Nitrone Formation Research Articles

Formation and cycloaddition reactions of ferrocenyl nitrones

Ferrocenyl nitrones derived from aldehydes or oximes react with electron deficient alkenes to give ferrocenylisoxazolidines. 5-Methoxycarbonylisoxazolidines are further transformed to ferrocenyl-pyrrolidinones by reductive cleavage. The regio- and stereoselectivity of the reactions are discussed.

Diastereoselective cycloaddition of alkylidenecyclopropane nitrones from palladium(0)-catalyzed nucleophilic substitution of asymmetric 1-alkenylcyclopropyl esters by amino acids

The asymmetric construction of perhydropyrrolo[3,4- b]pyridine derivatives was performed by chemo- and regioselective formation of enantiopure alkylidenecyclopropane nitrones, followed by diastereoselective intramolecular 1,3-dipolar cycloaddition. The resulting spirocyclopropane isoxazolidines then underwent thermally induced regioselective ring expansion into optically active diazaheterocycles.

Studies on organophosphorus compounds 104 Reaction of carbanions derived from alkylphosphonates

AbstractStructural effect of substituents directly bonded to carbanions bearing a phosphonate moiety is examined. Nucleophilic addition of phosphonate carbanion to 1‐nitroalkene followed by subsequent reaction with chlorotrimethylsilane leads to a series of 2‐isoxazoline based on the formation of an alkene and silyl nitronate as a 1,3‐dipole. On the other hand, addition of carbanion derived from isocyanomethylphosphonate to nitroalkene with he formation of nitronate followed by intromolecular cyclization provides substituted phosphoryl pyrroles.

ChemInform Abstract: Formation of Functional Cyclic Nitrones via a New Reaction Intermediate, Nitrosoketene and Its Development for the Synthesis of Nonproteinogenic Amino Acids

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Peroxidase-catalyzed pro- versus antioxidant effects of 4-hydroxytamoxifen: enzyme specificity and biochemical sequelae.

Some studies have shown the potential relevance of the oxidation products of 4-hydroxytamoxifen (4OHTAM) in carcinogenesis. Other studies show 4OHTAM has antioxidant properties. We characterized the one-electron oxidative activation reactions of 4OHTAM and three other phenolics, 3-hydroxytamoxifen (3OHTAM), 1-(4-hydroxyphenyl)-1, 2-diphenylethene, and phenol (PhOH), catalyzed by myeloperoxidase (MPx), horseradish peroxidase (HRP), lactoperoxidase, mushroom tyrosinase, and nonenzymatic initiators in vitro under a variety of conditions and in cells. Differences in activation of the phenolics by the enzymes were directly compared using cis-parinaric acid (PnA)-loaded human serum albumin. All phenolics were substrates for the enzymes, but MPx only weakly activated 4OHTAM to its phenoxyl radical. In HL60 cells loaded metabolically with PnA so that effects on phospholipids could be monitored by HPLC with fluorescence detection, PhOH plus H2O2 caused massive oxidation across all phospholipid classes. 4OHTAM dose-dependently protected phosphatidylethanolamine, phosphatidylserine, and phosphatidylcholine against both H2O2-induced and normal metabolic oxidation. This suggested 4OHTAM is a poor substrate for intracellular MPx. In rat aorta smooth muscle cells loaded with PnA, 4OHTAM also protected against AMVN-induced peroxidation of those three phospholipids and sphingomyelin, whereas 3OHTAM did not. Spin trapping of glutathionyl radicals (GS*) with DMPO and quantifying the ESR-silent nitrone form of the GS-DMPO adduct by HPLC showed that neither 3OHTAM plus H2O2 nor 4OHTAM plus H2O2 caused a significant level of GSH oxidation with isolated MPx, nor did the latter in HL60 cells, whereas PhOH plus H2O2 was a potent source of GS* in both systems. Both 4OHTAM and 3OHTAM formed the nitrone adduct under cell-free conditions when activated with HRP. The data show that the substrate specificity of a given (myelo)peroxidase determines if a phenolic exerts pro- (through generation of reactive phenoxyl radicals) or antioxidant (through radical scavenging) properties in intracellular environments.

