Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• only. This is facilitated when using heterogeneous catalysts or immobilized enzymes that are retained in cartridge reactors. For instance, Paradisi and co-workers reported an N-acetylation approach to produce melatonin analogs, where the pure product is obtained in the organic phase after evaporation

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• min isoamyl acetate (10) is obtained in 59% yield according to GC analysis [26]. Related methods for the enzyme-catalyzed acetylation of isoamyl alcohol (9) have been developed utilizing biphasic systems, supercritical carbon dioxide as a solvent, or packed-bed reactors with immobilized enzymes [27

Shift of the reaction equilibrium at high pressure in the continuous synthesis of neuraminic acid

• Jannis A. Reich,
• Miriam Aßmann,
• Kristin Hölting,
• Paul Bubenheim,
• Jürgen Kuballa and
• Andreas Liese

Beilstein J. Org. Chem. 2022, 18, 567–579, doi:10.3762/bjoc.18.59

• reasons, the synthesis of N-acetylneuraminic acid (Neu5Ac) in a continuous fixed-bed reactor by an immobilized epimerase and aldolase was investigated in detail. The immobilized enzymes showed high stability, with half-life times > 173 days under storage conditions (6 °C in buffer) and reusability over 50

• other analyzed loadings of the aldolase showed a lower yield of 70 mgenzyme/gcarrier (octadecyl methacrylate) and between 10–30 mgenzyme/gcarrier for the other evaluated carriers. The activity of the immobilized enzymes was analyzed in small scale batch experiments with a reaction volume of 1 mL. The

• methacrylate and aldolase: amino methacrylate). The microenvironment and material surrounding the enzyme have a significant influence on the enzyme activity [30]. For reusability studies, the three most appropriate carriers were selected and analyzed with respect to the activity of the immobilized enzymes

Asymmetric synthesis of a high added value chiral amine using immobilized ω-transaminases

• Antonella Petri,
• Valeria Colonna and
• Oreste Piccolo

Beilstein J. Org. Chem. 2019, 15, 60–66, doi:10.3762/bjoc.15.6

• excess starting from a commercial substrate. The reaction was carried out by using different commercially available immobilized enzymes, evaluating the catalytic activity and the enantioselectivity under different experimental conditions. Re-use of the most efficient enzyme was performed both in batch

• sustainable approach to an industrial scale. Keywords: asymmetric catalysis; biotransformations; chiral amine; immobilized enzymes; ω-transaminases; Introduction Enantiomerically pure amines are important precursors to biologically active compounds with different industrial applications, including

• advantages of using immobilized enzymes is the easy recovery of the enzyme at the end of the reaction by simple filtration and its reuse in successive reactions. As previously indicated, in the transamination reaction it is necessary to use DMSO as a co-solvent to solubilize the substrate 1, which is

Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review

• Fabio Tonin and
• Isabel W. C. E. Arends

Beilstein J. Org. Chem. 2018, 14, 470–483, doi:10.3762/bjoc.14.33

• immobilization of enzymes [93]. The first system shows high stability (enzymes in the membrane reactor have a half-life of 1–2 weeks) and the biocatalysts can be reused for eight cycles of conversions. On the other hand, immobilized enzymes show a higher productivity (88.5 vs 8 g L−1 d−1) despite the fact that

• the half-life (23 h) is lower and the biocatalyst can be reused for only five cycles of conversions. In order to reduce the mechanical stress that might inactivate the immobilized enzymes, the flow-system represents a valid technology. The packed-bed reactor set up by Zheng et al. partially solved

• an immobilized NAD+-dependent 7α-HSHS (first reactor column); afterwards, 7-oxo-LCA is reduced to UDCA by an immobilized NADP+-dependent 7β-HSDH (second reactor column). The cofactors are individually regenerated in each column by the co-immobilized enzymes, lactate dehydrogenase (LDH) and glucose

Highly stable and reusable immobilized formate dehydrogenases: Promising biocatalysts for in situ regeneration of NADH

• Barış Binay,
• Dilek Alagöz,
• Deniz Yildirim,
• Ayhan Çelik and
• S. Seyhan Tükel

Beilstein J. Org. Chem. 2016, 12, 271–277, doi:10.3762/bjoc.12.29

• and then C. boidinii FDH was immobilized onto it. It is generally expected from the covalently immobilized enzymes that they should be more durable against temperature inactivation than their free forms. As shown in Figure 4, the free FDH completely lost its initial activity at 35 °C after 24 h

