Browse
Submit Data
Databases
API
Help

Dataset Information

27 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

An enzymatic Alder-ene reaction.

ABSTRACT: An ongoing challenge in chemical research is to design catalysts that select the outcomes of the reactions of complex molecules. Chemists rely on organocatalysts or transition metal catalysts to control stereoselectivity, regioselectivity and periselectivity (selectivity among possible pericyclic reactions). Nature achieves these types of selectivity with a variety of enzymes such as the recently discovered pericyclases-a family of enzymes that catalyse pericyclic reactions¹. Most characterized enzymatic pericyclic reactions have been cycloadditions, and it has been difficult to rationalize how the observed selectivities are achieved^2-13. Here we report the discovery of two homologous groups of pericyclases that catalyse distinct reactions: one group catalyses an Alder-ene reaction that was, to our knowledge, previously unknown in biology; the second catalyses a stereoselective hetero-Diels-Alder reaction. Guided by computational studies, we have rationalized the observed differences in reactivities and designed mutant enzymes that reverse periselectivities from Alder-ene to hetero-Diels-Alder and vice versa. A combination of in vitro biochemical characterizations, computational studies, enzyme co-crystal structures, and mutational studies illustrate how high regioselectivity and periselectivity are achieved in nearly identical active sites.

SUBMITTER: Ohashi M

PROVIDER: S-EPMC7534572 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Diastereoselectivity on Intramolecular Alder-ene Reaction of 1,6-Dienes.

Project description:A detailed computational study of the intramolecular Alder-ene reaction of different 1,6-dienes at M06-2X(PCM)/TZ2P level of theory has been performed. We want to understand the influence of enophile-geminal substitution pattern in the cis : trans selectivity of the cyclization process. Our analysis of the reaction coordinate by means of activation strain model of chemical reactivity (ASM-distortion interaction model) reveals that the cis-selectivity observed for unactivated reagents is related with high stabilizing orbital interaction and lower strain energy, consequence of an early transition structure. On the other hand, the presence of activating groups increases the asynchronicity of the transition structures and reduces the activation barrier due to more stabilizing orbital and electrostatic interactions, favoring trans-selectivity.

| S-EPMC10087545 | biostudies-literature

Efficient Heterogeneous Copper-Catalyzed Alder-Ene Reaction of Allenynamides to Pyrrolines.

Project description:Herein, we describe an efficient nanocopper-catalyzed Alder-ene reaction of allenynamides. The copper nanoparticles were immobilized on amino-functionalized microcrystalline cellulose. A solvent-controlled chemoselectivity of the reaction was observed, leading to the chemodivergent synthesis of pyrrolines (2,5-dihydropyrroles) and pyrroles. The heterogeneous copper catalyst exhibits high efficiency and good recyclability in the Alder-ene reaction, constituting a highly attractive catalytic system from an economical and environmental point of view.

| S-EPMC8822631 | biostudies-literature

Rhodium-catalyzed intermolecular enantioselective Alder-ene type reaction of cyclopentenes with silylacetylenes.

Project description:The Alder-ene type reaction between alkenes and alkynes provides an efficient and atom-economic method for the construction of C-C bond, which has been widely employed in the synthesis of natural products and other functional molecules. The intramolecular enantioselective Alder-ene cycloisomerization reactions of 1,n-enynes have been extensively investigated. However, the intermolecular asymmetric version has not been reported, and remains a challenging task. Herein, we describe a rhodium-catalyzed intermolecular enantioselective Alder-ene type reaction of cyclopentenes with silylacetylenes. A variety of chiral (E)-vinylsilane tethered cyclopentenes bearing one quaternary carbon and one tertiary carbon stereocenters are achieved in high yields and enantioselectivities. The reaction undergoes carbonyl-directed migratory insertion, β-H elimination and desymmetrization of prochiral cyclopentenes processes.

| S-EPMC8595345 | biostudies-literature

Enzymatic Intermolecular Hetero-Diels-Alder Reaction in the Biosynthesis of Tropolonic Sesquiterpenes.

