Lipase Catalyzed Regioselective Lactamization as a Key Step in the Synthesis of <i>N</i>-Boc (2<i>R</i>)-1,4-Oxazepane-2-Carboxylic Acid

Aurell, Carl‐Johan; Karlsson, Staffan; Pontén, Fritiof; Andersen, Sebastian

doi:10.1021/op5001644

Cited by 10 publications

(9 citation statements)

References 6 publications

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“…The recovery of the freely suspended biocatalyst particles can be challenging, requiring filtration or centrifugation [279]. The biocatalyst recovery can be simplified using a basket-rotating bed reactor (RBR), which enables simultaneous mixing and effective percolation of liquid through the bed of the catalyst packed in a cylindrical basket, thus avoiding the catalysts destruction, enhancing mass transport, and facilitating separation of the catalyst [280,281,282]. However, the size of the applied catalyst particles/enzyme carriers needs to be larger than 0.1–0.2 mm [280,281].…”

Section: Reactor Engineering For (Non)-leloir Glycosyltransferasesmentioning

confidence: 99%

“…The biocatalyst recovery can be simplified using a basket-rotating bed reactor (RBR), which enables simultaneous mixing and effective percolation of liquid through the bed of the catalyst packed in a cylindrical basket, thus avoiding the catalysts destruction, enhancing mass transport, and facilitating separation of the catalyst [280,281,282]. However, the size of the applied catalyst particles/enzyme carriers needs to be larger than 0.1–0.2 mm [280,281]. The scale-up of RBRs is challenging due to the large size of the rotor as well as the power required for rotating, although a 750-L scale has been successfully demonstrated (Chiralvision.…”

Section: Reactor Engineering For (Non)-leloir Glycosyltransferasesmentioning

confidence: 99%

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Leloir Glycosyltransferases in Applied Biocatalysis: A Multidisciplinary Approach

Mestrom

Przypis

Kowalczykiewicz

et al. 2019

IJMS

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Enzymes are nature's catalyst of choice for the highly selective and efficient coupling of carbohydrates. Enzymatic sugar coupling is a competitive technology for industrial glycosylation reactions, since chemical synthetic routes require extensive use of laborious protection group manipulations and often lack regio-and stereoselectivity. The application of Leloir glycosyltransferases has received considerable attention in recent years and offers excellent control over the reactivity and selectivity of glycosylation reactions with unprotected carbohydrates, paving the way for previously inaccessible synthetic routes. The development of nucleotide recycling cascades has allowed for the efficient production and reuse of nucleotide sugar donors in robust one-pot multi-enzyme glycosylation cascades. In this way, large glycans and glycoconjugates with complex stereochemistry can be constructed. With recent advances, LeLoir glycosyltransferases are close to being applied industrially in multi-enzyme, programmable cascade glycosylations.hydroxynitrile lyases catalyzed the enzymatic hydrolysis of the glycoside amygdalin [3]. Moving almost two centuries forward, the largest volumetric biocatalytic industrial process is the application of glucose isomerase for the production of high fructose syrup for food and drink applications, producing fructose from glucose at 10 7 tons per year [4]. The secret of the success of enzymes in the production or treatment of carbohydrates and glycosides is their exquisite stereo-and regioselectivity. The excellent selectivity of enzymes is required due to the diversity of structural features of carbohydrates [5], comprising d-and l-epimers, ring size, anomeric configuration, linkages, branching, and oxidation state(s). Since drug targets often exhibit specificity for all of these structural features, the production process should not contain any side-products to prevent undesired side-effects [6].The challenge in the synthesis of carbohydrates is their wide variety of functionalities and stereochemistry ( Figure 1). (Poly)hydroxyaldehydes containing a terminal aldehyde are referred to as aldoses and (poly)hydroxyketones are defined as ketoses. In aqueous solutions, monosaccharides form equilibrium mixtures of linear open-chain and ring-closed 5-or 6-membered furanoses or pyranoses, respectively. For aldoses, the asymmetric ring forms at C-1. For ketoses, it closes at C-2 as an axial (α) or equatorial (β) hemiacetal or hemiketal, respectively (commonly defined as the anomeric center). A glycosidic linkage is a covalent O-, S-, N-, or C-bond connecting a monosaccharide to another residue resulting in a glycoside, while glucoside is specific for a glucose moiety. The equatorial or axial position of the glycosidic bond is referred to as α-(axial) or β-linkage (equatorial). The number of carbohydrates linked via glycosidic bonds can be subdivided into oligosaccharides with two to ten linked carbohydrates, while polysaccharides (glycans) contain more than ten glycosidic bonds. A glycan either con...

