In recent years, there has been an increasing tendency to use biocatalysts in industrial chemistry, especially in the pharma and fine chemical sector. Preferably, enzymes or whole cells, applied as catalysts for a specific biotransformation, are utilized in aqueous reaction media since water is the natural medium for enzymes. In numerous examples of biocatalytic systems, however, a major problem is the insolubility of hydrophobic substrates in such aqueous reaction media. Apart from lipases, many enzymes are highly sensitive to organic solvents and are inactivated by an organic medium. Therefore, a change of solvent for biotransformations from water to organic solvents is usually challenging. In this study, we investigated the synthesis of nitriles by an organic solvent‐labile aldoxime dehydratase in pure organic solvents, exemplified for the dehydration of n‐octanaloxime to n‐octanenitrile. We present a method for applications in batch as well as flow mode based on an “immobilized aqueous phase” bearing the whole cells in a superabsorber as solid phase, thus enabling the use of a purely organic solvent as “mobile phase” and reaction medium.

As both, continuous synthesis and (bio-)catalysis gained increasing interest in research as well as for industrial applications, ways for merging these fields enables novel opportunities for modern sustainable process development. In this contribution, an alternative approach for the application of immobilized enzymes in continuous flow processes is presented utilizing heterogeneous biocatalysts as a mobile phase. Based on superabsorber-entrapped enzymes and whole cells as a "fluid heterogeneous phase", a segmented hydrogel/organic

A continuous‐flow dynamic kinetic resolution of racemic secondary alcohols was carried out using a single column reactor packed with a mixture of immobilized lipase and an immobilized oxovanadium species, VMPS4. As a result, optically pure esters were produced in 88–92 % yields. Problems encountered in this study were overcome by using fillers that efficiently maintained the initial distribution of the catalysts in the reactor and by using a packing method in which the mixing ratio of the two catalysts was varied in a stepwise fashion. The flow process led to an increased turnover number of each catalyst compared to those of batch reactions.

Flow processes and enzyme immobilization have gained much attention over the past few years in the field of biocatalytic process design. Downstream processes and enzyme stability can be immensely simplified and improved. In this work, we report the utilization of polymer network-entrapped enzymes and their applicability in flow processes. We focused on the superabsorber-based immobilization of an alcohol dehydrogenase (ADH) from Lactobacillus brevis and its application for a reduction of acetophenone. The applicability of this immobilization technique for a biotransformation running in a packed bed reactor was then demonstrated. Towards this end, the immobilized system was intensively studied, first in a batch mode, leading to >90% conversion within 24 h under optimized conditions. A subsequent transfer of this method into a flow process was conducted, resulting in very high initial conversions of up to 67% in such a continuously running process.were described by further groups using carrier-bound ADH from Lactobacillus brevis (LB-ADH) in combination with a mobile aqueous phase [30], or magnetic nanoparticle-bound ADH [31]. In addition, Buehler et al. investigated intensively the use of ADH in aqueous/organic segmented flow systems. It was shown that emulsion formation could be eliminated, and enzymatic mass transfer-limited reactions can be enhanced [32]. Furthermore, different means of stabilization of this reaction system were investigated [33]. Very recently, our group published an improved downstream process by means of such a segmented flow process, illustrated using two different ADHs and substrates [34].In continuous processes using packed bed reactors (PBR), catalyst immobilization is a prerequisite. Also, downstream processes benefit from immobilization, as separation of the reaction mixture from the catalyst is easier, and the catalyst reusability is improved [35]. Moreover, both, operational, as well as storage stability of the catalyst can potentially be significantly increased. However, often a significant loss of enzymatic activity during the immobilization process represents a drawback, and the reproducible production of immobilized catalyst may be a further challenge [36]. Numerous techniques have been developed over the past years, which can be classified in the following three major methods: (a) binding to a solid support (carrier), (b) entrapment (encapsulation) in polymer networks, or (c) cross-linking in the form of cross-linked enzyme aggregates (CLEAs) or cross-linked enzyme crystals (CLECs) [35]. Recently, much progress in the field of enzyme immobilization has been made [37][38][39][40][41].In this work, the option of entrapment of enzymes in polymer networks has been chosen. Often for this purpose, organic polymers containing cavities, sol-gel-processed particles, or membranes are used. A special case is the use of superabsorbent polymers to immobilize the entire aqueous phase. [42,43]. In this case, the enzyme is immobilized in its native aqueous environment, whereby undesired interact...

Reaction conditions have been identified to conduct a one-pot asymmetric organocatalytic aldol reaction with a hydrophobic substrate in aqueous medium via a process running in flow mode. By employing a mixture of water and 2-propanol, a hydrophobic aldehyde and 3.6 mol% of an organocatalyst, this microreactor process affords the desired aldol adduct with a conversion of 74% and an enantioselectivity of 89% after a reaction time of 60 minutes.