Browse
Submit Data
Databases
API
Help

Dataset Information

7 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pd-Catalyzed Asymmetric N-Allylation of Amino Acid Esters with Exceptional Levels of Catalyst Control: Stereo-Divergent Synthesis of ProM-15 and Related Bicyclic Dipeptide Mimetics.

ABSTRACT: A general and powerful method for the stereo-controlled Pd-catalyzed N-allylation of amino acid esters is reported, as a previously largely unsolved synthetic challenge. Employing a new class of tartaric acid-derived C₂ -symmetric chiral diphosphane ligands the developed asymmetric amination protocol allows the conversion of various amino acid esters to the N-allylated products with highest levels of enantio- or diastereoselectivity in a fully catalyst-controlled fashion and predictable configuration. Remarkably, the in situ generated catalysts also exhibit outstanding levels of activity (ligand acceleration). The usefulness of the method was demonstrated in the stereo-divergent synthesis of a set of new conformationally defined dipeptide mimetics, which represent new modular building blocks for the development of peptide-inspired bioactive compounds.

SUBMITTER: Dohmen S

PROVIDER: S-EPMC7078984 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Synthesis and conformational analysis of bicyclic extended dipeptide surrogates.

Project description:Regio- and diastereoselective reactions of a homoproline enolate enable the synthesis of novel extended dipeptide surrogates. Bicyclic carbamate 9 and fused beta-lactam scaffold 11 were prepared from L-pyroglutamic acid via substrate-controlled electrophilic azidation. Synthesis of orthogonally protected hexahydropyrrolizine, hexahydropyrrolizinone, and hexahydropyrroloazepinone dipeptide surrogates relied on allylation of proline derivative 5, followed by Curtius rearrangement to introduce the N-terminal carbamate group. A total of six azabicycloalkane derivatives were evaluated for conformational mimicry of extended dipeptides by a combination of X-ray diffraction and molecular modeling. Analysis of putative backbone dihedral angles and N- to C-terminal dipeptide distances indicate that compounds (alpha'S)-14b and 21 approximate the conformation of dipeptides found in beta-sheets, while tripeptide mimic 28 is also highly extended in the solid state. Structural data suggest that ring size and relative stereochemistry have a profound effect on the ability of these scaffolds to act as beta-strand mimetics and should inform the design of related conformational probes.

| S-EPMC2914495 | biostudies-literature

Palladium-Catalyzed Allylation/Benzylation of H-Phosphinate Esters with Alcohols.

Project description:The Pd-catalyzed direct alkylation of H-phosphinic acids and hypophosphorous acid with allylic/benzylic alcohols has been described previously. Here, the extension of this methodology to H-phosphinate esters is presented. The new reaction appears general, although its scope is narrower than with the acids, and its mechanism is likely different. Various alcohols are examined in their reaction with phosphinylidene compounds R¹R²P(O)H.

| S-EPMC6273960 | biostudies-literature

Decarboxylative allylation of amino alkanoic acids and esters via dual catalysis.

Project description:A combination of photoredox and palladium catalysis has been employed to facilitate the room temperature decarboxylative allylation of recalcitrant ?-amino and phenylacetic allyl esters. This operationally simple process produces CO2 as the only byproduct and provides direct access to allylated alkanes. After photochemical oxidation, the carboxylate undergoes radical decarboxylation to site-specifically generate radical intermediates which undergo allylation. A radical dual catalysis mechanism is proposed. Free phenylacetic acids were also allylated utilizing similar reactions conditions.

| S-EPMC4183636 | biostudies-literature

Enantioselective <i>α</i>-Allylation of Aryl Acetic Acid Esters via C1-Ammonium Enolate Nucleophiles: Identification of a Broadly Effective Palladium Catalyst for Electron-Deficient Electrophiles.

Project description:We have identified a generally effective Pd catalyst for the highly enantioselective cooperative Lewis base/Pd-catalyzed α-allylation of aryl acetic esters using electron-deficient electrophiles. Changing between aldehyde, ketone, ester, and amide substituents at the terminus of intermediate cationic π-(allyl)Pd species affects both the efficiency of the reaction and, in the case of amides, control over the stereochemistry of the product alkene, as a function of the ligand. Tris[tri(2-thienyl)phosphino]Pd(0) serves as a broadly effective catalyst and overcomes these challenges to provide a general, high-yielding, and operationally simple C(sp3)-C(sp3) bond-forming method that gives products with high levels of enantioselectivity.

| S-EPMC6519469 | biostudies-literature

Divergent heparin oligosaccharide synthesis with preinstalled sulfate esters.

Project description:Traditional chemical synthesis of heparin oligosaccharides first involves assembly of the full length oligosaccharide backbone followed by sulfation. Herein, we report an alternative strategy in which the O-sulfate was introduced onto glycosyl building blocks as a trichloroethyl ester prior to assembly of the full length oligosaccharide. This allowed divergent preparation of both sulfated and non-sulfated building blocks from common advanced intermediates. The O-sulfate esters were found to be stable during glycosylation as well as typical synthetic manipulations encountered during heparin oligosaccharide synthesis. Furthermore, the presence of sulfate esters in both glycosyl donors and acceptors did not adversely affect the glycosylation yields, which enabled us to assemble multiple heparin oligosaccharides with preinstalled 6-O-sulfates.

| S-EPMC3324038 | biostudies-literature

Bicyclic β-Sheet Mimetics that Target the Transcriptional Coactivator β-Catenin and Inhibit Wnt Signaling.

