Deracemisation of Mandelic Acid to Optically Pure Non‐Natural <scp>L</scp>‐Phenylglycine <i>via</i> a Redox‐Neutral Biocatalytic Cascade

Resch, Verena; Fabian, Walter M. F.; Kroutil, Wolfgang

doi:10.1002/adsc.200900891

Cited by 94 publications

(51 citation statements)

References 35 publications

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“…For ammonium chloride buffers, pH values <8.5 cannot be attained and hence ammonium formate buffer was investigated at various pH values (28). At pH 8 to 8.5, the amination of (R)-1a (20 mM) was achieved in 93% conversion and >99% ee ( The hydrogen-borrowing cascade was initially tested on a limited number of 1-phenyl-2-propanol derivatives 1a-1e (Table 1) for amination with inversion of configuration (entries 1-5), retention of configuration (entries [15][16][17][18][19] and asymmetric amination of racemic alcohols (entry 29-33). Conversion varied from moderate to excellent, whereas the ee was excellent in almost all cases.…”

Section: Europe Pmc Funders Author Manuscriptsmentioning

confidence: 99%

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Conversion of alcohols to enantiopure amines through dual-enzyme hydrogen-borrowing cascades

Mutti

Knaus

Scrutton

et al. 2015

Science

376

277

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Abstractα-Chiral amines are key intermediates for the synthesis of a plethora of chemical compounds on industrial scale. Here we present a biocatalytic hydrogen-borrowing amination of primary and secondary alcohols that allows for the efficient and environmentally benign production of enantiopure amines. The method relies on the combination of an alcohol dehydrogenase (ADHs from Aromatoleum sp., Lactobacillus sp. and Bacillus sp.) enzyme operating in tandem with an amine dehydrogenase (AmDHs engineered from Bacillus sp.) to aminate a structurally diverse range of aromatic and aliphatic alcohols (up to 96% conversion and 99% enantiomeric excess). Furthermore, primary alcohols are aminated with high conversion (up to 99%). This redox selfsufficient network possesses high atom efficiency, sourcing nitrogen from ammonium and generating water as the sole by-product.Amines are amongst the most frequently used chemical intermediates for the production of APIs (active pharmaceutical ingredients), fine chemicals, agrochemicals, polymers, dyestuffs, pigments, emulsifiers and plasticizing agents (1). However, the requisite amines are scarce in nature and their industrial production mainly relies upon the metal-catalysed hydrogenation of enamides (i.e. obtained from related ketone precursors), a process requiring transition metal complexes, which are expensive and increasingly unsustainable (2). Moreover, the asymmetric synthesis of amines from ketone precursors requires protection and deprotection steps that generate copious amounts of waste. As a consequence, various chemical processes for the direct conversion of alcohols into amines have been developed during the last decade. The intrinsic advantage of the direct amination of an Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts alcohol is that the reagent and the product are in the same oxidation state and therefore, theoretically, additional redox equivalents are not required.However, many of these methods have low efficiency and high environmental impact (e.g. Mitsunobu reaction) (3). The amination of simple alcohols such as methanol and ethanol, via heterogeneous catalysis, requires harsh conditions (>200 °C) and more structurally diverse alcohols are either converted with extremely low chemoselectivity or not converted at all (4). Furthermore, most of the work in this field involves non-chiral substrates whereas 40% of the commercial optically active drugs are chiral amines (2). Increasingly, biocatalytic methods are applied for the production of optically active amines, e.g. the lipase catalysed resolution of racemic mixtures of amines or the ω-transaminase process with a most recent example employing an engineered enzyme applied to the industrial manufacture of the diabetes medication Januvia® (sitagliptin) (5,6,7).Multi-step chemical reactions in one pot avoid the need for isolation of intermediates and purification steps. This approach leads to economic as well as environmental benefits since time-consuming intermediate work-ups are not...

