Keto Compounds Research Articles

Redox proteomics: Methods for the identification and enrichment of redox-modified proteins and their applications.

PTMs are defined as covalent additions to functional groups of amino acid residues in proteins like phosphorylation, glycosylation, S-nitrosylation, acetylation, methylation, lipidation, SUMOylation as well as oxidation. Oxidation of proteins has been characterized as a double-edged sword. While oxidative modifications, in particular of cysteine residues, are widely involved in the regulation of cellular homeostasis, oxidative stress resulting in the oxidation of biomolecules along with the disruption of their biological functions can be associated with the development of diseases, such as cancer, diabetes, and neurodegenerative diseases, respectively. This is also the case for advanced glycation end products, which result from chemical reactions of keto compounds such as oxidized sugars with proteins. The role of oxidative modifications under physiological and pathophysiological conditions remains largely unknown. Recently, novel technologies have been established that allow the enrichment, identification, and characterization of specific oxidative PTMs (oxPTMs). This is essential to develop strategies to prevent and treat diseases that are associated with oxidative stress. Therefore this review will focus on (i) the methods and technologies, which are currently applied for the detection, identification, and quantification of oxPTMs including the design of high throughput approaches and (ii) the analyses of oxPTMs related to physiological and pathological conditions.

Highly efficient Au hollow nanosphere catalyzed chemo-selective oxidation of alcohols

Micelles of poly(styrene-b-2-vinyl pyridine-b-ethylene oxide) (PS-PVP-PEO) with core–shell–corona structures have been used as a scaffold for the fabrication of gold (Au) hollow nanospheres of particle size 26±2nm using HAuCl4 and NaBH4 as metal precursor and reducing agent, respectively. The PS core acts as a template for hollow void, the PVP shell serves as reaction sites for inorganic precursors, and PEO corona stabilizes the composite particles. Under acidic conditions, the PVP shell domain becomes positively charged pyridinum-species that electrostatically interacts with negatively charged AuCl4− ions. On reduction of these composite particles and subsequent solvent extraction leads to the formation of Au hollow nanospheres. Various analytical tools such as powder X-ray diffraction (XRD), transmission electron microscope (TEM), thermogravimetric analyses (TG/DTA), dynamic light scattering of (DLS) have been employed to characterize the polymeric micelles and hollow nanoparticles. The TEM and XRD studies confirmed the formation of highly crystalline Au hollow nanospheres. The Au hollow nanosphere/H2O2 system efficiently catalyzes the chemoselective oxidation of allylic-type unsaturated alcohols into aldehydes and ketones under mild liquid-phase conditions. The versatility of present catalytic system for the oxidation of other substrates like aliphatic-, acylic-, aromatic-, and heteroaromatic alcohols to their respective keto compounds has also been reported.

Exploring Meerwein–Ponndorf–Verley Reduction Chemistry for Biomass Catalysis Using a First-Principles Approach

Liquid phase catalytic hydrogenation of decomposition products of sugar molecules is challenging, but essential to produce platform chemicals and green chemicals from biomass. The Meerwein–Ponndorf–Verley (MPV) reduction chemistry is an excellent choice for the hydrogenation of keto compounds. The energy landscapes for the liquid phase catalytic hydrogenation of ethyl levulinate (EL) and furfural (FF) by Sn(IV) and Zr(IV) zeolite-like catalytic sites utilizing the hydrogen atoms from an isopropanol (IPA) solvent are explored using quantum chemical methods. The computed apparent activation free energy for the catalytic hydrogenation of EL by a Sn(IV) zeolite-like catalyst model site is (21.9 kcal/mol), which is close to the Al(III)-isopropoxide catalyzed (20.7 kcal/mol) EL hydrogenation indicating the similar efficiency of the Sn(IV) zeolite-like catalyst compared with the Al(III) catalyst used in the traditional MPV reactions. The catalytic efficiency of metal isopropoxides for the catalytic hydrogenation of EL is computed to be Al(III) > Sn(IV) > Zr(IV) in IPA solution, in agreement with experiment. Calculations were also performed with furfuryl alcohol as the source for hydrogen for the conversion of EL to γ-valerolactone using the Sn(IV) catalytic site. The barrier (22.7 kcal/mol) suggests a hydrogenation using aromatic primary alcohol as a hydrogen donor and using a Sn(IV) catalyst is feasible. In terms of reaction mechanisms, an intramolecular hydride transfer through a six membered transition state was found to be the turnover controlling transition state of liquid phase catalytic hydrogenation of carbonyl compounds considered in this study.

