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Glucosinolate turnover in Brassicales species to an oxazolidin-2-one, formed via the 2-thione and without formation of thioamide

Glucosinolates are found in plants of the order Brassicales and hydrolyzed to different breakdown products, particularly after tissue damage. In Barbarea vulgaris R.Br. (Brassicaceae), the dominant glucosinolate in the investigated ?G-type? is glucobarbarin, (S)-2-hydroxy-2-phenylethylglucosinolate. Formation of the nitrile from glucobarbarin was observed in vitro, while a previously suggested thioamide (synonym thionamide) was not confirmed. Resedine (5-phenyl-1,3-oxazolidin-2-one) was detected after glucobarbarin hydrolysis in crushed B. vulgaris leaves and siliques, but not in intact parts. The abundance increased for several hours after completion of hydrolysis. The corresponding 1,3-oxazolidine-2-thione (OAT), with the common name barbarin, was also formed, and appeared to be the precursor of resedine. Addition of each of two non-endogenous OATs, (S)-5-ethyl-5-methylOAT and (R)-5-vinylOAT (R-goitrin), to a leaf homogenate resulted in formation of the corresponding 1,3-oxazolidin-2-ones (OAOs), confirming the metabolic connection of OAT to OAO. Formation of OAOs was inhibited by prior brief heating of the homogenate, suggesting enzyme involvement. We suggest the conversion of OATs to OAOs to be catalyzed by an enzyme (?oxazolidinethionase?) responsible for turnover of OAT formed in intact plants. Resedine had been reported as an alkaloid from another species – Reseda luteola L. (Resedaceae) – naturally containing the glucosinolate glucobarbarin. However, resedine was not detected in intact R. luteola plants, but formed after tissue damage. The formation of resedine in two families suggests a broad distribution of putative OATases in the Brassicales; potentially involved in glucosinolate turnover that needs myrosinase activity as the committed step. In agreement with the proposed function of OATase, several candidate genes for myrosinases in glucosinolate turnover in intact plants were discovered in the B. vulgaris genome. We also suggest that biotechnological conversion of OATs to OAOs might improve the nutritional value of Brassicales protein. HPLC-MS/MS methods for detection of these glucobarbarin products are described.

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Methods of inhibiting and treating biofilms using glycopeptide antibiotics

The present invention is directed to methods of inhibition, delay of formation, treatment, prophylaxis and/or prevention of infections caused by bacteria that exhibit tolerance to antimicrobial agents, including slow growing, stationary-phase and biofilm forming bacteria, through the use of glycopeptide antibiotics, such as oritavancin.

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Copper-catalyzed carboarylation of alkynes via vinyl cations

Copper-catalyzed arylation of electron rich alkynes reveals stabilized trisubstituted vinyl cation equivalents that react with pendant arene nucleophiles to form all carbon tetrasubstituted alkenes. The new process streamlines the synthesis of important medicinally relevant molecules.

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(S)-4-isopropyl-5,5-diphenyloxazolidin-2-one

(S)-4-Isopropyl-5,5-diphenyloxazolidin-2-one has been synthesized for the first time by the enantiospecific oxidative carbonylation of commercially available (S)-2-amino-3-methyl-1, 1-diphenylbutan-1-ol. The cyclocarbonylation reaction was carried out at 100?C in 1,2-dimethoxyethane (DME) as the solvent for 15 h, under 20 atm of a 4:1 mixture of CO?air and in the presence of the catalytic system PdI2/KI (substrate:KI:PdI2 molar ratio = 100:10:1), to give the oxazolidinone derivative in 81% isolated yield.

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Dendritic bis(oxazoline)copper(II) catalysts. 2. Synthesis, reactivity, and substrate selectivity

A series of dendritic bis(oxazoline) ligands 1-4 were synthesized to evaluate the effects of the degree of branching of a dendritic sector on both the reactivity and selectivity of their corresponding copper(II) complex- catalyzed Diels-Alder reaction between cyclopentadiene and a crotonyl imide. Kinetic studies unveiled a two-step mechanism of the Diels-Alder reaction, in which a reversible binding of the dienophile to the copper complex was followed by a rate-determining reaction between the resulting dienophile- catalyst complex with the diene. Furthermore, two interesting features emerged: first, the formation constant of the dienophile-catalyst complex decreased gradually on going from the lower to higher generations, and secondly, while the Diels-Alder reaction rate constant remained essentially the same from the zeroth to second generation catalysts, it dropped abruptly for the third generation one. These observations were rationalized as a consequence of a folding-back of the dendritic sectors toward the catalytic unit at the third generation, so that increase in steric size impeded both the reactivity and binding profiles of the catalytic system. This behavior was reminiscent of related phenomena observed by others from solvatomatic, photophysical, and viscosity studies. In line with this reasoning, a slight but noticeable substrate selectivity was observed for the third generation catalyst, which was absence for the lower ones, in competitive kinetic studies involving two dienophiles of different steric sizes.

