Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Chemoselective protection of alpha-ketoacids by direct annulations with oximes.

ABSTRACT: Oximes and alpha-ketoacids undergo an unexpectedly facile and chemoselective annulation to afford 2,5-dihydrooxazole 3-oxides. The resulting cyclic nitrones serve as chemically and configurationally stable masked alpha-ketoacids that can be easily elaborated and manipulated. Deprotection is achieved by mild reduction with zinc metal and hydrolysis. This methodology allows for the protection, elaboration, and deprotection of enantiopure peptide derived alpha-ketoacids, which are the key starting materials for the chemoselective ketoacid-hydroxylamine peptide ligation.

SUBMITTER: Flores MA

PROVIDER: S-EPMC2883889 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Chemoselective protection of alpha-ketoacids by direct annulations with oximes.

Flores Melissa A MA Bode Jeffrey W JW

Organic letters 20100501 9

Oximes and alpha-ketoacids undergo an unexpectedly facile and chemoselective annulation to afford 2,5-dihydrooxazole 3-oxides. The resulting cyclic nitrones serve as chemically and configurationally stable masked alpha-ketoacids that can be easily elaborated and manipulated. Deprotection is achieved by mild reduction with zinc metal and hydrolysis. This methodology allows for the protection, elaboration, and deprotection of enantiopure peptide derived alpha-ketoacids, which are the key starting ...[more]

PMID: 20356071

Similar Datasets

Unusually Chemoselective Photocyclization of 2-(Hydroxyimino)aldehydes to Cyclobutanol Oximes: Synthetic, Stereochemical, and Mechanistic Aspects.

Project description:Photocyclization of carbonyl compounds (known as the Norrish-Yang reaction) to yield cyclobutanols is, in general, accompanied by fragmentation reactions. The latter are predominant in the case of aldehydes so that secondary cyclobutanols are not considered accessible via the straightforward Norrish-Yang reaction. A noteworthy exception has been reported in our laboratory, where cyclobutanols bearing a secondary alcohol function were observed upon UV light irradiation of 2-(hydroxyimino)aldehydes (HIAs). This reaction is here investigated in detail by combining synthesis, spectroscopic data, molecular dynamics, and DFT calculations. The synthetic methodology is generally applicable to a series of HIAs, affording the corresponding cyclobutanol oximes (CBOs) chemoselectively (i.e., without sizable fragmentation side-reactions), diastereoselectively (up to >99:1), and in good to excellent yields (up to 95%). CBO oxime ether derivatives can be purified and diastereomers isolated by standard column chromatography. The mechanistic and stereochemical picture of this photocyclization reaction, as well as of the postcyclization E/Z isomerization of the oxime double bond is completed.

| S-EPMC9639046 | biostudies-literature

Branched chain α-ketoacids aerobically activate HIF1α signaling in vascular cells.

Project description:Hypoxia-inducible factor 1α (HIF1α) is a master regulator of numerous biological processes under low oxygen tensions. Yet, the mechanisms and biological consequences of aerobic HIF1α activation by intrinsic factors, particularly in primary cells remain elusive. Here, we show that HIF1α signaling is activated in several human primary vascular cells under ambient oxygen tensions, and in vascular smooth muscle cells (VSMCs) of normal human lung tissue, which contributed to a relative resistance to further enhancement of glycolytic activity in hypoxia. Mechanistically, aerobic HIFα activation is mediated by paracrine secretion of three branched chain α-ketoacids (BCKAs), which suppress prolyl hydroxylase domain-containing protein 2 (PHD2) activity via direct inhibition and via lactate dehydrogenase A (LDHA)-mediated generation of L-2-hydroxyglutarate (L2HG). Metabolic dysfunction induced by BCKAs was observed in the lungs of rats with pulmonary arterial hypertension (PAH) and in pulmonary artery smooth muscle cells (PASMCs) from idiopathic PAH patients. BCKA supplementation stimulated glycolytic activity and promoted a phenotypic switch to the synthetic phenotype in PASMCs of normal and PAH subjects. In summary, we identify BCKAs as novel signaling metabolites that activate HIF1α signaling in normoxia and that the BCKA-HIF1α pathway modulates VSMC function and may be relevant to pulmonary vascular pathobiology.

| S-EPMC11160772 | biostudies-literature

Palladium-catalyzed chemoselective direct α-arylation of carbonyl compounds with chloroaryl triflates at the C-Cl site.

Project description:This study described palladium-catalyzed chemoselective direct α-arylation of carbonyl compounds with chloroaryl triflates in the Ar-Cl bond. The Pd/SelectPhos system showed excellent chemoselectivity toward the Ar-Cl bond in the presence of the Ar-OTf bond with a broad substrate scope and excellent product yields. The electronic and steric hindrance offered by the -PR2 group of the ligand with the C2-alkyl group was found to be the key factor affecting the reactivity and chemoselectivity of the α-arylation reaction. The chemodivergent approach was also successfully employed in the synthesis of flurbiprofen and its derivatives (e.g., -OMe and -F).

| S-EPMC9067565 | biostudies-literature

Structural basis for the potent calpain inhibitory activity of peptidyl alpha-ketoacids.