Palladium-Catalyzed Intramolecular Oxidative Heck Cyclization and Its Application toward a Synthesis of (±)-β-Cuparenone Derivatives Supported by Computational Studies

A novel and efficient intramolecular oxidative cyclization of substituted homoallylic alcohols to form cyclic keto compounds under palladium-catalyzed conditions is described. The reaction has practical applications in the synthesis of sesquiterpenes. The mechanism of cyclization, the key step in the tandem reaction­, was analyzed by using density functional theory calculations.

Triton-B-Catalyzed, Efficient, Solvent-Free Synthesis of Benzopyrans

A convenient and microwave-promoted novel protocol for the syntheses of diverse kinds of substituted benzopyrans from the corresponding variety of substituted hydroxy acetophenones and keto compounds using benzyltrimethylammonium hydroxide (Triton-B) under solvent-free conditions has been developed. This protocol is mild and efficient than the other reported methods.

Metabolism of SO2 binding compounds by Oenococcus oeni during and after malolactic fermentation in white wine

Sulfur dioxide (SO2) is the key additive for the preservation of wines. Carbonyl and keto compounds in wine can bind to SO2 and decrease its efficacy, resulting in higher total SO2 requirements. Increased consumer demand for low sulfite and organic wines pose production challenges if SO2 binders have not been properly managed during vinification. Malolactic fermentation (MLF) has been known to reduce bound SO2 levels but detailed time course studies are not available. In this work, the kinetics of major SO2 binding compounds and malic acid were followed during MLF in wine with 12 commercially available strains of Oenococcus oeni. Pyruvic acid, acetaldehyde and α-ketoglutaric acid were degraded to various degrees by O. oeni, but galacturonic acid was not. At the time of malic acid depletion, percent degradation of pyruvate, α-ketoglutaric acid and acetaldehyde was 49%, 14% and 30%, respectively. During MLF, the decrease in average bound SO2 levels, as calculated from carbonyl metabolism, was 22%. The largest reduction in wine carbonyl content occurred in the week after completion of MLF and was 53% (107mg/L to 34mg/L) calculated as bound SO2. Prolonged activity of bacteria in the wines (up to 3weeks post malic acid depletion) resulted only in reduced additional reductions in bound SO2 levels.The results suggest that microbiological wine stabilization one week after malic acid depletion is an effective strategy for maximum removal of SO2 binders while reducing the risk of possible post-ML spoilage by O. oeni leading to the production acetic acid and biogenic amines.

ChemInform Abstract: A Straightforward Approach Towards Functionalized γ‐Hydroxy and Heterocyclic Amino Acids.

AbstractA chelated enolate derived from glycine ester (II) undergoes regioselective ring‐ opening with functionalized oxiranes to yield γ‐hydroxy acid derivatives which are easily oxidized to keto compounds.

An Unexpected Oxidation of Unactivated Methylene C–H Using DIB/TBHP Protocol

An in situ generated hypervalent iodine species, bis(tert-butylperoxy)iodobenzene, was used as a peroxy radical source for the oxidation of unreactive, remote, and isolated alkyl (cyclic or aliphatic) esters and amides to the corresponding keto compounds under very mild conditions.

Understanding the Reactivity of Acyl Anion Equivalents: The Epoxide Ring Opening Case

AbstractAcyl anion equivalents (umpolung) are the practitioner's first choice en route to 1,3‐hydroxy keto compounds from epoxides. Why? This investigation evaluates computationally and experimentally the reactivity of a near comprehensive range of acyl anion equivalents using epoxide ring opening as a test vehicle. Reactivity understanding, reactivity order, surprise failures in performance, along with unprecedented, but far from superior, reactivity of TosMIC is presented for the first time.

Synthesis, Structure Analysis and Antibacterial Activity of New Potent Sulfonamide Derivatives

Modification of sulfonamid drug using different principles of chemical reactions was investigated. These reactions involve the condensation of an amino group with triethyl orthoformate and dimethylformamide dimethyl acetal. Ability of sulfa to condense with active keto compounds, like ethyl pyruvate and piprazine carboxyaldehye was studied. Alkyation of sulfa with different chloro derivatives was also reported. The structure of the isolated compound was elucidated and confirmed using elemental analysis and spectral data. The bioactivity of the ob-tained compounds was investigated against different gram positive and gram negative bacteria. The study reveals that most of the modified drugs show high to moderate antibacterial activity.

