Chemoenzymatische Mehrstufen-Prozesse zur enantioselektiven Synthese chiraler Alkohole

Heidlindemann M. Chemoenzymatische Mehrstufen-Prozesse zur enantioselektiven Synthese chiraler Alkohole. Bielefeld: Universitätsbibliothek Bielefeld; 2014

Combination of Asymmetric Organo- and Biocatalytic Reactions in Organic Media Using Immobilized Catalysts in Different Compartments

Heidlindemann M, Rulli G, Berkessel A, Hummel W, Gröger H. Combination of Asymmetric Organo- and Biocatalytic Reactions in Organic Media Using Immobilized Catalysts in Different Compartments. ACS Catalysis. 2014;4(4):1099-1103.A proof of concept for the combination of an asymmetric organocatalytic reaction with a biotransformation toward a "one-pot like" process for 1,3-diols based on immobilized organo- and biocatalysts, which are utilized in different compartments, is demonstrated. This process which runs completely in organic media consists of an initial proline-derivative-catalyzed aldol reaction and a subsequent reduction of the aldol adduct catalyzed by an alcohol dehydrogenase (ADH) without the need for intermediate isolation. Economically attractive superabsorber-based coimmobilization for the ADH and its cofactor NAD(+) turned out to give a highly efficient biocatalyst with excellent reusability and simple product separation from the immobilizate under avoidance of any tedious extraction steps during the overall process

Towards catalyst compartimentation in combined chemo- and biocatalytic processes: Immobilization of alcohol dehydrogenases for the diastereoselective reduction of a β-hydroxy ketone obtained from an organocatalytic aldol reaction

Rulli G, Heidlindemann M, Berkessel A, Hummel W, Gröger H. Towards catalyst compartimentation in combined chemo- and biocatalytic processes: Immobilization of alcohol dehydrogenases for the diastereoselective reduction of a β-hydroxy ketone obtained from an organocatalytic aldol reaction. Journal of biotechnology. 2013;168(3):271-276.The alcohol dehydrogenases (ADHs) from Lactobacillus kefir and Rhodococcus sp., which earlier turned out to be suitable for a chemoenzymatic one-pot synthesis with organocatalysts, were immobilized with their cofactors on a commercially available superabsorber based on a literature known protocol. The use of the immobilized ADH from L. kefir in the reduction of acetophenone as a model substrate led to high conversion (>95%) in the first reaction cycle, followed by a slight decrease of conversion in the second reaction cycle. A comparable result was obtained when no cofactor was added although a water rich reaction media was used. The immobilized ADHs also turned out to be suitable catalysts for the diastereoselective reduction of an organocatalytically prepared enantiomerically enriched aldol adduct, leading to high conversion, diastereomeric ratio and enantioselectivity for the resulting 1,3-diols. However, at a lower catalyst and cofactor amount being still sufficient for biotransformations with "free" enzymes the immobilized ADH only showed high conversion and >99% ee for the first reaction cycle whereas a strong decrease of conversion was observed already in the second reaction cycle, thus indicating a significant leaching effect of catalyst and/or cofactor

Chemoenzymatic Synthesis of Vitamin B5-Intermediate (R)-Pantolactone via Combined Asymmetric Organo- and Biocatalysis

Heidlindemann M, Hammel M, Scheffler U, et al. Chemoenzymatic Synthesis of Vitamin B5-Intermediate (R)-Pantolactone via Combined Asymmetric Organo- and Biocatalysis. The Journal of Organic Chemistry. 2015;80(7):3387-3396.The combination of an asymmetric organocatalytic aldol reaction with a subsequent biotransformation toward a "one-pot-like" process for the synthesis of (R)-pantolactone, which to date is industrially produced by a resolution process, is demonstrated. This process consists of an initial aldol reaction catalyzed by readily available l-histidine followed by biotransformation of the aldol adduct by an alcohol dehydrogenase without the need for intermediate isolation. Employing the industrially attractive starting material isobutanal, a chemoenzymatic three-step process without intermediate purification is established allowing the synthesis of (R)-pantolactone in an overall yield of 55% (three steps) and high enantiomeric excess of 95%

Combination of Asymmetric Organo- and Biocatalytic Reactions in Organic Media Using Immobilized Catalysts in Different Compartments

A proof of concept for the combination of an asymmetric organocatalytic reaction with a biotransformation toward a “one-pot like” process for 1,3-diols based on immobilized organo- and biocatalysts, which are utilized in different compartments, is demonstrated. This process which runs completely in organic media consists of an initial proline-derivative-catalyzed aldol reaction and a subsequent reduction of the aldol adduct catalyzed by an alcohol dehydrogenase (ADH) without the need for intermediate isolation. Economically attractive superabsorber-based coimmobilization for the ADH and its cofactor NAD⁺ turned out to give a highly efficient biocatalyst with excellent reusability and simple product separation from the immobilizate under avoidance of any tedious extraction steps during the overall process

Chemoenzymatic Synthesis of Vitamin B5-Intermediate (<i>R</i>)‑Pantolactone via Combined Asymmetric Organo- and Biocatalysis

The combination of an asymmetric organocatalytic aldol reaction with a subsequent biotransformation toward a “one-pot-like” process for the synthesis of (<i>R</i>)-pantolactone, which to date is industrially produced by a resolution process, is demonstrated. This process consists of an initial aldol reaction catalyzed by readily available l-histidine followed by biotransformation of the aldol adduct by an alcohol dehydrogenase without the need for intermediate isolation. Employing the industrially attractive starting material isobutanal, a chemoenzymatic three-step process without intermediate purification is established allowing the synthesis of (<i>R</i>)-pantolactone in an overall yield of 55% (three steps) and high enantiomeric excess of 95%

First Tandem-Type One-Pot Process Combining Asymmetric Organo- and Biocatalytic Reactions in Aqueous Media Exemplified for the Enantioselective and Diastereoselective Synthesis of 1,3-Diols

Rulli G, Duangdee N, Hummel W, Berkessel A, Gröger H. First Tandem-Type One-Pot Process Combining Asymmetric Organo- and Biocatalytic Reactions in Aqueous Media Exemplified for the Enantioselective and Diastereoselective Synthesis of 1,3-Diols. EUROPEAN JOURNAL OF ORGANIC CHEMISTRY. 2017;2017(4):812-817.A suitable "process window" was identified for the combination of an asymmetric organocatalytic aldol reaction and subsequent biocatalytic reduction in aqueous medium, which thus enabled the enantio- and diastereoselective synthesis of 1,3-diols in a tandem-type, one-pot process. A key feature of this one-pot synthesis is the high 500 mM loading of the aldehyde substrate used as a starting material