Browse
Submit Data
Databases
API
Help

Dataset Information

21 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Enzyme-controlled nitrogen-atom transfer enables regiodivergent C-H amination.

ABSTRACT: We recently demonstrated that variants of cytochrome P450BM3 (CYP102A1) catalyze the insertion of nitrogen species into benzylic C-H bonds to form new C-N bonds. An outstanding challenge in the field of C-H amination is catalyst-controlled regioselectivity. Here, we report two engineered variants of P450BM3 that provide divergent regioselectivity for C-H amination-one favoring amination of benzylic C-H bonds and the other favoring homo-benzylic C-H bonds. The two variants provide nearly identical kinetic isotope effect values (2.8-3.0), suggesting that C-H abstraction is rate-limiting. The 2.66-Å crystal structure of the most active enzyme suggests that the engineered active site can preorganize the substrate for reactivity. We hypothesize that the enzyme controls regioselectivity through localization of a single C-H bond close to the iron nitrenoid.

SUBMITTER: Hyster TK

PROVIDER: S-EPMC4227740 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Enzyme-controlled nitrogen-atom transfer enables regiodivergent C-H amination.

Hyster Todd K TK Farwell Christopher C CC Buller Andrew R AR McIntosh John A JA Arnold Frances H FH

Journal of the American Chemical Society 20141024 44

We recently demonstrated that variants of cytochrome P450BM3 (CYP102A1) catalyze the insertion of nitrogen species into benzylic C-H bonds to form new C-N bonds. An outstanding challenge in the field of C-H amination is catalyst-controlled regioselectivity. Here, we report two engineered variants of P450BM3 that provide divergent regioselectivity for C-H amination-one favoring amination of benzylic C-H bonds and the other favoring homo-benzylic C-H bonds. The two variants provide nearly identica ...[more]

PMID: 25325618

Similar Datasets

Enantioselective imidation of sulfides via enzyme-catalyzed intermolecular nitrogen-atom transfer.

Project description:Engineering enzymes with novel reaction modes promises to expand the applications of biocatalysis in chemical synthesis and will enhance our understanding of how enzymes acquire new functions. The insertion of nitrogen-containing functional groups into unactivated C-H bonds is not catalyzed by known enzymes but was recently demonstrated using engineered variants of cytochrome P450BM3 (CYP102A1) from Bacillus megaterium. Here, we extend this novel P450-catalyzed reaction to include intermolecular insertion of nitrogen into thioethers to form sulfimides. An examination of the reactivity of different P450BM3 variants toward a range of substrates demonstrates that electronic properties of the substrates are important in this novel enzyme-catalyzed reaction. Moreover, amino acid substitutions have a large effect on the rate and stereoselectivity of sulfimidation, demonstrating that the protein plays a key role in determining reactivity and selectivity. These results provide a stepping stone for engineering more complex nitrogen-atom-transfer reactions in P450 enzymes and developing a more comprehensive biocatalytic repertoire.

| S-EPMC4154708 | biostudies-literature

Merging Regiodivergent Catalysis with Atom-Economical Radical Arylation.

Project description:A titanocene-catalyzed regiodivergent radical arylation is described that allows access to either enantiomerically pure tetrahydroquinolines or indolines from a common starting material. The regioselectivity of epoxide opening that results in the high selectivity of heterocycle formation is controlled by two factors, the absolute configuration of the enantiopure ligands of the (C5 H4 R)2 TiX2 catalyst and the inorganic ligand X (X=Cl, OTs). The overall reaction is atom-economical and constitutes a radical Friedel-Crafts alkylation.

| S-EPMC6852184 | biostudies-literature

Nitrogen-Mediated Graphene Oxide Enables Highly Efficient Proton Transfer.

Project description:Two-dimensional (2D) graphene and graphene oxide (GO) offer great potential as a new type of cost-efficient proton-exchange membranes (PEM) for electrochemical devices. However, fundamental issues of proton transfer mechanism via 2D membranes are unclear and the transfer barrier for perfect graphene are too high for practical application. Using ab initio molecular dynamic simulations, we screened the proton transfer barrier for different un-doped and nitrogen doped GO membranes, and clarified the corresponding transfer mechanisms. More significantly, we further identify that N-mediated GO can be built into a highly efficient PEM with a proton transfer rate of seven orders of magnitude higher than an un-doped case via. a proton relay mechanism between a ketone-like oxygen and a pyridine-like nitrogen across the vacancy site. The N-doped 2D GO is also impermeable to small molecules, and hence a highly efficient PEM for practical applications.

| S-EPMC5507853 | biostudies-other

Phenothiazinimides: Atom-Efficient Electrophilic Amination Reagents.

Project description:Phenothiazinimides, a fairly unknown class of imines, were prepared and found to be very reactive as ultrasimple atom-efficient electrophilic amination reagents for phenols and indoles under metal-free conditions.

| S-EPMC6045521 | biostudies-literature

Nitrogen Atom Transfer Catalysis by Metallonitrene C-H Insertion: Photocatalytic Amidation of Aldehydes.