Project description:Diels-Alder reactions are among the most powerful synthetic transformations to construct complex natural products. Despite that increasing of enzymatic intramolecular Diels-Alder reactions have been discovered, natural intermolecular Diels-Alderases are rarely described. Here, we report an intermolecular hetero-Diels-Alder reaction in the biosynthesis of tropolonic sesquiterpenes and functionally characterize EupfF as the first fungal intermolecular hetero-Diels-Alderase. We demonstrate that EupfF catalyzed the dehydration of a hydroxymethyl-containing tropolone (5) to generate a reactive tropolone o-quinone methide (6) and might further stereoselectively control the subsequent intermolecular hetero-Diels-Alder reaction with (1E,4E,8Z)-humulenol (8) to produce enantiomerically pure neosetophomone B (1). Our results reveal the biosynthetic pathway of 1 and expand the repertoire of activities of Diels-Alder cyclases.

| S-EPMC6944466 | biostudies-literature

DFT Modeling of the Alternating Radical Copolymerization and Alder-Ene Reaction between Maleic Anhydride and Olefins.

Project description:The free radical copolymerization of electron-acceptor and electron-donor vinyl monomers represents a particular case of sequence-controlled polymerization. The reactions of maleic anhydride (MA) or related compounds (acceptor comonomers) with α-olefins (donor comonomers) result in the formation of the alternating copolymers that have clear prospects for petrochemical and biomedical applications. However, in contrast to the well-established polymerization of acrylate monomers, these processes have not been studied theoretically using the density functional theory (DFT) calculations. In our research, we performed a comprehensive theoretical analysis of the free radical copolymerization of MA and closely related maleimide with different structural types of olefins at mpw1pw91/6-311g(d) level of the DFT. The results of our calculations clearly indicated the preference of the alternating reaction mode for the copolymerization of MA with α-olefins, isobutylene and prospective unsaturated monomers, as well as methylenealkanes. The DFT modeling of the thermally induced Alder-ene reaction between MA and olefins allowed to exclude this reaction from the scope of possible side processes at moderately high temperatures. Comparative analysis of MA and N-methylmaleimide (MMI) reactivity shown that the use of MMI instead of MA makes no sense in terms of the reaction rate and selectivity.

| S-EPMC7240384 | biostudies-literature

Formal [2 + 2 + 2] cycloaddition strategy based on an intramolecular propargylic ene reaction/Diels-Alder cycloaddition cascade.

Project description:A formal, metal-free, [2 + 2 + 2] cycloaddition strategy is described based on a cascade of two pericyclic processes. The first step involves an intramolecular propargylic ene reaction of a 1,6-diyne to generate a vinylallene, which then reacts in an inter- or intramolecular Diels-Alder reaction with an alkenyl or alkynyl dienophile. Reactions involving unsymmetrical alkenyl and alkynyl dienophiles proceed with good to excellent regioselectivity, and the diastereoselectivity in the Diels-Alder step is also high, with endo cycloadducts produced as the exclusive products of the reaction. In the case of alkynyl dienophiles, [4 + 2] cycloaddition initially generates an isotoluene-type intermediate that isomerizes to the isolated aromatic product upon exposure to a catalytic amount of DBU at room temperature. The mechanism of several earlier fully intramolecular related transformations have been shown to involve an analogous process rather than the diradical-mediated pathways proposed previously.

| S-EPMC2924204 | biostudies-literature

The pentadehydro-Diels-Alder reaction.