Synthesis of trans-2,3-dimethoxy-3- (phenylamino)flavanones and related compounds

trans-2,3-Dimethoxy-3-(phenylamino)flavanones (2), a new type of flavanone derivatives, are synthesized from flavanones or 2'-hydroxychalcones in two steps, the first one being a condensation with nitrosobenzenes (Ehrlich-Sachs reaction) and the second an oxidation with (diacetoxyiodo)benzene in methanol. Nitrone formation, an important side reaction of the Ehrlich-Sachs reaction, has also been exploited to synthesize 2 simply by use of an excess of nitrosobenzene in aqueous methanol. Syntheses of several analogues of 2 are also reported.Key words: trans-2,3-dimethoxy-3-(phenylamino)flavanones, 2'-hydroxychalcones, nitrosobenzenes, 3-(phenylamino)flavones, (diacetoxyiodo)benzene.

ChemInform Abstract: Formation of Nitrone in the Reaction of para‐Nitroso‐N,N‐ dimethylaniline with Tetracyanoethylene.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Formation of nitrone in the reaction ofpara-nitroso-N,N-dimethylaniline with tetracyanoethylene

para-Nitroso-N,N-dimethylaniline reacts with tetracyanoethylene to give [4-(dimethyl-amino)phenylimino]malononitrileN-oxide 1 (65%) in addition to [4-(dimethyl-amino)phenylimino]malononitrile 2 (17%). The structures of the products are confirmed by spectral data and chemical transformations.

Intramolecular cycloaddition of α-allyloxycarbonylnitrone bearing a chiral sugar auxiliary: A short-step synthesis of the N-terminal amino acid component of nikkomycin Bz

Heating 2,3:5,6- O-dicyclohexylidene-L-gulose oxime with methyl glyoxylate hemiacetal followed by treatment of the resulting mixture with allyl alcohols in the presence of catalytic amounts of titanium tetrachloride and molecular sieves 4A caused tandem nitrone formation, transesterification, E, Z-isomerization and diastereofacial selective intramolecular cycloaddition to provide stereocontrolled polycyclic compounds in one step. This method could be applied efficiently to synthesis of the N-terminal amino acid component of nikkomycin Bz.

Oxidation of N,N-benzylalkylamines to nitrones by Mo(VI) and W(VI) polyperoxo complexes

Oxidation of N,N-benzylalkylamines in chloroform by Mo(VI) and W(VI) polyperoxo complexes (PPC) of general formula Q + 3{PO 4[MO(O 2) 2] 4} 3− (Q + = onium ion) yield the corresponding nitrones as oxidized products quantitatively. Only in the case of N,N-benzylmethylamine the formation of nitrone is accompanied by 25% of benzaldoxime. Oxidation of N,N-benzyltertbutylamine and N,N-benzylisopropylamine follows second order kinetics. This finding does not disqualify the hypothesis that the reaction might occur by a rate determining nucleophilic attack of the amine onto the peroxide oxygens leading, through a Bartlett-type transition state, to the probable formation of the corresponding hydroxylamine, which then is converted to nitrone in a faster step. Under this respect PPC behavior seems related to that of the corresponding anionic monuclear oxidants Q +[MO(O 2) 2L] −) (L = anionic ligand). On the other hand PPC toward N,N-benzylmethylamine behave similar to neutral mononuclear oxidants, MO(O 2) 2L, since in both cases the formation of an oxidant-substrate association complex appears a probable event along the reaction coordinate. However, whereas for the neutral mononuclear oxidants this oxidant-substrate adduct seems to react further toward external amine molecules through a Bartlett-type transition state, for PPC such an adduct seems to evolve to products through unimolecular events akin enzymatic processes.

ChemInform Abstract: N‐Alkenyl Nitrone Dipolar Cycloaddition Routes to Piperidines and Indolizidines. Part 7. Hydroxylamine‐Alkyne Cyclizations. Formation of Cyclic Nitrones and Application to the Synthesis of the Proposed Structure for (.+‐.)‐Acacialactam.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A General Synthetic Procedure for N-Unsubstituted Isoxazolidines via Nitrone-Olefin Cycloaddition. Remarkable Catalytic Effect of Bu2SnO

Abstract The remarkable catalysis of Bu2SnO for nitrone formation in the nitrone-olefin cycloaddition reaction has been discovered, and has led to the development of a general method for the synthesis of N-unsubstituted isoxazolidine derivatives.

