Asymmetrische Synthesen mit 2‐Trifluormethyl‐Δ<sup>3</sup>‐oxazolinonen‐(5), II. Umwandlung von racem. tert.‐Leucin in das L‐Enantiomere

Steglich, Wölfgang; Frauendorfer, Erich; Weygand, Friedrich

doi:10.1002/cber.19711040303

Cited by 24 publications

(4 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The synthesis and characterization of Boc‐ L ‐Tle‐OH, of Z‐ L ‐Tle‐OH and its dicyclohexylammonium salt, and of Z‐ L ‐Tle‐O t Bu have already been reported 47. 48 All newly synthesized compounds were also characterized by 1 H NMR spectroscopy and ESI‐TOF mass spectrometry.…”

Section: Resultsmentioning

confidence: 99%

Enantioselective Merger of Aminocatalysis with π‐Lewis Acid Metal Catalysis: Asymmetric Preparation of Carbo‐ and Heterocycles

et al. 2013

View full text Add to dashboard Cite

The metallo‐organocatalyzed enantioselective synthesis of various five‐membered carbo‐ and heterocyclic structures through the merger of aminocatalysis with the catalytic indium(III) or copper(I) activation of α‐disubstituted formyl alkynes is described. The use of indium trichloride associated with the (R)‐1,1′‐bis‐(2‐naphthylamine) ligand led to encouraging results with up to 85:15 enantiomeric ratio. After a careful examination of several other strategies, the best synergic catalytic system, which combines a chiral copper(I) complex with cyclohexylamine, afforded the enantioselective preparations of cyclopentane, indane, and pyrrolidine scaffolds with moderate to excellent control of the all‐carbon quaternary stereogenic centers created through such cyclization processes.

show abstract

Section: Resultsmentioning

confidence: 99%

Enantioselective Merger of Aminocatalysis with π‐Lewis Acid Metal Catalysis: Asymmetric Preparation of Carbo‐ and Heterocycles

et al. 2013

View full text Add to dashboard Cite

show abstract

“…The generation of oxazolone 20 has been described in the literature via approaches that are similar to those described here and also by the treatment of tert -leucine with TFAA. The formation of 20 was confirmed under each of these conditions by nuclear magnetic resonance analysis. − While inconsequential for the outcome of the reaction, the stereochemistry of the carbon bearing the trifluoromethyl group remains unclear in the mechanism proposed.…”

Section: Stereochemical Outcome Of the Amidation Reactionmentioning

confidence: 90%

Synthesis of Nirmatrelvir: Development of an Efficient, Scalable Process to Generate the Western Fragment

Algera,

Allais,

Baldwin

et al. 2023

Org. Process Res. Dev.

View full text Add to dashboard Cite

Nirmatrelvir (1), a novel and specific inhibitor of the SARS-CoV-2 3C-like protease, was developed by Pfizer scientists in mid 2020. Efforts to develop a scalable process to manufacture nirmatrelvir were undertaken with a great sense of urgency, as there were no effective treatments available for the worldwide patient population at that time. We used a convergent approach to generate this molecule. The first two steps used to generate the western fragment of nirmatrelvir from L-tert-leucine, ethyl trifluoroacetate, and a [3.1.0] bicyclic proline derivative are described here. This is the first of a series of four papers describing the commercial process of the development of nirmatrelvir.

show abstract

“…The synthesis method of L-Tle includes chemical and biological methods. Compared with traditional chemical synthesis (Pracejus, 1964;Steglich et al, 1971;Jaeger and Broadhurst, 1979;Kunz et al, 1989;Corey and Link, 1992), the enzymatic reduction of chiral keto acid to synthesize the corresponding unnatural amino acid has the advantages of high optical purity, mild reaction conditions, high conversion rate, and environmental friendliness (Kragl and Dwars, 2001; Ghislieri and Turner, 2014;Cheng et al, 2016). As the trigger of the enzyme reaction for the biosynthesis of L-Tle, Leucine dehydrogenase (LeuDH, EC 1.4.1.9) is a NAD +dependent oxidoreductase that catalyzes the formation of chiral unnatural amino acids by chiral keto acids (Xu et al, 2017), as shown in Figure 1.…”

Section: Introductionmentioning

confidence: 99%

Cloning and Expression of a Novel Leucine Dehydrogenase: Characterization and L-tert-Leucine Production

Luo

Zhu

Zhao

et al. 2020

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

Among many genes encoding for amino acid dehydrogenase, a novel leucine dehydrogenase gene from Exiguobacterium sibiricum (EsiLeuDH) was isolated by using genome mining strategy. EsiLeuDH was overexpressed in Escherichia coli BL21 (DE3), followed by purification and characterization. The high thermostability of the enzyme confers its half-life up to 14.7 h at 50 • C. Furthermore, the substrate specificity shows a broad spectrum, including many L-amino acids and aliphatic α-keto acids, especially some aryl α-keto acids. This enzyme coupled with recombinant formate dehydrogenase (FDH) was used to catalyze trimethylpyruvic acid (TMP) through reductive amination to generate enantiopure L-tert-leucine (L-Tle). In order to overcome the substrate inhibition effect, a fed-batch feeding strategy was adopted to transform up to 0.8 M of TMP to L-Tle, with an average conversion rate of 81% and L-Tle concentration of 65.6 g•L −1. This study provides a highly efficient biocatalyst for the synthesis of L-Tle and lays the foundation for large-scale production and application of chiral non-natural amino acids.

show abstract

Asymmetrische Synthesen mit 2‐Trifluormethyl‐Δ³‐oxazolinonen‐(5), II. Umwandlung von racem. tert.‐Leucin in das L‐Enantiomere

Cited by 24 publications

References 13 publications

Enantioselective Merger of Aminocatalysis with π‐Lewis Acid Metal Catalysis: Asymmetric Preparation of Carbo‐ and Heterocycles

Enantioselective Merger of Aminocatalysis with π‐Lewis Acid Metal Catalysis: Asymmetric Preparation of Carbo‐ and Heterocycles

Synthesis of Nirmatrelvir: Development of an Efficient, Scalable Process to Generate the Western Fragment

Cloning and Expression of a Novel Leucine Dehydrogenase: Characterization and L-tert-Leucine Production

Contact Info

Product

Resources

About

Asymmetrische Synthesen mit 2‐Trifluormethyl‐Δ3‐oxazolinonen‐(5), II. Umwandlung von racem. tert.‐Leucin in das L‐Enantiomere

Cited by 24 publications

References 13 publications

Enantioselective Merger of Aminocatalysis with π‐Lewis Acid Metal Catalysis: Asymmetric Preparation of Carbo‐ and Heterocycles

Enantioselective Merger of Aminocatalysis with π‐Lewis Acid Metal Catalysis: Asymmetric Preparation of Carbo‐ and Heterocycles

Synthesis of Nirmatrelvir: Development of an Efficient, Scalable Process to Generate the Western Fragment

Cloning and Expression of a Novel Leucine Dehydrogenase: Characterization and L-tert-Leucine Production

Contact Info

Product

Resources

About

Asymmetrische Synthesen mit 2‐Trifluormethyl‐Δ³‐oxazolinonen‐(5), II. Umwandlung von racem. tert.‐Leucin in das L‐Enantiomere