One Pot Asymmetric Synthesis of (<i>R</i>)‐Phenylglycinol from Racemic Styrene Oxide via Cascade Biocatalysis

Sun, Zai‐Bao; Zhang, Zhi Jun; Li, Fulong; Nie, Yao; Yu, Hui‐Lei; Xu, Jian‐He

doi:10.1002/cctc.201900492

Cited by 26 publications

(12 citation statements)

References 55 publications

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“…27 Remarkably, the GlyDH from Enterobacter (Klebsiella) aerogenes oxidises the R-phenylglycol to 2-hydroxyacetophenone in a regio-and enantioselective manner. 28 Hundreds of examples endorse the improvement of enzyme properties (activity, stability and selectivity) and the widening of their substrate scope through protein engineering. As safe path for enzyme optimization, the scientic community exploits, either separately or synergistically, random and extensive mutagenesis campaigns through directed evolution 29 and minimalist mutations through site-directed mutagenesis guided by structural knowledge.…”

Section: Introductionmentioning

confidence: 99%

Selective oxidation of alkyl and aryl glyceryl monoethers catalysed by an engineered and immobilised glycerol dehydrogenase

et al. 2020

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Section: Introductionmentioning

confidence: 99%

Selective oxidation of alkyl and aryl glyceryl monoethers catalysed by an engineered and immobilised glycerol dehydrogenase

et al. 2020

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“…A promising application would be the direct chiral detection of the raw constituents of one pot asymmetric synthesis reactions, similar to ones by [37,38]. Inside this flask, there are: reactants, solvents, products, by-products, and catalysts.…”

Section: Discussionmentioning

confidence: 99%

Assignment-free chirality detection in unknown samples via microwave three-wave mixing

Koumarianou

Wang

Satterhwaite

et al. 2021

Preprint

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Straightforward identification of chiral molecules in multi-component mixtures of unknown composition is extremely challenging. Current spectrometric and chromatographic methods cannot unambiguously identify components while the state of the art spectroscopic methods are limited by the difficult and time-consuming task of spectral assignment. Here, we introduce a highly sensitive generalized version of microwave three-wave mixing that uses broad-spectrum fields to detect chiral molecules in enantiomeric excess without any prior chemical knowledge of the sample. This method does not require spectral assignment as a necessary step to extract information out of a spectrum. We demonstrate our method by recording three-wave mixing spectra of multi-component samples that provide direct evidence of enantiomeric excess. Our method opens up new capabilities in ultrasensitive phase-coherent spectroscopic detection that can be applied for chiral detection in real-life mixtures, raw products of chemical reactions and difficult to assign novel exotic species.

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“…A chemo-biocatalytic route toward phenylethanolamines entails the ring-opening of styrene oxide with ammonia under microwave irradiation; styrene oxide is obtained from the bioepoxidation of styrene with a styrene monooxygenase . In full biocatalytic approaches, linear cascades have been demonstrated to be viable options due to their often high selectivity and atom efficiency. , Notable examples are a multienzymatic cascade for the asymmetric synthesis of ( R )-2-phenylglycinol (( R )- 7 ) from racemic styrene oxide ( 4 ); a one-pot three-step enzymatic process to convert a series of halo ketones to the corresponding amino alcohols, including the natural antiviral product ( S )-tembamide; the conversion of styrene to ( S )-phenylethanolamine (( S )- 9 ) by modular cascade biocatalysis; and the engineered hemoprotein-catalyzed direct enantioselective aminohydroxylation of olefins …”

Section: Introductionmentioning

confidence: 99%

High-Yield Synthesis of Enantiopure 1,2-Amino Alcohols from l-Phenylalanine via Linear and Divergent Enzymatic Cascades

Corrado

Knaus

Schwaneberg

et al. 2022

Org. Process Res. Dev.

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Enantiomerically pure 1,2-amino alcohols are important compounds due to their biological activities and wide applications in chemical synthesis. In this work, we present two multienzyme pathways for the conversion of l -phenylalanine into either 2-phenylglycinol or phenylethanolamine in the enantiomerically pure form. Both pathways start with the two-pot sequential four-step conversion of l -phenylalanine into styrene via subsequent deamination, decarboxylation, enantioselective epoxidation, and enantioselective hydrolysis. For instance, after optimization, the multienzyme process could convert 507 mg of l -phenylalanine into ( R )-1-phenyl-1,2-diol in an overall isolated yield of 75% and >99% ee. The opposite enantiomer, ( S )-1-phenyl-1,2-diol, was also obtained in a 70% yield and 98–99% ee following the same approach. At this stage, two divergent routes were developed to convert the chiral diols into either 2-phenylglycinol or phenylethanolamine. The former route consisted of a one-pot concurrent interconnected two-step cascade in which the diol intermediate was oxidized to 2-hydroxy-acetophenone by an alcohol dehydrogenase and then aminated by a transaminase to give enantiomerically pure 2-phenylglycinol. Notably, the addition of an alanine dehydrogenase enabled the connection of the two steps and made the overall process redox-self-sufficient. Thus, ( S )-phenylglycinol was isolated in an 81% yield and >99.4% ee starting from ca. 100 mg of the diol intermediate. The second route consisted of a one-pot concurrent two-step cascade in which the oxidative and reductive steps were not interconnected. In this case, the diol intermediate was oxidized to either ( S )- or ( R )-2-hydroxy-2-phenylacetaldehyde by an alcohol oxidase and then aminated by an amine dehydrogenase to give the enantiomerically pure phenylethanolamine. The addition of a formate dehydrogenase and sodium formate was required to provide the reducing equivalents for the reductive amination step. Thus, ( R )-phenylethanolamine was isolated in a 92% yield and >99.9% ee starting from ca. 100 mg of the diol intermediate. In summary, l -phenylalanine was converted into enantiomerically pure 2-phenylglycinol and phenylethanolamine in overall yields of 61% and 69%, respectively. This work exemplifies how linear and divergent enzyme cascades can enable the synthesis of high-value chiral molecules such as amino alcohols from a renewable material such as l -phenylalanine with high atom economy and improved sustainability.

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One Pot Asymmetric Synthesis of (R)‐Phenylglycinol from Racemic Styrene Oxide via Cascade Biocatalysis

Cited by 26 publications

References 55 publications

Selective oxidation of alkyl and aryl glyceryl monoethers catalysed by an engineered and immobilised glycerol dehydrogenase

Selective oxidation of alkyl and aryl glyceryl monoethers catalysed by an engineered and immobilised glycerol dehydrogenase

Assignment-free chirality detection in unknown samples via microwave three-wave mixing

High-Yield Synthesis of Enantiopure 1,2-Amino Alcohols from l-Phenylalanine via Linear and Divergent Enzymatic Cascades

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