A5087088536- Catalytic C–H Functionalization Methods
- Enzyme Catalysis and Immobilization
- Radical Photochemical Reactions
- Cyclopropane Reaction Mechanisms
- Synthesis and Catalytic Reactions
- Sulfur-Based Synthesis Techniques
- X-ray Diffraction in Crystallography
- Chemical Synthesis and Analysis
- Crystallization and Solubility Studies
- CO2 Reduction Techniques and Catalysts
- Synthetic Organic Chemistry Methods
- Asymmetric Hydrogenation and Catalysis
- Steroid Chemistry and Biochemistry
- Innovative Microfluidic and Catalytic Techniques Innovation
- Metal-Catalyzed Oxygenation Mechanisms
- Chemical Synthesis and Reactions
- Click Chemistry and Applications
- Amino Acid Enzymes and Metabolism
- Biochemical and Molecular Research
- Chemical synthesis and alkaloids
- Catalytic Cross-Coupling Reactions
- Enzyme function and inhibition
- Synthesis and Biological Evaluation
- Carbohydrate Chemistry and Synthesis
- Protein purification and stability
Merck & Co., Inc., Rahway, NJ, USA (United States)
2018-2023
California Institute of Technology
2015-2019
Princeton University
2011-2018
Princeton Public Schools
2014
University of Pennsylvania
2011
United States Military Academy
2011
Philadelphia University
2011
An unanticipated photocatalytic carbon-carbon bond-forming reaction emerged from screening many unusual reagent combinations.
The direct α-heteroarylation of tertiary amines has been accomplished<italic>via</italic>photoredox catalysis to generate valuable benzylic amine pharmacophores.
Despite the astonishing breadth of enzymes in nature, no are known for many valuable catalytic transformations discovered by chemists. Recent work enzyme design and evolution, however, gives us good reason to think that this will change. We describe a chemomimetic biocatalysis approach draws from small-molecule catalysis synthetic chemistry, enzymology, molecular evolution discover or create with non-natural reactivities. illustrate how cofactor-dependent can be exploited promote reactions...
Abstract Chiral 1,2‐amino alcohols are widely represented in biologically active compounds from neurotransmitters to antivirals. While many synthetic methods have been developed for accessing amino alcohols, the direct aminohydroxylation of alkenes unprotected, enantioenriched remains a challenge. Using directed evolution, we engineered hemoprotein biocatalyst based on thermostable cytochrome c that directly transforms with high enantioselectivity (up 2500 TTN and 90 % ee ) under anaerobic...
The repurposing of hemoproteins for non-natural carbene transfer activities has generated enzymes functions previously accessible only to chemical catalysts. With constrained specific substrate classes, however, the synthetic utility these new biocatalysts been limited. To expand capabilities biocatalysis, we engineered variants Cytochrome P450BM3 that catalyze cyclopropanation heteroatom-bearing alkenes, providing valuable nitrogen-, oxygen-, and sulfur-substituted cyclopropanes. Four or...
Abstract Sigmatropic rearrangements, while rare in biology, offer opportunities for the efficient and selective synthesis of complex chemical motifs. A “P411” serine‐ligated variant cytochrome P450 BM3 has been engineered to initiate a sulfimidation/[2,3]‐sigmatropic rearrangement sequence whole E. coli cells, non‐natural function any enzyme, providing access enantioenriched, protected allylic amines. Five mutations enzyme substantially enhance its activity toward this new function,...
Enzymes are capable of unique and selective transformations that can enable efficient chemical production. While many industrial processes have been developed using free enzymes in aqueous solutions, immobilizing on a solid support offer considerable advantages, including improved reaction efficiency, enzyme stability, the ability to perform reactions non-aqueous media, simplified separation product from enzyme. Herein, we describe development biocatalytic transaminase Cyrene (2) utilizing...
The development of a protecting group-free, 2-step synthesis 5-amino-2-hydroxymethyltetrahydropyran 1a from biorenewable Cyrene™ is described which renders access to BTK-inhibitor nemtabrutinib (2) more efficient and sustainable.
Abstract Sigmatropic rearrangements, while rare in biology, offer opportunities for the efficient and selective synthesis of complex chemical motifs. A “P411” serine‐ligated variant cytochrome P450 BM3 has been engineered to initiate a sulfimidation/[2,3]‐sigmatropic rearrangement sequence whole E. coli cells, non‐natural function any enzyme, providing access enantioenriched, protected allylic amines. Five mutations enzyme substantially enhance its activity toward this new function,...
Abstract Chiral 1,2‐amino alcohols are widely represented in biologically active compounds from neurotransmitters to antivirals. While many synthetic methods have been developed for accessing amino alcohols, the direct aminohydroxylation of alkenes unprotected, enantioenriched remains a challenge. Using directed evolution, we engineered hemoprotein biocatalyst based on thermostable cytochrome c that directly transforms with high enantioselectivity (up 2500 TTN and 90 % ee ) under anaerobic...
Abstract We report a practical enzymatic approach for the stereoselective synthesis of hydroxylated cyclic amino acids. Using ketoreductases, ketoesters are converted with high diastereo‐ and enantioselectivity to all isomers 3‐hydroxyproline 3‐hydroxypipecolic acid via dynamic kinetic reduction reaction. This work highlights ability enzymes provide solutions challenges in synthesis. magnified image
Azabicyclic [3.1.0] and [4.1.0] Kulinkovich products underwent a facile reduction/fragmentation to afford variety of 3-piperidinones 3-azepinones, respectively, in the presence catalytic palladium on carbon formic acid an atmosphere hydrogen.
Herein we describe the translation of an immobilized transaminase process in batch to a packed bed reactor for synthesis cyrene amine, intermediate Nemtabrutinib. This change design provided significant benefits both robustness enzyme preparation and minimization amount required perform transformation. The extended residence times high conversion led us investigate dynamic flow system quickly survey reaction kinetics under various conditions provide approximate pseudosteady state runs...
Enzymes are capable of unique and selective transformations that can enable sustainable chemical production. While many industrial processes have been developed using free enzymes in aqueous solutions, immobilizing on a solid support offer considerable advantages, including improved reaction efficiency, enzyme stability, the ability to perform reactions non-aqueous media, simplified separation product from enzyme. Herein, we describe development biocatalytic transaminase CyreneTM (2)...
Abstract Review: 291 refs.
The construction of C–N bonds is essential for the preparation numerous molecules critical to modern society1,2. Nature has evolved enzymes facilitate these transformations using nucleophilic and nitrene transfer mechanisms3,4. However, neither natural nor engineered are known generate control nitrogen-centered radicals, which serve as valuable species bond formation. Herein, we describe a platform generating radicals within protein active sites, thus enabling asymmetric hydroamination...
Abstract Five‐ (II) and six‐membered heteroarenes (IV) are viable coupling partners for the title reaction with cyclic acyclic amines [(I) (VI)].