Oxidative Coupling Of Phenols Research Articles

Oxidative phenol coupling—tyrosine dimers and libraries containing tyrosyl peptide dimers

The principles of phenol oxidation are outlined and summarized. Various procedures were used to dimerize tyrosine derivatives, especially linear tripeptides and cyclohexapeptides, via cross-linking of their phenolic side-chains. The coupling was performed by potassium hexacyanoferrate(III), phenyliodine(III)-bis(trifluoroacetate), vanadium(V)-oxyfluoride or horseradish peroxidase. The individual dityrosine and isodityrosine derivatives obtained in preparative scale, as well as the peptide-dimer libraries generated, were characterized by HPLC and electrospray ionization mass spectrometry. Further analyses were carried out by NMR spectroscopy, fluorescence spectroscopy and gas chromatography.

Catalytic aerobic oxidative coupling of some simple phenols and natural phenanthrols with CuCI(OH).TMEDA

Catalytic aerobic oxidative coupling of some simple phenols and natural phenanthrols with CuCI(OH).TMEDA

Synthesis of the bis-diaryl ether fragment of vancomycin via enzymatic oxidative phenolic coupling

The bis-diaryl ether cross-linked amino acid fragment, which constitutes the upper part of a vancomycin aglycone framework, was synthesized for the first time using an enzymatic oxidative phenolic coupling methodology. This was achieved via two peroxidase-catalyzed reactions of three amino acid derivatives, 2, 3a, and 4. Other C–O and C–C hetero and homo coupling products were also obtained.

Peroxidase-Catalyzed Oxidative Phenolic Coupling of Some Tripeptides Containing Tyrosine and Hydroxyphenylglycine Residues

Several tripeptides containing tyrosine or its mono or dichloro derivative; glycine; and 4-hydroxyphenylglycine or its monochloro derivative were prepared. They were subjected to horseradish peroxidase (HRP)-catalyzed oxidative phenolic coupling. Only the products of intermolecular reaction, primarily C-O and C-C coupled dimers, were obtained.

Development of intramolecular oxidative phenolic coupling reactions using hypervalent iodine (III) reagents and their application to the synthesis of Amaryllidaceae alkaloids

Hypervalent iodine (III) reagents nowadays are used extensively in the field of organic chemistry. Especially, phenyliodine (III) diacetate (PIDA) or phenyliodine (III) bis(trifluoroacetate) (PIFA) have received much attention because of their reactivities similar to heavy metal reagents or anodic oxidation, low toxicity, ready availability and easy handling. In the continuous study of our oxidative phenolic coupling reactions using a hypervalent iodine (III) reagents, a versatile synthetic procedure for the galanthamine-type Amaryllidaceae alkaloids was accomplished. The first total synthesis of (+/-)-sanguinine and the total syntheses of (+/-)-galanthamine, (+/-)-narwedine, (+/-)-lycoramine, and (+/-)-norgalanthamine were also successfully carried out.

Development of a Pilot Scale Process for the Anti-Alzheimer Drug (−)-Galanthamine Using Large-Scale Phenolic Oxidative Coupling and Crystallisation-Induced Chiral Conversion

(−)-Galanthamine has been synthesised using an efficient nine-step procedure, which in large scale affords 12.4 (6.7−19.1)% overall yield. The process improvements and optimization of each step are described. Notable steps include (i) an oxidative phenol coupling and (ii) crystallisation-induced chiral conversion of (±)-narwedine to (−)-narwedine. This is a practical and cost-effective synthesis of (−)-galanthamine which is amenable to pilot plant scale-up to afford sufficient material for use in clinical trials.

ChemInform Abstract: Natural Products by Oxidative Phenolic Coupling — Phytochemistry, Biosynthesis, and Synthesis

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 plausible mechanism for copper-catalyzed oxidative chlorophenol coupling reactions. Semi-empirical AM1 and ab initio 3-21G molecular orbital studies

Semi-empirical AM1 and ab initio molecular orbital calculations were performed to gain more insight into the mechanism of copper-catalyzed oxidative phenol coupling reactions. Partial charges were determined for chlorophenols, chlorophenolate anions, chlorophenoxy radicals and chlorophenoxonium cations (in both the singlet and triplet states) at the AM1 level. Calculations of these species indicate that the only aromatic carbon bearing a substantial positive charge is the para carbon of the cation in the singlet state. The results support a mechanism for copper-catalyzed oxidative phenol coupling in which dinuclear phenolate-bridged copper(II) species act as intermediates affording chlorophenoxonium cations after a double-bond one-electron transfer.