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Compound design guidelines for evading the efflux and permeation barriers of Escherichia coli with the oxazolidinone class of antibacterials: Test case for a general approach to improving whole cell Gram-negative activity

Previously we reported the results from an effort to improve Gram-negative antibacterial activity in the oxazolidinone class of antibiotics via a systematic medicinal chemistry campaign focused entirely on C-ring modifications. In that series we set about testing if the efflux and permeation barriers intrinsic to the outer membrane of Escherichia coli could be rationally overcome by designing analogs to reside in specific property limits associated with Gram-negative activity: i) low MW (<400), ii) high polarity (clogD7.4 <1), and iii) zwitterionic character at pH 7.4. Indeed, we observed that only analogs residing within these limits were able to overcome these barriers. Herein we report the results from a parallel effort where we explored structural changes throughout all three rings in the scaffold for the same purpose. Compounds were tested against a diagnostic MIC panel of Escherichia coli and Staphylococcus aureus strains to determine the impact of combining structural modifications in overcoming the OM barriers and in bridging the potency gap between the species. The results demonstrated that distributing the charge-carrying moieties across two rings was also beneficial for avoidance of the outer membrane barriers. Importantly, analysis of the structure-permeation relationship (SPR) obtained from this and the prior study indicated that in addition to MW, polarity, and zwitterionic character, having ?4 rotatable bonds is also associated with evasion of the OM barriers. These combined results provide the medicinal chemist with a framework and strategy for overcoming the OM barriers in GNB in antibacterial drug discovery efforts. Balanced chemical reaction does not necessarily reveal either the individual elementary reactions by which a reaction occurs or its rate law.Electric Literature of 497-25-6. In my other articles, you can also check out more blogs about 497-25-6

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Platinum-catalyzed intermolecular hydroamination of vinyl arenes with carboxamides

(Chemical Equation Presented) Reaction of benzamide with 4-methylstyrene catalyzed by a 1:2 mixture of [PtCl2(H2C=CH 2)]2 and P(4-C6H4CF 3)3 (5 mol %) in mesitylene at 140 C for 24 h led to the isolation of N-(1-p-tolylethyl)benzamide in 85% yield. Electron-rich, electron-poor, and hindered vinyl arenes underwent Markovnikov hydroamination with a range of carboxamides and amide derivatives in moderate to good yield with excellent regioselectivity.

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The high selectivity of the Cp2ZrHCl reducing agent for imides: A combined experimental and theoretical study on gamma-lactam and isoxazolidinone derivatives

Selective reductions of semicyclic imides either to hemiaminals (endo carbonyl reduction) or to aldehydes and amines (exo carbonyl reduction) in high yields by Schwartz’s reagent (Cp2ZrHCl) are reported. Mechanistic aspects of these reactions have been investigated at the DFT ab initio level with consideration of implicit solvent effects and thermal and pressure corrections to 298 K/1 atm. The reactions proceed from the reagents to very stable final Zr-oxo intermediates through the formation of sigma complexes and subsequent four-center transition state structures (1,2-migratory insertion). The energetic barriers for the insertion steps depend strongly on the natures of the ancillary groups at the reducing carbonyl groups. N-Carbamoyl groups are reduced to hemiaminals whereas N-acyl groups react at the exo carbonyl groups. The absence of the second carbonyl group in the simple N-methyl-2-pyrrolidone (less oxidized system) strongly reduces the thermodynamic drive for the formation of the metallocene oxo intermediate and allows an explanation of the remarkable chemoselectivity of the hydrozirconation. The zirconocene-oxo intermediates hydrolyze quickly throughout an ionic mechanism in which water molecules strongly assist the process by stabilizing ion pair separation. The computational results are consistent with a large set of experimental data on reduction of gamma-lactam and isoxazolidinone derivatives under mild conditions. They provide a way to explain and predict the relative importance of the two competitive endo/exo reduction channels of semicyclic imides by considering the electronic and steric features of substituents. Semicyclic imides such as gamma-lactam and isoxazolidinone derivatives are efficiently and selectivity reduced by the Cp2ZrHCl agent. The energetic reaction pathways for endo and exo attack, computed at the DFT level including thermal effects, allow an exhaustive interpretation of current and previously reported experimental data. Copyright

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Preparation and Complex Formation of Polymers Anchoring 2-Oxazolidinone

Polymers anchoring 3-unsubstituted 2-oxazolidinone were prepared and their complex formation with phenol and mercury(II) acetate were investigated.Preformed poly(4-hydroxystyrene) was treated with tris(2,3-epoxypropyl)isocyanurate to give a polymer containing 2-oxazolidinone residues within the limits of 57.7 molpercent.Polymers carrying 2-oxazolidinone were also prepared through the homopolymerization and copolymerization of 4-(2-oxo-5-oxazolidinylmethoxy)phenyl acrylate.The effective concentration of 2-oxazolidinone residue in the polymers, which is accessible to phenol, was determined on the assumption that the polymer-bound 2-oxazolidinone and phenol formed a 1:1 complex. 2-Oxazolidinone and a mercury atom formed a 2:1 complex; this relation on the molar ratio applies to all forms of complexes between the mercury atom and the 2-oxazolidinone residue in the polymers.

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Synthesis of cyclic carbonates from urea and diols over metal oxides

Several metal oxides were used for synthesis of ethylene carbonate from urea and ethylene glycol. ZnO showed high activity towards the reaction. TPD, FTIR and reaction test indicated that the catalysts with appropriate acid and base properties were favorable to the synthesis of cyclic carbonate. Furthermore, the reaction of urea with various diols revealed that the selectivity of five-membered cyclic carbonates was higher than that of six-membered cyclic carbonates.

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