Initial Kinetic and Mechanistic Characterization of Escherichia coli Fumarase A

The protein encoded by the fumA gene in Escherichia coli is shown herein to be a highly efficient and specific catalyst of the fumarase reaction. In an investigation of 21 substrate analogs, this protein only had substantial activity as a hydro-lyase on fumarate, malate, acetylene dicarboxylate, fluorofumarate, and 2(S),3(S)-tartrate. The kcat and kcat/Km for the hydration of fumarate by this protein are 3100 s−1 and 5 × 106 mol−1 s−1, respectively. It is likely that one physiological role of this protein is a catalyst of the fumarase reaction; therefore, it is appropriate to name it fumarase A. Fumarase A specifically removes the 3-pro-R in the dehydration of (2S)-malate. The product of the action of fumarase A on acetylene dicarboxylate, fluorofumarate and 2(S),3(S)-tartrate is oxalacetate. The nitronate form of 2-hydroxy-3-nitro-propionate is a potent inhibitor of fumarase A, implying that the enzyme forms an intermediate with an anion at C-3. No kinetic isotope effect was found with (2S,3R)-3-[2H]malate. The effects of pH on the kcat and kcat/Km for fumarate as a substrate show that the pKas of the groups involved in catalysis differ markedly from porcine fumarase. The possible roles of the proteins encoded by the three fumarase genes in E. coli are briefly discussed.

N-alkenyl nitrone dipolar cycloaddition routes to piperidines and indolizidines. Part 7. Hydroxylamine–alkyne cyclisations. Formation of cyclic nitrones and application to the synthesis of the proposed structure for (±)-acacialactam

The cyclisation of the alkynylhydroxylamines 2, 13, 14, 19, 27, 34, 39, 46 and 47 to give five-, six- and seven-membered cyclic nitrones is described. A concerted intramolecular ene-like pathway is proposed for the addition of the N–O–H group across the triple bond. Using the nitrone 48 as the starting material, the seven-membered lactam structure 49 proposed for the natural product acacialactam was prepared and was found to be incorrect.

ChemInform Abstract: Halogen‐Induced Formation of Nitrones from Oximes and Alkenes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A Herbicidal Inhibitor of Isopropylmalate Isomerase

Nitronate compounds resembling the aci-carboxylate reaction intermediate in the reaction catalyzed by isopropylmalate isomerase were investigated as enzyme inhibitors and potential herbicides. The nitronic acids of 1-hydroxy-2-nitrocyclopentane-1-carboxylic acid, nitroisopropylmalate and of 1-hydroxy -2-nitrocyclohexane-1-carboxylic acid were all potent inhibitors of isopropylmalate isomerase. The nitroalkane/nitronate pK a values of these were 7.3, 9.5 and 11.1, respectively. The perturbed pK a values of the first and last compound were und erstandable on the basis of the opposing effects of 5- and 6-membered ring strain on the ionization of the nitro group. As the only compound significantly in the nitronate form at physiological pH , it was not surprising that 1-hydroxy-2-nitrocyclopentane-1-carboxylic acid was the best herbicide. Its specific mode of action was confirmed by the fact that 1-hydroxy-2-nitrocyclopentane- 1-carboxylic acid inhibited the growth of carrot cells in liquid culture and was specifically reversed by leucine.

A synthesis of (−) supinidine and its regioisomer by intramolecular oxime olefin cycloaddition.

A synthesis of (−) supinidine 1 and its regioisomer 2 from L-proline is described. The key step is a thermal intramolecular oxime-olefin cycloaddition; dimerization products resulting from intramolecular nitrone formation were also isolated.

ChemInform Abstract: Phenylselenyl Halide Induced Formation of Cyclic Nitrones from Alkenyl Oximes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Cycloaddition reactions of carbohydrate derivatives. Part IV. Synthesis of a tetrahydroxyindolizidine through a cyclic nitrone prepared from D-xylose.

Intramolecular conjugate addition of the oxime from aldehyde 5 led to the formation of cyclic nitrone 6. 1,3-Dipolar cycloaddition of the latter with methyl acrylate gave the bicyclic 7 with high diastereoselection. Subsequent four-step transformation of 7 resulted in the tetrahydroxyindolizidine derivative 11.

ChemInform Abstract: Mercuric Acetate Induced Formation of Cyclic Nitrones from Alkenyl Oximes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.