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Item type:Publication, Access status: with files , Überwindung der Limitierungen von L- Threoninaldolasen in der Biokatalyse: durch Reaktionstechnik zu hocheffizienten Anwendungen(2025-06-30); Threonine aldolases (LTA) have been demonstrated to be a synthetically valuable enzyme class for performing diastereoselective C-C forming reactions. Such biotransformations are of interest for the preparation of pharmaceuticals and fine chemicals as they catalyze asymmetric aldol reactions with glycine as readily available aldol donor, thus resulting in the formation of α-amino-β-hydroxycarboxylic acids. So far, a major limitation has been the non-favourable diastereoselectivity due to the switch from a kinetic to thermodynamic control of the biocatalytic reaction system. This project aimed for understanding and overcoming such process limitations.Publicationtype: Report19 9 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: with files , Benchtop NMR-Based In-Line Analysis of Diastereoselective Enzymatic α-Amino Acid Synthesis: Quantification and Validation(American Chemical Society (ACS), 2024-10-18); ; ; ; This study investigates the application of a commercial low-field benchtop NMR for real-time monitoring of enzymatically catalyzed reactions, focusing on the diastereoselectivity of the threonine aldolase-catalyzed stereoselective aldol reaction between glycine and benzaldehyde. Despite the signal overlap inherent in the weak electromagnetic field of the benchtop NMR system, a complemental hard modeling (CHM) approach effectively differentiates between diastereomers, enabling the determination of enzymatic diastereoselectivity and the transition from kinetic to thermodynamic control. In particular, the achievement of thermodynamic equilibrium in the enzymatic aldol reaction is observed for the first time using in-line methods, occurring at 30% benzaldehyde conversion after 2 h. In-line NMR analysis reveals a diastereomeric excess of 37:63 (erythro/threo), which closely aligns with off-line measurements via GC and HPLC (36:64). This determination of diastereomers using CHM enhances the efficiency of in-line monitoring in enzymatic reactions, promising significant advancements in pharmaceutical process development. Overall, the study underscores the utility of benchtop NMR systems for in-line analysis of enzymatic reactions, offering insights into reaction mechanisms, selectivity, and equilibrium dynamics, thereby facilitating more efficient process optimization in the area of fine chemicals.Publicationtype: Journal Article24 8 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: with files , Structure-performance guided design of sustainable plasticizers from biorenewable feedstocksThe search for more sustainable solutions for plastics production, moving away from petrochemical feedstocks as today's major raw material basis, is a research area of increasing interest. This task goes far beyond the issue of designing greener polymers and their related monomers as tailor-made plastics require, besides the polymer itself, further components. These additives also need to be switched from typically fossil-based to bio-renewable raw materials. One of such necessary components for many applications are plasticizers, and a major application of them is related to polyvinyl chloride (PVC) as one of the leading polymers with a wide range of applications. Typically today‘s plasticizers are based on fossil feedstocks, and some of them such as specific ortho-phthalates as the most important product class of plasticizers are now subject to restrictions and authorization by the EU's REACH legislation due to their toxicological profile. In this contribution, we report the synthesis and technical evaluation of alternative, novel bicyclic plasticizer candidates, which are fully accessible from renewable feedstocks. In detail, these new plasticizer target molecules are based on the use of the furan-derivative 2-methylfuran, maleic anhydride and 2-ethylhexanol as bio-based starting materials. The synthetic concept consists of an initial Diels-Alder reaction with 2-methylfuran and a subsequent hydrogenation and optional esterification step. The applied reactions are well-known as economic and sustainable technologies. Thus, not only the starting materials (being of bio-based origin) but also the selected reaction technologies for the syntheses of the target molecules are sustainable. Furthermore, a range of performance tests enabled an insight into structure-performance relationships and revealed promising plasticizing properties of this new bio-based plasticizer generation with, e. g., an attractive solution temperature fulfilling the criterium for a “fast fuser” as well as good compatibility with PVC.Publicationtype: Journal ArticleScopus© Citations 4 71 278 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Towards