Mechanism‐Inspired Engineering of Phenylalanine Aminomutase for Enhanced β‐Regioselective Asymmetric Amination of Cinnamates

Wu, Bian; Szymański, Wiktor; Wybenga, Gjalt G.; Heberling, Matthew M.; Bartsch, Sebastian; Wildeman, S. De; Poelarends, Gerrit J.; Feringa, Ben L.; Dijkstra, Bauke W.; Janssen, Dick B.

doi:10.1002/ange.201106372

Cited by 22 publications

(41 citation statements)

References 46 publications

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“…The most general route to β‐amino acids is by the action of a family of amino acid mutases on the corresponding α‐amino acids. Two types of microbial enzymes have been observed to have such mutase activity 116. 117 One involves conversion of Phe or Tyr into the corresponding β‐amino acids.…”

Section: Generation Of Nonproteinogenic Amino Acid Building Blocksmentioning

confidence: 99%

Metal‐Free Reduction of CO₂ with Hydroboranes: Two Efficient Pathways at Play for the Reduction of CO₂ to Methanol

Gomes

Blondiaux

Thuéry

et al. 2014

Chemistry A European J

156

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Guanidines and amidines prove to be highly efficient metal-free catalysts for the reduction of CO2 to methanol with hydroboranes such as 9-borabicyclo[3.3.1]nonane (9-BBN) and catecholborane (catBH). Nitrogen bases, such as 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (Me-TBD), and 1,8-diazabicycloundec-7-ene (DBU), are active catalysts for this transformation and Me-TBD can catalyze the reduction of CO2 to methoxyborane at room temperature with TONs and TOFs of up to 648 and 33 h(-1) (25 °C), respectively. Formate HCOOBR2 and acetal H2C(OBR2)2 derivatives have been identified as reaction intermediates in the reduction of CO2 with R2BH, and the first C-H-bond formation is rate determining. Experimental and computational investigations show that TBD and Me-TBD follow distinct mechanisms. The N-H bond of TBD is reactive toward dehydrocoupling with 9-BBN and affords a novel frustrated Lewis pair (FLP) that can activate a CO2 molecule and form the stable adduct 2, which is the catalytically active species and can facilitate the hydride transfer from the boron to the carbon atoms. In contrast, Me-TBD promotes the reduction of CO2 through the activation of the hydroborane reagent. Detailed DFT calculations have shown that the computed energy barriers for the two mechanisms are consistent with the experimental findings and account for the reactivity of the different boron reductants.

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Section: Generation Of Nonproteinogenic Amino Acid Building Blocksmentioning

confidence: 99%

Metal‐Free Reduction of CO₂ with Hydroboranes: Two Efficient Pathways at Play for the Reduction of CO₂ to Methanol

Gomes

Blondiaux

Thuéry

et al. 2014

Chemistry A European J

156

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“…This led to the synthesis of almost pure (R)-b-phenylalanine and derivatives through the asymmetric amination of cinnamic acid. [107] To generate enantiopure b-phenylalanines, Wu et al established an efficient tandem biocatalytic process from aromatic b-amino acid racemates (Scheme 22). In their approach, enantiopure (S)-b-phenylalanines (S)-78 a,b were prepared by coupling the PAM-catalyzed stereoselective isomerization with the PAL-catalyzed deamination of l-79 a,b.…”

Section: Aminomutasesmentioning

confidence: 99%

New Generation of Biocatalysts for Organic Synthesis

et al. 2014

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The use of enzymes as catalysts for the preparation of novel compounds has received steadily increasing attention over the past few years. High demands are placed on the identification of new biocatalysts for organic synthesis. The catalysis of more ambitious reactions reflects the high expectations of this field of research. Enzymes play an increasingly important role as biocatalysts in the synthesis of key intermediates for the pharmaceutical and chemical industry, and new enzymatic technologies and processes have been established. Enzymes are an important part of the spectrum of catalysts available for synthetic chemistry. The advantages and applications of the most recent and attractive biocatalysts--reductases, transaminases, ammonia lyases, epoxide hydrolases, and dehalogenases--will be discussed herein and exemplified by the syntheses of interesting compounds.

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“…die Phenylalanin‐Aminomutase aus Taxus chinensis durch Struktur‐ und Mechanismus‐basiertes Protein‐Engineering in eine selektive β‐Lyase umgewandelt. Damit wurde die Synthese von beinahe reinem ( R )‐β‐Phenylalanin und seinen Derivaten durch die asymmetrische Aminierung von Zimtsäure erreicht 107…”

Section: Enzyme Zur Herstellung Chiraler Amine Und Aminosäurenunclassified

Biokatalysatoren für die organische Synthese – die neue Generation

et al. 2014

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Die Verwendung von Enzymen als Katalysatoren zur Synthese neuartiger Verbindungen ist in den letzten Jahren zunehmend in den Fokus gerückt. Entsprechend hohe Erwartungen werden an die Entdeckung und Identifizierung neuer Biokatalysatoren für die organische Synthese gestellt. Dies spiegelt sich auch in der Komplexität der adressierten Reaktionen wider. Der Anwendungsbereich von Biokatalysatoren umfasst die Synthese wichtiger Zwischenprodukte für die pharmazeutische und chemische Industrie sowie die Entwicklung neuer enzymatischer Techniken und Prozesse. Enzyme sind ein wichtiger Teil des Spektrums an Katalysatoren, die der Synthesechemie zur Verfügung stehen. Die Vorteile und Anwendungsmöglichkeiten der neuesten und höchst vielversprechenden Generation von Biokatalysatoren – Reduktasen, Transaminasen, Ammoniak‐Lyasen, Epoxidhydrolasen und Dehalogenasen – werden hier vorgestellt und anhand der Synthese von Schlüsselmolekülen beispielhaft diskutiert.

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Mechanism‐Inspired Engineering of Phenylalanine Aminomutase for Enhanced β‐Regioselective Asymmetric Amination of Cinnamates

Cited by 22 publications

References 46 publications

Metal‐Free Reduction of CO₂ with Hydroboranes: Two Efficient Pathways at Play for the Reduction of CO₂ to Methanol

Metal‐Free Reduction of CO₂ with Hydroboranes: Two Efficient Pathways at Play for the Reduction of CO₂ to Methanol

New Generation of Biocatalysts for Organic Synthesis

Biokatalysatoren für die organische Synthese – die neue Generation

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Mechanism‐Inspired Engineering of Phenylalanine Aminomutase for Enhanced β‐Regioselective Asymmetric Amination of Cinnamates

Cited by 22 publications

References 46 publications

Metal‐Free Reduction of CO2 with Hydroboranes: Two Efficient Pathways at Play for the Reduction of CO2 to Methanol

Metal‐Free Reduction of CO2 with Hydroboranes: Two Efficient Pathways at Play for the Reduction of CO2 to Methanol

New Generation of Biocatalysts for Organic Synthesis

Biokatalysatoren für die organische Synthese – die neue Generation

Contact Info

Product

Resources

About

Metal‐Free Reduction of CO₂ with Hydroboranes: Two Efficient Pathways at Play for the Reduction of CO₂ to Methanol

Metal‐Free Reduction of CO₂ with Hydroboranes: Two Efficient Pathways at Play for the Reduction of CO₂ to Methanol