Four novel spirooxazacamphorsultam derivatives

The chiral compounds (6aS,9S,10aR)-11,11-dimethyl-5,5-dioxo-2,3,8,9-tetrahydro-6H-6a,9-methanooxazaolo[2,3-i][2,1]benzisothiazol-10(7H)-one, C(12)H(17)NO(4)S, (1), (7aS,10S,11aR)-12,12-dimethyl-6,6-dioxo-3,4,9,10-tetrahydro-7H-7a,10-methano-2H-1,3-oxazino[2,3-i][2,1]benzisothiazol-11(8H)-one, C(13)H(19)NO(4)S, (2), (6aS,9S,10R,10aR)-11,11-dimethyl-5,5-dioxo-2,3,7,8,9,10-hexahydro-6H-6a,9-methanooxazolo[2,3-i][2,1]benzisothiazol-10-ol, C(12)H(19)NO(4)S, (3), and (7aS,10S,11R,11aR)-12,12-dimethyl-6,6-dioxo-3,4,8,9,10,11-hexahydro-7H-7a-methano-2H-[1,3]oxazino[2,3-i][2,1]benzisothiazol-11-ol, C(13)H(21)NO(4)S, (4), consist of a camphor core with a five-membered spirosultaoxazolidine or six-membered spirosultaoxazine, as both their keto and hydroxy derivatives. In each structure, the molecules are linked via hydrogen bonding to the sulfonyl O atoms, forming chains in the unit-cell b-axis direction. The chains interconnect via weak C-H...O interactions. The keto compounds have very similar packing but represent the highest melting [507-508 K for (1)] and lowest melting [457-458 K for (2)] solids.

ChemInform Abstract: A Simple and Efficient Thiocyanation of Indoles, Anilines and Keto Compounds Catalyzed by a Polystyrene Resin Amberlyst‐15.

AbstractAdvantages of the title procedure are the mild reaction conditions, the ease of product isolation, and the cheap and commercially available catalyst.

Experimental and Computational Studies on the Structural and Thermodynamic Properties of Two Sulfur Heterocyclic Keto Compounds

The present work reports the standard (p° = 0.1 MPa) molar enthalpies of formation in the gaseous phase of thioxanthone, (91.9 ± 2.4) kJ·mol−1, and tetrahydrothio-γ-pyrone, (−164.6 ± 2.0) kJ·mol−1, at T = 298.15 K, derived from their standard molar energies of combustion and standard molar enthalpies of sublimation, measured by rotating-bomb combustion calorimetry and by the vacuum drop microcalorimetric technique, respectively. For comparison purposes, we performed additional standard ab initio molecular orbital calculations, using the G3(MP2)//B3LYP composite procedure, which were used for the calculation of the enthalpies of several homodesmotic reactions, allowing us to extract the standard molar enthalpies of formation, in the gaseous phase, of the two heterocycles considered in this work. The calculated results are in excellent agreement with the experimental data. The three-dimensional structure of the crystal tetrahydrothio-γ-pyrone was also determined by X-ray crystallography.

A Simple and Efficient Thiocyanation of Indoles, Anilines and Keto Compounds Catalyzed by a Polystyrene Resin Amberlyst-15

Thiocyanation of various aromatic, heteroaromatic and enolizable ketone compounds has been achieved with ammonium thiocyanate in presence of polystyrene cation exchange resin, Amberlyst-15. All the reactions were carried out in acetonitrile at room temperature. Keywords: Indoles, amines, ketones, amberlyst-15, ammonium thiocyanate, pyrrole

Crystallization and preliminary crystallographic analysis of Gre2p, an NADP(+)-dependent alcohol dehydrogenase from Saccharomyces cerevisiae.

Gre2p [Genes de respuesta a estres (stress-response gene)] from Saccharomyces cerevisiae is a monomeric enzyme of 342 amino acids with a molecular weight of 38.1 kDa. The enzyme catalyses both the stereospecific reduction of keto compounds and the oxidation of various hydroxy compounds and alcohols by the simultaneous consumption of the cofactor NADPH and formation of NADP(+). Crystals of a Gre2p complex with NADP(+) were grown using PEG 8000 as a precipitant. They belong to the monoclinic space group P2(1). The current diffraction resolution is 3.2 A. In spite of the monomeric nature of Gre2p in solution, packing and self-rotation calculations revealed the existence of two Gre2p protomers per asymmetric unit related by a twofold noncrystallographic axis.