Project description:A series of peptidyl alpha-ketoacids and alpha-ketoesters was synthesized and studied as mu-calpain inhibitors. Docking studies revealed that the mu-calpain inhibitory activity of the compounds is influenced by hydrogen bonding interactions and the potential for ionic interaction with active site residues as well as placement of a planar N-terminal capping group into the S 3 pocket of the enzyme.

| S-EPMC2643072 | biostudies-literature

Chemoselective α,β-Dehydrogenation of Saturated Amides.

Project description:We report a method for the selective α,β-dehydrogenation of amides in the presence of other carbonyl moieties under mild conditions. Our strategy relies on electrophilic activation coupled to in situ selective selenium-mediated dehydrogenation. The α,β-unsaturated products were obtained in moderate to excellent yields, and their synthetic versatility was demonstrated by a range of transformations. Mechanistic experiments suggest formation of an electrophilic SeIV species.

| S-EPMC6348382 | biostudies-literature

Branched-chain α-ketoacids are preferentially reaminated and activate protein synthesis in the heart.

Project description:Branched-chain amino acids (BCAA) and their cognate α-ketoacids (BCKA) are elevated in an array of cardiometabolic diseases. Here we demonstrate that the major metabolic fate of uniformly-13C-labeled α-ketoisovalerate ([U-13C]KIV) in the heart is reamination to valine. Activation of cardiac branched-chain α-ketoacid dehydrogenase (BCKDH) by treatment with the BCKDH kinase inhibitor, BT2, does not impede the strong flux of [U-13C]KIV to valine. Sequestration of BCAA and BCKA away from mitochondrial oxidation is likely due to low levels of expression of the mitochondrial BCAA transporter SLC25A44 in the heart, as its overexpression significantly lowers accumulation of [13C]-labeled valine from [U-13C]KIV. Finally, exposure of perfused hearts to levels of BCKA found in obese rats increases phosphorylation of the translational repressor 4E-BP1 as well as multiple proteins in the MEK-ERK pathway, leading to a doubling of total protein synthesis. These data suggest that elevated BCKA levels found in obesity may contribute to pathologic cardiac hypertrophy via chronic activation of protein synthesis.

| S-EPMC7960706 | biostudies-literature

Phosphine-Catalyzed Intramolecular Cyclizations of α-Nitroethylallenoates Forming (Z)-Furanone Oximes.

Project description:A novel and efficient phosphine-catalyzed intramolecular cyclization of α-nitroethylallenic esters is reported. This process appears to be practical for the stereoselective syntheses of (Z)-furan-2(3H)-one oxime derivatives in excellent yields. Mechanistically, the reaction involves a phosphine-catalyzed Michael addition of an alkylideneazinate and rearrangement of the cyclic nitronate to the α-nitrosodihydrofuran.

| S-EPMC4922534 | biostudies-literature

Chemoselective α-Sulfidation of Amides Using Sulfoxide Reagents.

Project description:The direct α-sulfidation of tertiary amides using sulfoxide reagents under electrophilic amide activation conditions is described. Employing convenient and readily available reagents, selective functionalization takes place to generate isolable sulfonium ions en route to α-sulfide amides. Mechanistic studies identified activated sulfoxides as promoters of the desired transformation and enabled the extension of the methodology from benzylic to aliphatic amide substrates.

| S-EPMC7680396 | biostudies-literature

A plausible metal-free ancestral analogue of the Krebs cycle composed entirely of α-ketoacids.

Project description:Efforts to decipher the prebiotic roots of metabolic pathways have focused on recapitulating modern biological transformations, with metals typically serving in place of cofactors and enzymes. Here we show that the reaction of glyoxylate with pyruvate under mild aqueous conditions produces a series of α-ketoacid analogues of the reductive citric acid cycle without the need for metals or enzyme catalysts. The transformations proceed in the same sequence as the reverse Krebs cycle, resembling a protometabolic pathway, with glyoxylate acting as both the carbon source and reducing agent. Furthermore, the α-ketoacid analogues provide a natural route for the synthesis of amino acids by transamination with glycine, paralleling the extant metabolic mechanisms and obviating the need for metal-catalysed abiotic reductive aminations. This emerging sequence of prebiotic reactions could have set the stage for the advent of increasingly sophisticated pathways operating under catalytic control.

| S-EPMC8570912 | biostudies-literature

Chemoselective Alpha-Deuteration of Amides via Retro-ene Reaction.

Project description:A synthetically convenient approach for the direct α-deuteration of amides is reported. This mechanistically unusual process relies on a retro-ene-type process, triggered by the addition of deuterated dimethyl sulfoxide to a keteniminium intermediate, generated through electrophilic amide activation. The transformation displays broad functional-group tolerance and high deuterium incorporation.

| S-EPMC7756638 | 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