Project description:In the classic Diels-Alder [4?+?2] cycloaddition reaction, the overall degree of unsaturation (or oxidation state) of the 4? (diene) and 2? (dienophile) pairs of reactants dictates the oxidation state of the newly formed six-membered carbocycle. For example, in the classic Diels-Alder reaction, butadiene and ethylene combine to produce cyclohexene. More recent developments include variants in which the number of hydrogen atoms in the reactant pair and in the resulting product is reduced by, for example, four in the tetradehydro-Diels-Alder (TDDA) and by six in the hexadehydro-Diels-Alder (HDDA) reactions. Any oxidation state higher than tetradehydro (that is, lacking more than four hydrogens) leads to the production of a reactive intermediate that is more highly oxidized than benzene. This increases the power of the overall process substantially, because trapping of the reactive intermediate can be used to increase the structural complexity of the final product in a controllable and versatile manner. Here we report an unprecedented overall 4??+?2? cycloaddition reaction that generates a different, highly reactive intermediate known as an ?,3-dehydrotoluene. This species is in the same oxidation state as a benzyne. Like benzynes, ?,3-dehydrotoluenes can be captured by various trapping agents to produce structurally diverse products that are complementary to those arising from the HDDA process. We call this new cycloisomerization process a pentadehydro-Diels-Alder (PDDA) reaction-a nomenclature chosen for chemical taxonomic reasons rather than mechanistic ones. In addition to alkynes, nitriles (RC?N), although non-participants in aza-HDDA reactions, readily function as the 2? component in PDDA cyclizations to produce, via trapping of the ?,3-(5-aza)dehydrotoluene intermediates, pyridine-containing products.

| S-EPMC4877333 | biostudies-literature

Photochemical Hexadehydro-Diels-Alder Reaction.

Project description:We demonstrate that the hexadehydro-Diels-Alder (HDDA) cycloisomerization reaction to produce reactive benzyne derivatives can be initiated photochemically. As with the thermal variant of the HDDA process, the reactive intermediates are formed in the absence of reagents or the resulting byproducts required for the generation of benzynes by traditional methods. This photo-HDDA (or hν-HDDA) reaction occurs at much lower temperatures (including even at -70 °C) than the thermal HDDA, but the benzynes produced behave in the same fashion with respect to their trapping reactions, suggesting they are of the same electronic state.

| S-EPMC6348472 | biostudies-literature

The hexadehydro-Diels-Alder reaction.

Project description:Arynes (aromatic systems containing, formally, a carbon-carbon triple bond) are among the most versatile of all reactive intermediates in organic chemistry. They can be 'trapped' to give products that are used as pharmaceuticals, agrochemicals, dyes, polymers and other fine chemicals. Here we explore a strategy that unites the de novo generation of benzynes-through a hexadehydro-Diels-Alder reaction-with their in situ elaboration into structurally complex benzenoid products. In the hexadehydro-Diels-Alder reaction, a 1,3-diyne is engaged in a [4+2] cycloisomerization with a 'diynophile' to produce the highly reactive benzyne intermediate. The reaction conditions for this simple, thermal transformation are notable for being free of metals and reagents. The subsequent and highly efficient trapping reactions increase the power of the overall process. Finally, we provide examples of how this de novo benzyne generation approach allows new modes of intrinsic reactivity to be revealed.

| S-EPMC3538845 | biostudies-literature

The aromatic ene reaction.

Project description:The ene reaction is a pericyclic process in which an alkene with an allylic hydrogen atom (the ene donor) reacts with a second unsaturated species (the enophile) to form a new product with a transposed ?-bond. The aromatic ene reaction, in which the alkene component is embedded in an aromatic ring, has only been reported in a few (four) instances and has proceeded in low yield (?6%). Here, we show efficient aromatic ene reactions in which a thermally generated aryne intermediate engages a pendant m-alkylarene substituent to produce a dearomatized isotoluene, itself another versatile but rare reactive intermediate. Our experiments were guided by computational studies that revealed structural features conducive to the aromatic ene process. We proceeded to identify a cascade comprising three reactions: (1) hexadehydro-Diels-Alder (for aryne generation), (2) intramolecular aromatic ene and (3) bimolecular Alder ene. The power of this cascade is evident from the structural complexity of the final products, the considerable scope, and the overall efficiency of these multistage, reagent- and by-product-free, single-pot transformations.

| S-EPMC4281267 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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