared to the industrial batch procedure have been evaluated by a comparative life cycle assessment (LCA) according to the ISO 14040/44 LCA framework. The LCA results illustrate the capabilities of continuous processing to enable more sustainable production of blocked polyisocyanates.
From active sites and stereospecificity: Active‐site structures of old yellow enzymes (OYEs) are correlated with their stereopreferences in the reduction of an aromatic nitroalkene, which leads to ...the identification of distinct clusters. These structural clusters are mapped onto sequence space, which yields four characteristic sequence motifs that may be used to cluster OYEs on the basis of their primary structure, as well as to predict their structural and biocatalytic properties.
Waterborne polyurethane dispersions (PUDs) have gained significant importance in the coating industry due to their diverse chemical and physical properties. However, a comprehensive analysis of their ...environmental impacts is lacking. Therefore, this study provides a comparative life cycle assessment (LCA) of four different PUD production processes from cradle-to-gate. The environmental performances of the NMP process, the acetone process, the melt process, and a conceptualized continuous flow process were evaluated and compared following the CML 2001 methodology. The LCA revealed that the conceptualized flow process exhibits the lowest environmental impact in all investigated impact categories. Depending on the impact category, the melt process or the acetone process rank second. The NMP process was observed to have the highest impact in all categories. Consequently, the flow process has the lowest carbon footprint (1.13 kg CO2-eq), according to the global warming potential (100 years), followed by the melt (1.45 kg CO2-eq), the acetone (1.95 kg CO2-eq), and the NMP process (3.11 kg CO2-eq).
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