Aerobic catalytic oxidative coupling of 2-naphthols and phenols by VO(acac)2

In the presence of a catalytic amount of VO(acac)2, oxidative coupling of 2-naphthol or phenol derivatives with molecular oxygen occurred at room temperature and selectively gave the corresponding ortho–ortho coupling products in moderate to high yields.

First synthesis of mastigophorenes A and B, by biomimetic oxidative coupling of herbertenediol

The first synthesis of mastigophorenes A and B by oxidative phenolic coupling of partially protected derivatives of their joint natural monomeric half, herbertenediol, is described. The synthesis starts from this diol itself or from the corresponding aldehyde, both available by isolation from the liverwort, Herbertus aduncus. After transformation of herbertenediol to a chemically appropriate monophenolic coupling precursor, the oxidative dehydrodimerization was brought about using ( tert-BuO) 2, followed by deprotection to give mastigophorenes A and B in their ‘natural’ atropisomeric ratio, as isolated from the liverwort.

Enzymatic oxidative coupling of monohalogenated tyrosine derivatives

The regioselectivity of peroxidase-catalyzed oxidative phenolic coupling of monohalogenated tyrosine derivatives could be altered by the halogen substituent and the enzyme-substrate ratio. This ability to shift the coupling pattern (CC vs. CO) provides chemists with added versatility for synthetic applications.

Enzyme-catalyzed polymerization of 8-hydroxyquinoline-5-sulfonate byin situ nuclear magnetic resonance spectroscopy

In this report, we describe the use of in situ NMR spectroscopy to elucidate the mechanism of horseradish peroxidase-catalyzed oxidative free-radical coupling of phenols. We demonstrate the potential of the technique for the polymerization of 8-hydroxyquinoline-5-sulfonate (HQS). Based on the structural changes, we establish the involvement of ortho- and para-position protons (to the hydroxyl group) in the oxidative free-radical coupling polymerization with their relative preferences. For example, in HQS, we establish that the positions 2, 4, and 7 are involved in the chemical bonding with the order of preference being 7 ≥ 2 > 4. Analyses of 13 C-NMR data suggest the formation of C-C- and C-O-C-type coupling bonds during enzymatic polymerization.

Biosynthesis of the amaryllidaceae alkaloid Galanthamine

Application of radioactively as well as 13C-labelled 4′- O-methylnorbelladine to organs of field grown Leucojum aestivum plants resulted in an optimal incorporation into galanthamine (27%), and N-demethylgalanthamine (31%), respectively. In contrast to expectations based on results from the literature, the N-methylated 4′- O-methylnorbelladine was metabolized into a minor extent in L.aestivum and was incorporated into galanthamine as well as into N-demethylgalanthamine to only about 1\\3 of the rate of 4′- O-methylnorbelladine. Furthermore, it was shown that N-demethylgalanthamine is N-methylated to galanthamine in the final step of biosynthesis. A revised scheme for the biosynthesis of galanthamine is presented involving the phenol oxidative coupling of 4′- O-methylnorbelladine to a postulated dienone which undergoes spontaneous closure of the ether bridge to yield N-demethylnarwedine which upon stereoselective reduction and N-methylation yields the cholineesterase inhibitor galanthamine.

Chlorinated Diphenoquinones: A New Class of Dioxin Isomeric Compounds Discovered in Fly Ashes, Slags, and Pyrolysis Oil Samples by Using HPLC/ELCD and HRGC/MS

Chlorinated 4,4‘-diphenoquinones, previously unknown byproducts of thermal processes in the presence of chlorine, have been discovered in a variety of samples such as oil products from a waste pyrolysis plant, a fly ash from a municipal waste incinerator, and a sample of Kieselrot slag. The pyrolysis plant products also contained tetramethylated and unsubstituted 4,4‘-diphenoquinone. All compounds may be generated by oxidative coupling of phenols at elevated temperaturesa reaction that is considered to compete with the formation of the structurally isomeric dioxins. Once built-up, 4,4‘-diphenoquinones form a redox pair with the corresponding 4,4‘-dihydroxybiphenyls, with variable equilibrium positions depending on the prevailing conditions. For analysis, a cleanup method which involves liquid/liquid partition and solid-phase extraction was developed. The method is suitable for the determination of all substances of this class. Quantitative analysis was carried out by HPLC using an electrochemical detector...