bio-based plasticizers with reduced toxicity: Synthesis and performance testing of a 3-methylphthalate(2020-12); ; ; ; As a very durable material, soft polyvinyl chloride (PVC) is used for many applications in the field of consumer products. To enable the desired properties, for example for medical devices, the addition of plasticizers is required. For this purpose, mostly dialkyl phthalates are used being produced on a multi-million tons scale annually. Since some of these are associated with human health effects, there is an increasing demand for the search of alternatives. Besides reduced toxicity while maintaining excellent performance features, an economic access as well as biorenewable starting materials are further criteria, which should be ideally fulfilled by such a new plasticizer generation. Targeting these demands and in contrast to most available substitutes being based on petrochemical feedstock, we developed a synthetic route starting from bio-renewable platform chemicals. In detail, a Diels-Alder reaction of 2-methylfuran and maleic anhydride and subsequent dehydration leads to three phthalate derivatives with different alcohol components bearing a methyl group at the aromatic ring. As a representative substance, di(2-ethylhexyl) 3-methylphthalate was chosen for performance tests, and this new bio-based alternative offers properties similar to known plasticizers in such initial studies.Publicationtype: Journal Article159 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Fatty alcohol synthesis from fatty acids at mild temperature by subsequent enzymatic esterification and metal-catalyzed hydrogenation(2020-10-14); ; ; ; Fatty alcohols are important products in chemical industry to be used in the formulation of surfactants and lubricants. This work describes a two step approach for the production of myristyl alcohol under neat conditions by combining a lipase catalyzed esterification of myristic acid and myristyl alcohol with a ruthenium catalyzed hydrogenation of the intermediate myristyl myristate. The esterification was carried out in a bubble column reactor with the commercial immobilized lipase B from Candida antarctica as a biocatalyst, while the hydrogenation was conducted under pressurized conditions being catalyzed by the homogeneous chemocatalyst Ru-Macho-BH. By investigating the reaction steps separately, comparable reaction rates were found for the esterification of short chain and long chain alcohols. Additionally, the hydrogen pressure could be reduced to 35 bar compared to the current industrial Lurgi process. Characterization of cross interactions by the reactants myristic acid and sodium myristate in the hydrogenation demonstrates that the metal catalyst was completely deactivated, even at a low amount of 0.5 mol% of myristic acid. Complete conversion of myristic acid in the esterification with equal amounts of myristic acid and myristyl alcohol was obtained, overcoming any limitation in the hydrogenation. In comparison to the Lurgi process starting also from fatty acid and fatty alcohols, the chemoenzymatic two step reaction sequence could be realized at lower reaction temperatures of 60 and 100 °C as well as lower hydrogen pressures of 35 bar.Publicationtype: Journal ArticleScopus© Citations 2 103 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , FTIR based kinetic characterisation of an acid-catalysed esterification of 3-methylphthalic anhydride and 2-ethylhexanol(2020-06-28); ; ; ; In this study, an inline analytical method was designed and applied in process characterisation and development. The model reaction is the two-step diesterification of 3-methylphthalic anhydride with 2-ethylhexanol consisting of alcoholysis as the first step, followed by an acid-catalysed, second esterification step leading to the corresponding diester. The final product is a potential, alternative plasticiser. For the inline measurements, attenuated total reflection Fourier transformed infrared spectroscopy (ATR-FTIR) was implemented. In order to evaluate the spectra recorded during the reaction, a chemometric model was established. In this work, Indirect Hard Modeling (IHM), a non-linear modeling approach was employed. The respective model was calibrated by using offline samples analysed with gas (GC) and liquid chromatography (HPLC). After successful validation of the chemometric model, the inline measurements were utilized for reaction characterisation. The acid-catalysed, second esterification step was identified as the limiting reaction step. From batch reactions conducted at different temperatures, the energy of activation of this step was determined to be 79.5 kJ mol-1. Additionally, kinetics were shown to follow a pseudo-first order with respect to the monoester formation and a kinetic model was established. The model was validated in simulations with changed reaction