Biosynthesis of rare hexoses using microorganisms and related enzymes

• Zijie Li,
• Yahui Gao,
• Hideki Nakanishi,
• Xiaodong Gao and
• Li Cai

Beilstein J. Org. Chem. 2013, 9, 2434–2445, doi:10.3762/bjoc.9.281

• has the advantages of using cheaper catalysts without purification and the avoidance of cofactor recycling in vitro, while enzymatic conversion is more controllable and scalable. In addition, immobilized enzymes offer advantages over free and soluble enzymes in many aspects: 1) immobilized enzymes can

Flow synthesis of phenylserine using threonine aldolase immobilized on Eupergit support

• Jagdish D. Tibhe,
• Hui Fu,
• Timothy Noël,
• Qi Wang,
• Jan Meuldijk and
• Volker Hessel

Beilstein J. Org. Chem. 2013, 9, 2168–2179, doi:10.3762/bjoc.9.254

• temperature. Effect of flow rates on yield for immobilized enzymes in a packed bed microreactor (70 °C). Reaction conditions: Reaction volume (0.250 mL), TA (1.1 mg, specific activity – 0.052 U/mg), temperature (70 °C). Effect of residence time on yield for free enzymes in a Teflon tube microreactor at 70 °C

Chemoenzymatic synthesis and biological evaluation of enantiomerically enriched 1-(β-hydroxypropyl)imidazolium- and triazolium-based ionic liquids

• Paweł Borowiecki,
• Małgorzata Milner-Krawczyk and
• Jan Plenkiewicz

Beilstein J. Org. Chem. 2013, 9, 516–525, doi:10.3762/bjoc.9.56

• ) and two immobilized enzymes (Novozym SP 435, Amano PS-IM), were chosen for the transesterification studies. The screenings were performed with a 5-fold molar excess of vinyl acetate as an irreversible acyl donor at ambient temperature. The selection of a proper solvent is a significant factor in

Coupled chemo(enzymatic) reactions in continuous flow

• Ruslan Yuryev,
• Simon Strompen and
• Andreas Liese

Beilstein J. Org. Chem. 2011, 7, 1449–1467, doi:10.3762/bjoc.7.169

• reactor could be operated in continuous mode as well, if the immobilized enzymes were more active and stable enough. 2. Cascade-reactor processes in vitro The drawbacks of single-reactor coupled-reaction enzymatic processes arising from incompatibility of individual reaction steps may be overcome in

• peroxidase. All reactions are carried out in an aqueous microfluidic system consisting of a cascade of three microreactors separately loaded with zinc powder and immobilized enzymes. The observed low conversion of 19% and space-time yield of 4 g L−1 day−1 imply the need for optimization, but demonstrate the

• -ribulose 1,5-bisphosphate (58) in a series of eleven packed-bed reactors containing immobilized enzymes (Scheme 17) [41]. The aim of the process is to continuously regenerate D-58, which is used as an acceptor for the biocatalytic fixation of CO2 resulting in the formation of two molecules of D-57. The

N-acylation of ethanolamine using lipase: a chemoselective catalyst

• Mazaahir Kidwai,
• Roona Poddar and
• Poonam Mothsra

Beilstein J. Org. Chem. 2009, 5, No. 10, doi:10.3762/bjoc.5.10

• proportions of the substrate ratio. Conventional versus microwave irradiation Enzymatic reaction was performed under conventional heating as well as in the presence of microwave irradiation. Considering that immobilized enzymes are highly thermo stable, it is natural that microwave-assistance should also be

Towards practical biocatalytic Baeyer- Villiger reactions: applying a thermostable enzyme in the gram- scale synthesis of optically- active lactones in a two-liquid- phase system

• Frank Schulz,
• François Leca,
• Frank Hollmann and
• Manfred T. Reetz

Beilstein J. Org. Chem. 2005, 1, No. 10, doi:10.1186/1860-5397-1-10

• related systems and is especially not possible when using immobilized enzymes, a standard method for stabilizing them. We view this study as a crucial step towards practical BVMOs, because PAMO, the P1-P3 mutants and presumably future PAMO-variants can now be used in a simple preparative scale procedure