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Section: Europe Pmc Funders Author Manuscriptsmentioning

confidence: 99%

“…Another redox neutral biocatalytic cascade was applied for the deracemisation of mandelic acid to enantioenriched L-phenylglycine. However, the method was limited to the conversion of this specific α-hydroxy acid (17).…”

mentioning

confidence: 99%

Conversion of alcohols to enantiopure amines through dual-enzyme hydrogen-borrowing cascades

Mutti

Knaus

Scrutton

et al. 2015

Science

376

277

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“…It is worth mentioning the work developed by Kroutil and co-workers in the field of the deracemization of sec-alcohols by using two enantiocomplementary ADHs with two independent cofactor-recycling systems, [65] or the deracemization of rac-mandelic acid into L-phenylglycine via a redox-neutral biocatalytic cascade using D-mandelate dehydrogenase and an L-amino acid dehydrogenase, internally recycling NADH due to the action of both processes. [66] In these cases, the concurrent oxidative and reductive half-reactions allowed to obtain the final enantiopure product in quantitative yield.…”

Section: Methodsmentioning

confidence: 99%

Recent Advances in Cofactor Regeneration Systems Applied to Biocatalyzed Oxidative Processes

Rodrı́guez¹,

Lavandera²,

Gotor

2012

COC

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Abstract. Nowadays, the design of sustainable processes applicable at industrial scale is highly desirable due to environmental reasons. The use of biocatalytic reactions to carry out oxidative transformations is one of the possible strategies framed in here due to the mildness and usually high selectivities achieved with these methods. Anyway, while implementing this type of system at industrial scale several drawbacks must be overcome in order to obtain efficient setups. Historically, one of the main issues has been the cofactor-dependency of these biocatalysts to be active. Herein, we will show the state-of-the-art concerning the recent efforts developed in the design of (potentially) efficient methods to regenerate the cofactor in oxidative transformations. Thus, the more studied enzymatic methods will be discussed to highlight some recent examples dealing with the co-expression of both oxidative and recycling enzymes in one host or the development of self-sufficient biocatalysts. Furthermore, novel applications of these systems to couple two productive synthetic reactions will also be reviewed. Subsequently, we will focus on some recent examples related with the employment of electrochemical, photochemical, and chemical strategies to carry out the nicotinamide coenzyme or the flavin/heme prosthetic group regeneration. In the case of biocatalysts that use NAD(P) as electron shuttle, these systems have also been employed to replace it, allowing the design of nicotinamide-free recycling setups. In all cases, the (dis)advantages that these methodologies present will be briefly discussed.

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“…While in an older study only mandelic acid was transformed [58], other mandelic acid derivatives have been investigated more recently [59]. In this redox-neutral cascade that proceeds via 'hydrogen borrowing', an engineered mandelate racemase (MRM) from Pseudomonas putida, a D-mandelate dehydrogenase (D-MDH) from Lactobacillus brevis, and an L-leucine dehydrogenase (LeuDH) from Exiguobacterium sibiricum were selected to produce L-phenyl glycine derivatives 38 in a one-pot simultaneous fashion (Scheme 10).…”

Section: α-And β-Amino Acidsmentioning

confidence: 99%

Artificial Biocatalytic Linear Cascades to Access Hydroxy Acids, Lactones, and α- and β-Amino Acids

2018

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α-, β-, and ω-Hydroxy acids, amino acids, and lactones represent common building blocks and intermediates for various target molecules. This review summarizes artificial cascades published during the last 10 years leading to these products. Renewables as well as compounds originating from fossil resources have been employed as starting material. The review provides an inspiration for new cascade designs and may be the basis to design variations of these cascades starting either from alternative substrates or extending them to even more sophisticated products.

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Deracemisation of Mandelic Acid to Optically Pure Non‐Natural L‐Phenylglycine via a Redox‐Neutral Biocatalytic Cascade

Cited by 94 publications

References 35 publications

Conversion of alcohols to enantiopure amines through dual-enzyme hydrogen-borrowing cascades

Conversion of alcohols to enantiopure amines through dual-enzyme hydrogen-borrowing cascades

Recent Advances in Cofactor Regeneration Systems Applied to Biocatalyzed Oxidative Processes

Artificial Biocatalytic Linear Cascades to Access Hydroxy Acids, Lactones, and α- and β-Amino Acids

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