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Section: Reactor Engineering For (Non)-leloir Glycosyltransferasesmentioning

confidence: 99%

Section: Reactor Engineering For (Non)-leloir Glycosyltransferasesmentioning

confidence: 99%

Leloir Glycosyltransferases in Applied Biocatalysis: A Multidisciplinary Approach

Mestrom

Przypis

Kowalczykiewicz

et al. 2019

IJMS

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“…But the latter implies the need for a high backpressure, and hence endangers safety. A rational engineering solution may be the use of rotating bed reactors (RBRs), that allow for a simultaneous mixing and percolation of reactants through the bed of heterogeneous catalysts placed in a cylindrical basket, mounted at the end of the shaft (Aurell, Karlsson, Ponten, & Andersen, 2014;Mallin, Muschiol, Byström & Bornscheuer, 2013;Szymańska, Odrozek, Zniszczo l, Pud lo & Jarze˛bski, 2017). The problems of catalysts damage and separation are removed, and the tortuous interconnected channels between the particles can induce intensive lateral mixing and much enhanced mass transfer, which boost the overall reaction rate (Xu et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, similarly as in PBRs the catalysts load can be high, and it translates into high values of STY, without compromising process safety. For these reasons, the RBRs attract increasing attention and were recently applied in a number of practical situations: hydrogenation of D-xylose to D-xylitol, using ruthenium decorated carbon foam (Pham et al, 2016), lipase catalyzed regioselective lactamization (Aurell, Karlsson, Ponten, & Andersen, 2014), selective fractionation of hemicellulose and lignin (Eta, Anugwom, Virtanen, Maki-Arvela & Mikkola, 2014) or hardwood (Eta & Mikkola, 2016), and (S)-naproxen synthesis using immobilized decarboxylase (Aβmann et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…A limitation for the RBR application is posed by the size of catalyst particles -it needs to be larger than ca. 0.4 mm (Aurell, Karlsson, Ponten, & Andersen, 2014;Mallin, Muschiol, Byström & Bornscheuer, 2013;Szymańska, Odrozek, Zniszczo l, Pud lo & Jarzebski, 2017), and this eliminates the use of the most common mesoporous silica materials as enzyme supports, but N435 meets this condition. A rational option for the RBR application may be the use of silica beads/pellets which possess an open, optimally hierarchical meso-macropore structure, that is stable in various solvents, can easily be functionalized to attach enzymes and allow for an unhindered transport of reactants to the catalytic sites.…”

Section: Introductionmentioning

confidence: 99%

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Rotating bed reactor packed with heterofunctional structured silica-supported lipase or Novozym 435. Developing an effective system for the organic solvent and aqueous phase reactions

Szymańska¹,

Kowalczykiewicz²,

Gillner³

et al. 2020

Preprint

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Production of specialty chemicals increasingly makes use of enzyme catalysts, and Novozym 435 (N435) is among most often applied. However, its polymeric skeleton is unstable in many solvents. In this context, we report results of a systematic study of the biocatalysts, fabricated using highly porous siliceous pellets/enzyme (MH), grafted with octyl (-O), amino (-A) and octyl and amino (-OA) groups, deployed in a rotating bed reactor and tested in hydrolysis and esterification reactions. N435 appeared the most active in both reactions, when activity was related to the catalyst's mass, mainly owing to very large enzyme load. But its structure degraded in many typical solvents, whereas no such effect was detected in MH-O-and MH-OA-catalysts. MH-O showed the highest specific activity, however, a significant enzyme leaching was observed in a hydrolytic reaction, in contrast to MH-OA. In esterification reaction the MH-O-bound lipase was not only most active but also quite stable.

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Conversion of γ‐ and δ‐Keto Esters into Optically Active Lactams. Transaminases in Cascade Processes

et al. 2017

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A one-pot two-step enzymatic strategy has been designed for the production of optically active gand d-lactams in aqueous medium under mild conditions. The approach is based on the biotransamination of ethyl or methyl keto esters bearing different alkyl or aryl substitution patterns at a-position to the ketone functionality. In this manner, the keto esters were transformed into the corresponding amino esters with excellent conversions, which underwent spontaneous cyclisation in the reaction medium without addition of external reagents. Depending on the transaminase selectivity, both lactam enantiomers can be obtained, so initial enzyme screenings were performed using commercially available and made in house enzymes. Reaction conditions were optimised focusing on the substrate concentration, temperature and ratio of amine donor vs acceptor. Thus, ten g-and d-lactams were obtained in good to high isolated yields (70-90%) and excellent selectivities (94-99%) after one or two days at 30 or 45 8C.

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Lipase Catalyzed Regioselective Lactamization as a Key Step in the Synthesis of N-Boc (2R)-1,4-Oxazepane-2-Carboxylic Acid

Cited by 10 publications

References 6 publications

Leloir Glycosyltransferases in Applied Biocatalysis: A Multidisciplinary Approach

Leloir Glycosyltransferases in Applied Biocatalysis: A Multidisciplinary Approach

Rotating bed reactor packed with heterofunctional structured silica-supported lipase or Novozym 435. Developing an effective system for the organic solvent and aqueous phase reactions

Conversion of γ‐ and δ‐Keto Esters into Optically Active Lactams. Transaminases in Cascade Processes

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