scholarly journals Engineering of Reductive Aminases for Asymmetric Synthesis of Enantiopure Rasagiline

2021 ◽  
Vol 9 ◽  
Author(s):  
Kai Zhang ◽  
Yuanzhi He ◽  
Jiawei Zhu ◽  
Qi Zhang ◽  
Luyao Tang ◽  
...  
Keyword(s):  
Transition Metal ◽  
Chemical Synthesis ◽  
Asymmetric Synthesis ◽  
Rational Design ◽  
Enantiomeric Excess ◽  
Industrial Applications ◽  
Viable Alternative ◽  
Environmentally Benign ◽  
Secondary Amines ◽  
Metal Catalyzed

Reductive aminases (RedAms) for the stereoselective amination of ketones represent an environmentally benign and economically viable alternative to transition metal–catalyzed asymmetric chemical synthesis. Here, we report two RedAms from Aspergillus calidoustus (AcRedAm) and bacteria (BaRedAm) with NADPH-dependent features. The enzymes can synthesize a set of secondary amines using a broad range of ketone and amine substrates with up to 97% conversion. To synthesize the pharmaceutical ingredient (R)-rasagiline, we engineered AcRedAm through rational design to obtain highly stereoselective mutants. The best mutant Q237A from AcRedAm could synthesize (R)-rasagiline with >99% enantiomeric excess with moderate conversion. The features of AcRedAm and BaRedAm highlight their potential for further study and expand the biocatalytic toolbox for industrial applications.

scholarly journals Protein-engineering of an amine transaminase for the stereoselective synthesis of a pharmaceutically relevant bicyclic amine

2016 ◽  
Vol 14 (43) ◽  
pp. 10249-10254 ◽  
Author(s):  
Martin S. Weiß ◽  
Ioannis V. Pavlidis ◽  
Paul Spurr ◽  
Steven P. Hanlon ◽  
Beat Wirz ◽  
...  
Keyword(s):  
Transition Metal ◽  
Protein Engineering ◽  
Asymmetric Synthesis ◽  
Stereoselective Synthesis ◽  
Environmentally Benign ◽  
Attractive Alternative ◽  
P Application ◽  
Transition Metal Catalyzed ◽  
Prochiral Ketones ◽  
Metal Catalyzed

Application of amine transaminases (ATAs) for stereoselective amination of prochiral ketones represents an environmentally benign and economically attractive alternative to transition metal catalyzed asymmetric synthesis.

scholarly journals Kinetic resolution of indolines by asymmetric hydroxylamine formation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Gang Wang ◽  
Ran Lu ◽  
Chuangchuang He ◽  
Lei Liu
Keyword(s):  
Hydrogen Peroxide ◽  
Chemical Synthesis ◽  
Late Stage ◽  
Kinetic Resolution ◽  
High Efficiency ◽  
Bond Formation ◽  
Bioactive Molecules ◽  
Environmentally Benign ◽  
Secondary Amines

AbstractCatalytic kinetic resolution of amines represents a longstanding challenge in chemical synthesis. Here, we described a kinetic resolution of secondary amines through oxygenation to produce enantiopure hydroxylamines involving N–O bond formation. The economic and practical titanium-catalyzed asymmetric oxygenation with environmentally benign hydrogen peroxide as oxidant is applicable to a range of racemic indolines with multiple stereocenters and diverse substituent patterns in high efficiency with efficient chemoselectivity and enantio-discrimination. Late-stage asymmetric oxygenation of bioactive molecules that are otherwise difficult to synthesize was also explored.

Asymmetric synthesis to chiral organosilicon compounds via transition metal-catalyzed stereoselective C-H activation and silylation

2021 ◽  
Author(s):  
Ming Zhang ◽  
Shan Gao ◽  
Juan Tang ◽  
Ling Chen ◽  
Aihua Liu ◽  
...  
Keyword(s):  
Transition Metal ◽  
Asymmetric Synthesis ◽  
Organosilicon Compounds ◽  
Feature Article ◽  
Transition Metal Catalyzed ◽  
Metal Catalyzed

This feature article introduces the progress of transition metal-catalyzed stereoselective sp2 and sp3 C-H activation and silylation to synthesize chiral organosilicon compounds, the asymmetric C-H silylation includes intramolecular cyclizing silylation...

scholarly journals Asymmetric synthesis: From transition metals to organocatalysis

2008 ◽  
Vol 80 (5) ◽  
pp. 953-966 ◽  
Author(s):  
Pavel Kočovský ◽  
Andrei V. Malkov
Keyword(s):  
Transition Metal ◽  
Transition Metals ◽  
Asymmetric Synthesis ◽  
Absolute Configuration ◽  
Nucleoside Analogs ◽  
Oxide Catalysts ◽  
Lewis Base ◽  
New Approach ◽  
Π Interactions ◽  
Metal Catalyzed

Umpolung in the allylation reaction is discussed with examples drawn from transition-metal-catalyzed allylic substitution (with the allylic unit acting as an electrophile) and Lewis base-catalyzed allylation of aldehydes with allyltrichlorosilane (with the allyl acting as a nucleophile). Iridium-catalyzed electrophilic allylation of O-nucleophiles has been employed in our new approach to C-nucleoside analogs, where the C-O bond (rather than C-C) was constructed stereospecifically. Variation of the absolute configuration in the starting segments allowed the synthesis of all four combinations of D/L-α/β-ribosides. In the nucleophilic allylation of aldehydes, chiral pyridine-type N-oxide catalysts are presented, in particular QUINOX and METHOX, and the intriguing behavior of QUINOX is discussed. Here, the π-π interactions between the substrate aldehyde and the catalyst are suggested to rationalize the experimental observations. Good correlation between the calculated energies for the transition states and the experimentally observed enantioselectivities has been obtained.

Copper-catalyzed N-(hetero)arylation of amino acids in water

RSC Advances ◽  
2016 ◽  
Vol 6 (99) ◽  
pp. 96762-96767 ◽  
Author(s):  
Krishna K. Sharma ◽  
Meenakshi Mandloi ◽  
Neha Rai ◽  
Rahul Jain
Keyword(s):  
Amino Acids ◽  
Transition Metal ◽  
Cost Effective ◽  
Environmentally Benign ◽  
Cost Effective Method ◽  
Transition Metal Catalyzed ◽  
Metal Catalyzed

A transition metal-catalyzed, environmentally benign, rapid and cost-effective method for the N-(hetero)arylation of zwitterionic amino acids in water is reported.

Asymmetric Synthesis of the Tricyclic Core of NGF-Inducing Cyathane Diterpenes via a Transition-Metal-Catalyzed [5 + 2] Cycloaddition

2001 ◽  
Vol 3 (13) ◽  
pp. 2105-2108 ◽  
Author(s):  
Paul A. Wender ◽  
F. Christopher Bi ◽  
Michael A. Brodney ◽  
Francis Gosselin
Keyword(s):  
Transition Metal ◽  
Asymmetric Synthesis ◽  
Tricyclic Core ◽  
Transition Metal Catalyzed ◽  
Metal Catalyzed
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