conditions.Publicationtype: Journal Article113 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Kinetic insights into ϵ-caprolactone synthesis: Improvement of an enzymatic cascade reaction(Wiley, 2017-02-23); ; ; ; A computational approach for the simulation and prediction of a linear three-step enzymatic cascade for the synthesis of ϵ-caprolactone (ECL) coupling an alcohol dehydrogenase (ADH), a cyclohexanone monooxygenase (CHMO), and a lipase for the subsequent hydrolysis of ECL to 6-hydroxyhexanoic acid (6-HHA). A kinetic model was developed with an accuracy of prediction for a fed-batch mode of 37% for substrate cyclohexanol (CHL), 90% for ECL, and >99% for the final product 6-HHA. Due to a severe inhibition of the CHMO by CHL, a batch synthesis was shown to be less efficient than a fed-batch approach. In the fed-batch synthesis, full conversion of 100 mM CHL was 28% faster with an analytical yield of 98% compared to 49% in case of the batch synthesis. The lipase-catalyzed hydrolysis of ECL to 6-HHA circumvents the inhibition of the CHMO by ECL enabling a 24% higher product concentration of 6-HHA compared to ECL in case of the fed-batch synthesis without lipase. Biotechnol. Bioeng. 2017;114: 1215–1221. © 2017 Wiley Periodicals, Inc.Publicationtype: Journal Article117 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Enzymatic resolution of an amine under solvent-free conditions with diethyl malonate as reagent for acylationThe extension of the enzymatic resolution of amines catalyzed by an immobilized lipase in combination with diethyl malonate as acyl donor towards a solvent-free process is described. In such a resolution process the resulting chiral amide was formed with both high conversion and enantioselectivity, and this solvent-free synthetic method turned out to be robust and efficient also at an elevated 50 mmol-scale reaction, leading to the desired amide with 50% conversion, in 43.5% yield and with excellent enantiomeric excess of 99% ee. This method proceeding at a short reaction time (4.5 h) opens up a perspective for future development towards a large-scale feasible process technology for the enantioselective synthesis of chiral amines.Publicationtype: Journal Article123 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , An alternative approach towards poly-ε-caprolactone through a chemoenzymatic synthesis: combined hydrogenation, bio-oxidations and polymerization without the isolation of intermediates(Royal Society of Chemistry (RSC), 2017-01-06); ; ; ; A novel synthetic route towards the polymer poly-ε-caprolactone based on a chemoenzymatic reaction sequence was developed. Initial hydrogenation of phenol to cyclohexanol gave a crude product, which was directly used without work-up for a subsequent biocatalytic double oxidation towards ε-caprolactone by means of an alcohol dehydrogenase and a monooxygenase. In order to overcome product inhibition effects, an in situ-product removal strategy via extraction of ε-caprolactone from an aqueous reaction medium with an organic solvent in the presence of a permeable polydimethylsiloxane membrane was applied. Furthermore, this in situ-product removal was combined with lipase-catalyzed polymerization in the organic phase at 25 °C. The obtained crude product contained a polymer fraction with a degree of polymerization comparable to commercial poly-ε-caprolactone.Publicationtype: Journal Article99 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , A Fed-Batch Synthetic Strategy for a Three-Step Enzymatic Synthesis of Poly-ϵ-caprolactone(2016-11-22); ; ; ; A three-step enzymatic reaction sequence for the synthesis of poly-ϵ-caprolactone (PCL) was designed running in a fed-batch operation. The first part of the cascade consisted of two oxidation steps starting with alcohol dehydrogenase catalyzed oxidation from cyclohexanol to cyclohexanone and further oxidation to ϵ-caprolactone (ECL) by means of a Baeyer–Villiger monooxygenase. As a third step, lipase-catalyzed hydrolysis of the lactone to 6-hydroxyhexanoic acid (6-HHA) was designed. With this biocatalytic multistep process reported herein, severe substrate surplus and product inhibition could be circumvented by the fed-batch operation by adding the cyclohexanol substrate and by in situ product removal of ECL by hydrolysis, respectively. Up to 283 mm product concentration of 6-HHA was reached in the fed-batch operated process without loss in productivity within 20 h. After extraction and subsequent polymerization catalyzed by Candida antarctica lipase B, analysis of the unfractionated polymer revealed a bimodal distribution of the polymer population, which reached a mass average molar mass (Mw) value of approximately 63 000 g mol−1 and a dispersity (Mw/Mn) of 1.1 for the higher molecular weight population, which thus revealed an alternative route to the conventional synthesis of PCL.Publicationtype: Journal Article69