Biocatalytic asymmetric amination of carbonyl functional groups – a synthetic biology approach to organic chemistry

Transaminases catalyze amino transfer reactions from amino donors such as amino acids or amines to keto acids or ketones to give chiral amino acid or amines in optically pure form. alpha-Amino acid dehydrogenases catalyze the asymmetric reductive amination of alpha-keto acids using ammonia as amino donor to furnish L-amino acids. The distinct features and synthetic application of these two enzymes are reviewed in an effort to illustrate their promising and challenging aspects in serving as approaches to the direct asymmetric synthesis of optically pure amines from the corresponding keto compounds, a formidable problem in organic chemistry.

In this issue: Biotechnology Journal 10/2009

AbstractSynthetic biology – computational methodsKaznessis et al., Biotechnol. J. 2009, 4, 1392–1405Professor Yiannis Kaznessis from Minnesota (MN, USA) discusses how theoretical synthetic biology may liberate empiricism in biological sciences beyond the unaided human brain. Because synthetic biological systems are relatively small and largely independent of evolutionary contexts, they can be represented with mathematical models strongly founded on first principles of molecular biology and laws of statistical thermodynamics. This may then be plausibly used to explain in unambiguous, quantitative terms how biological phenotypic complexity emerges as a result of well‐defined biomolecular interactions. He presents SynBioSS, a publicly available software package which implements this mathematical formalism.Synthetic biology – practical applicationsMarner, Biotechnol. J. 2009, 4, 1406–1419Successful design of new biological paradigms requires integration of many scientific disciplines including (but not limited to) protein engineering, metabolic engineering, genomics, structural biology, chemical biology, systems biology, and bioinformatics. At the human level, it is therefore necessary to integrate all of these expertise, by building multi‐disciplinary teams that place as much emphasis on discovery as on rational design. This review by Wesley Marner from Madison (WI, USA) focuses on recent applications of synthetic biology principles in three areas: (i) the construction of artificial biomolecules and biomaterials; (ii) the synthesis of both fine and bulk chemicals (including biofuels); and (iii) the construction of "smart" biological systems that respond to the surrounding environment.Synthetic biology – biocatalysisZhu and Hua, Biotechnol. J. 2009, 4, 1420–1431Researchers from China describe chiral amines that are widely desired in the fine chemical and pharmaceutical industries and whose syntheses may one day be achieved economically through the tools of synthetic biology. The distinct features and synthetic application of two enzymes are reviewed in an effort to illustrate their promising and challenging aspects in serving as approaches to the direct asymmetric synthesis of optically pure amines from the corresponding keto compounds, a formidable problem in organic chemistry.

Tris-β-diketones and related keto derivatives for use as building blocks in supramolecular chemistry

The synthesis of three new tris-β-diketones and some derivatives is reported. In two cases facile alkaline hydrolysis of the diketone moieties yielded the corresponding keto compounds. These are readily functionalised to provide tripodal ligands.

High pressure base-catalyzed oligomerization of ketones

The base-catalyzed reaction between acrylamide and acetone is studied at various pressures. In the lower pressure range up to 300 MPa, a Baylis–Hillman adduct is produced in low yield. Under 900 MPa, viscous liquids are obtained which are shown to be oligomers of acetone resembling polyacetals. Acrylamide serves as a stabilizing end-capping agent. The reaction can be extended to other keto compounds. The oligomers produced in this way are not stable. The structure of the oligomers appears complex. The mechanism is supposed to involve the formation of the intermediate zwitterionic Baylis–Hillman species which would add to acetone followed by anionic propagation. Another possibility is an initial aldol reaction followed by oligomerization. Pressure would be a highly beneficial parameter promoting ionogenesis.

Directed Evolution of Aldolases

This chapter describes the directed evolution of aldolases. The detailed protocols for generating aldolases with new catalytic properties are presented. The gene encoding aldolase can be amplified using the standard polymerase chain reaction (PCR) from a genomic DNA preparation using the Qiagen kit and primers flanking the gene with engineered restriction sites. Purify the resulting fragment on an agarose gel, digest with appropriate restriction enzymes, and ligate into the expression vector. The ligation product can then be transformed into the appropriate E. coli cloning strain by electroporation. Gene disruption of a chromosomally encoded wild-type enzyme should be performed without prior cloning via recombination with linear DNA in recBCD -deficient E. coli strains. Substrates for the retroaldol reaction can be synthesized enzymatically from aldehyde and keto compounds using wild-type aldolase or advantageously evolved mutants. It is found that in these caged substrates, fluorogenic umbelliferone is released through β elimination from the primary or secondary carbonyl retro-aldol reaction product.