Enantioselective synthesis of a benzofuranic neolignan by oxidative coupling

The first stereoselective free radical coupling of a phenylpropenoidic phenolic compound is reported. The oxidation of a chiral ferulic acid amide to give dimeric benzofuranic neolignan is performed enzymatically using horseradish peroxidase as the catalyst. Enantiomeric excess in a biologically active compound with phenylcoumaran skeleton (β-5 dimer) is thus obtained. The HRP-catalyzed enantioselective oxidative phenol coupling of a ferulic acid amide is reported. Ethyl-S-alaninate is the chiral auxiliary.

ChemInform Abstract: Enzymatic Oxidative Phenolic Coupling.

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.

Oxidative coupling of 4-substituted 2-methoxy phenols using methyltributylammonium permanganate in dichloromethane

Dimers of 4-substituted 2-methoxy phenols were prepared using methyltributylammonium permanganate (MTBAP) in dichloromethane. This methodology allows the selective coupling of such compounds preserving other moieties easily oxidized by permanganate anion in aqueous solution.

The biosynthesis of lunarine in seeds of Lunaria annua

Using an optimized precursor feeding system, the biosynthesis of the alkaloid lunarine in Lunaria annua seeds was investigated. The synthesis of radioactively labelled precursors for the application experiments is described. Lunarine was shown to be synthesized by stereo-selective phenol-oxidative coupling of N 1, N 10-bis( p-coumaroyl)spermidine. p-Coumaric acid for the biosynthesis of this dimer is formed from l-phenylalanine via trans-cinnamic acid. The polyamine moiety of lunarine, spermidine, and its immediate precursor putrescine are preferentially synthesized from arginine. Enzyme studies with microsomes of Lunaria annua seeds indicated that a cytochrome P-450 enzyme might be responsible for the phenol-oxidative coupling of N 1, N 10-bis ( p-coumaroyl)spermidine yielding the hexahydrodibenzofuran ring of lunarine.

First synthesis of the antimalarial naphthylisoquinoline alkaloid dioncophylline C, and its unnatural anti-HIV dimer, jozimine C

The first total synthesis of dioncophylline C, a new antimalarial lead structure, is described. For the directed construction of the stereogenic biaryl axis, the ‘lactone methodology’ is applied, despite the lack of a ‘bridgehead oxygen’ function in the target molecule. Furthermore, the novel dimer of dioncophylline C, ‘jozimine C’, is prepared, by oxidative phenolic coupling of the protected natural monomer. Jozimine C displays good antimalarial activity ( Plasmodium falciparum; IC 50 = 0.445 μg/ml), and, in particular, represents the first unnatural dimer of a naphthylisoquinoline alkaloid with a high anti-HIV activity (HIV-1; EC 50 = 27 μg/ml).

Biosynthesis. Part 27.1,2 Colchicine: studies of the phenolic oxidative coupling and ring-expansion processes based on incorporation of multiply labelled 1-phenethylisoquinolines

Earlier research from our group had proved that the biosynthesis of colchicine and its tropolonoid relatives involves the oxidative ring-closure of a 1-phenethyltetrahydroisoquinoline, autumnaline, followed by extensive modification of the cyclised product. These steps pose many mechanistic and stereochemical questions which are set out in the Introduction. The sequel then provides the answers based on the results from a series of incorporation experiments on Colchicum plants involving multiply labelled forms of autumnaline and its biological precursors. These multiply labelled samples required the synthesis of eleven differently labelled tetrahydroisoquinolines; the methods used to introduce the labels are described. Autumnaline is shown to be present in Colchicumautumnale plants and labelled forms of some precursors of it are synthesised and studied. Taken together, the findings allow further definition of a substantial part of the biosynthetic pathway to colchicine and its relatives.