Project description:C-H amination and amidation by catalytic nitrene transfer are well-established and typically proceed via electrophilic attack of nitrenoid intermediates. In contrast, the insertion of (formal) terminal nitride ligands into C-H bonds is much less developed and catalytic nitrogen atom transfer remains unknown. We here report the synthesis of a formal terminal nitride complex of palladium. Photocrystallographic, magnetic, and computational characterization support the assignment as an authentic metallonitrene (Pd-N) with a diradical nitrogen ligand that is singly bonded to PdII . Despite the subvalent nitrene character, selective C-H insertion with aldehydes follows nucleophilic selectivity. Transamidation of the benzamide product is enabled by reaction with N3 SiMe3 . Based on these results, a photocatalytic protocol for aldehyde C-H trimethylsilylamidation was developed that exhibits inverted, nucleophilic selectivity as compared to typical nitrene transfer catalysis. This first example of catalytic C-H nitrogen atom transfer offers facile access to primary amides after deprotection.

| S-EPMC9305406 | biostudies-literature

Reagent-controlled regiodivergent ring expansions of steroids.

Project description:Ring expansion provides a powerful way of introducing a heteroatom substituent into a carbocyclic framework. However, such reactions are often limited by the tendency of a given substrate to afford only one of the two rearrangement products or fail to achieve high selectivity at all. These limitations are particularly acute when seeking to carry out late-stage functionalization of natural products as starting points in drug discovery. In this work, we present a stereoelectronically controlled ring expansion sequence towards selective and flexible access to complementary ring systems derived from common steroidal substrates. Chemical diversification of the reaction intermediate affords over 100 isomerically pure analogs with spatial and functional diversity. This regiodivergent rearrangement, and the concept of using chiral reagents to affect regiocontrol in chiral natural products, should be broadly applicable to late-stage natural product diversification programs.

| S-EPMC5838248 | biostudies-other

Vinylogous Nitro-Haloform Reaction Enables Aromatic Amination.

Project description:The first example of an aromatic haloform reaction is reported, defining a conceptually new haloform-type approach to the metal-free functionalization of arenes. We demonstrated that heteroarenes bearing a vinylogous nitromethane system, via the stage of a trichloromethane derivative, could undergo aromatic amination to produce N-functionalized arenes in quantitative yields and without the need for transition-metal catalysis. The haloform-type amination was implemented in the development of effective orthogonal N-protection strategies, establishing a new promising N-protecting reagent.

| S-EPMC9274776 | biostudies-literature

Catalyst Controlled Regiodivergent Arylboration of Dienes.

Project description:A method for the regiodivergent arylboration of dienes is presented. These reactions allow for the formation of a diverse range of synthetically versatile products from simple precursors. Through mechanistic studies, these reactions likely operate by initial addition of a Cu-Bpin complex across the diene followed by Pd-catalyzed cross coupling with an aryl halide or pseudohalide.

| S-EPMC5618444 | biostudies-literature

Mechanism of Iminium Salt-Catalyzed C(sp<sup>3</sup>)-H Amination: Factors Controlling Hydride Transfer versus H-Atom Abstraction.

Project description:Carbon-nitrogen bonds are extremely prevalent in pharmaceuticals, natural products, and other biologically relevant molecules such as nucleic acids and proteins. Intermolecular amination of C(sp3)-H bonds by catalytic nitrene transfer is a promising method for forging C-N bonds. An organocatalytic approach to nitrene transfer by way of an iminium salt offers a site-selective method for C(sp3)-H amination. Understanding of this amination mechanism including the nature of the relevant intermediates and the factors controlling the mechanism of the N-H bond formation step would aid in the design of catalysts and C(sp3)-H amination methods. In this work, the mechanism of the iminium salt-catalyzed C(sp3)-H amination via nitrene transfer was elucidated computationally using quantum mechanical methods and molecular dynamics simulations. Dispersion-corrected density functional theory (DFT) calculations provide support for an open singlet biradical species in equilibrium with the lower energy triplet species. Calculations further reveal that while the singlet biradical species undergoes N-H bond formation by a hydride transfer process, the triplet species forms the N-H bond by H-atom abstraction. Molecular dynamics (MD) simulations rule out the possibility of a fast rebound of the carbon substrate following N-H bond formation. A predictive model for mode of activation and site-selectivity that is consistent with experimental observations is presented.

| S-EPMC8188841 | biostudies-literature

Chiral Hypervalent Iodine Catalysis Enables an Unusual Regiodivergent Intermolecular Olefin Aminooxygenation.

Project description:A novel iodide-catalyzed intermolecular aminooxygenation strategy is described here. Amide is used as the O- and N- source to probe for regiocontrol strategies. Notably, simple additives can be selectively introduced to achieve regiodivergent oxyamination processes for electronically activated alkenes while being regio-complementary for unactivated alkenes. Our preliminary data demonstrates that this regiocontrol strategy based on nucleophile can also be applied in asymmetric processes using chiral hypervalent iodine catalysis.

| S-EPMC8243328 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data