Project description:Protein complexes are defined by the three-dimensional structure of participating binding partners. Knowledge about these structures can facilitate the design of peptidomimetics which have been applied for example, as inhibitors of protein-protein interactions (PPIs). Even though β-sheets participate widely in PPIs, they have only rarely served as the basis for peptidomimetic PPI inhibitors, in particular when addressing intracellular targets. Here, we present the structure-based design of β-sheet mimetics targeting the intracellular protein β-catenin, a central component of the Wnt signaling pathway. Based on a protein binding partner of β-catenin, a macrocyclic peptide was designed and its crystal structure in complex with β-catenin obtained. Using this structure, we designed a library of bicyclic β-sheet mimetics employing a late-stage diversification strategy. Several mimetics were identified that compete with transcription factor binding to β-catenin and inhibit Wnt signaling in cells. The presented design strategy can support the development of inhibitors for other β-sheet-mediated PPIs.

| S-EPMC8252567 | biostudies-literature

Zippered G-quadruplex/hemin DNAzyme: exceptional catalyst for universal bioanalytical applications.

Project description:G-quadruplex (G4)/hemin DNAzyme is promising horseradish peroxidase (HRP)-mimic candidate in the biological field. However, its relatively unsatisfactory catalytic capacity limits the potential applications. Inspired by nature protease, we conducted a proximity-enhanced cofactor assembly strategy (PECA) to form an exceptional HRP mimic, namely zippered G4/hemin DNAzyme (Z-G4/H). The hybridization of short oligonucleotides induced proximity assembly of the DNA-grafted hemin (DGH) with the complementary G4 sequences (cG4s), mimicking the tight configuration of protease cofactor and apoenzyme. The detailed investigations of catalytic efficiency and mechanism verified the higher activity, more rapid catalytic rate and high environmental tolerance of the Z-G4/H than the classical G4/hemin DNAzymes (C-G4/H). Furthermore, a proximity recognition transducer has been developed based on the PECA for sensitive detection of gene rearrangement and imaging human epidermal growth factor receptor 2 protein (HER2) dimerization on cell surfaces. Our studies demonstrate the high efficiency of Z-G4/H and its universal application potential in clinical diagnostics and biomolecule interaction research. It also may offer significant opportunities and inspiration for the engineering of the protease-free mimic enzyme.

| S-EPMC8682752 | biostudies-literature

Carbohydrate-Based Fat Mimetics Can Affect the Levels of 3-Monochloropropane-1,2-Diol Esters and Glycidyl Esters in Shortbread Biscuits.

Project description:Shortbread biscuits have become one of the most desirable snacks in all population groups but due to its high fat content it is searching for new solutions of fat reduction such as the use of carbohydrate-based fat mimetics. However, the thermal processing of food containing lipids in the presence of certain carbohydrates can contribute to the formation of toxic compounds or alter its levels. Therefore, the aim of the study was to evaluate the use of inulin and pectin gels as partial fat replacers (10-40%) in classical shortbread biscuits in a view of the changes of 3-monochloropropane-1,2-diol ester (3-MCPDE) and glycidyl ester (GE) levels after baking, and also after a two-months storage. The experiment showed that the amount of inulin gel higher than 10% promoted the endogenous formation of 3-MCPDE probably due to the higher amount of Maillard products formed in the biscuits, but after two months the levels decreased and were comparable with those transferred from shortening. Pectin did not demonstrate such phenomenon, owing to the presence of bound water in gel. Glycidyl esters were partially decomposed during baking and also during storage, particularly in the samples with the addition of pectin gel, which presumably caused by low stability of GE under acidic conditions resulting from the occurrence of galacturonic acid in pectin.

| S-EPMC6525143 | biostudies-literature

Annulation reactions of allenyl esters: an approach to bicyclic diones and medium-sized rings.

Project description:A flexible approach to construct sterically congested bicyclo-alkenedione frameworks is reported. Under the action of potassium carbonate, ?-sulphonyl cycloalkanones are added to functionalized allenyl esters, leading to a lactone intermediate that is subsequently reduced to initiate an intramolecular aldol cyclization to [3.2.1], [3.3.1], and [4.3.1] bicycles. Oxidation then affords bicyclic diones in good three-step yields. Under exceptionally mild conditions, these bicycles are converted to highly functionalized medium-sized rings through a Grob-type fragmentation.

| S-EPMC4184455 | biostudies-other

Elongation of 1,3-polyols via iterative catalyst-directed carbonyl allylation from the alcohol oxidation level.

Project description:Iterative enantioselective carbonyl allylation from the alcohol oxidation level under the conditions of iridium catalyzed transfer hydrogenation enables chain elongation of 1,3-polyols. High levels of catalyst-directed enantioselectivity and diastereoselectivity are observed.

| S-EPMC2720825 | 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