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3,4-Disubstituted 6,7-indolequinones [1,3-dimethyl-4-(3‘-methylindol-2‘-yl)indole-6,7-dione (2), 3-methyl-4-phenylindole-6,7-dione (3), and 3,4-dimethyl-6,7-dione (4)] and a 3,7-disubstituted 4,5-indolequinone [3,7-dimethylindole-4,5-dione (5)] have been synthesized as models for the novel organic cofactor TTQ of bacterial amine dehydrogenases. The substituent and structural effects on the physicochemical properties of the quinones have been investigated in detail by comparing the spectroscopic data (UV−vis, IR, 1H- and 13C-NMR), pKa values of the pyrrole proton, and the two-electron redox potentials with those of model compound 1 [3-methyl-4-(3‘-methylindol-2‘-yl)indole-6,7-dione] previously reported (ref 5). Reactivity of each quinone in the transamination process [iminoquinone formation (k1), rearrangement to product−imine (k2), and aminophenol formation (k3)] has been investigated kinetically, revealing that the substituent and structural effects on the amine-oxidation reaction are not so significant....

Synthesis and biological activity of a variety of 3- and 6-substituted 1H-pyrrolo[2,3-b]pyridine (7-azaindole) derivatives are described. Many of the synthesized 7-azaindoles exhibited considerable fungicidal activity toward Pyricularia oryzae, a fungus which causes rice blast, in vivo. When quantum parameters of the tested 7-azaindoles were evaluated by semiempirical molecular orbital calculations, a relationship was observed between the activity and the calculated ionization potentials of the 7-azaindole derivatives. Keywords: 1H-Pyrrolo[2,3-b]pyridine; fungicidal activity; ionization potential; rice blast

An efficient system for the catalytic epoxidation reaction of olefins with molecular oxygen was achieved by the utilization of FeCl 2 and the N -heterocyclic podand ligand, N,N′ -bis{2-(4-imidazolyl)ethyl}-2,6-pyridinedicarboxamide (BIPA), without the need for a co-reductant. The pyridyl-substituted N -heterocyclic podand ligand, N,N′ -bis{2-(2-pyridyl)ethyl}-2,6-pyridinedicarboxamide (2-BPEPA) was useful in the Co(OAc) 2 -catalyzed selective oxygenation of phenols to the corresponding p - or o -quinones with molecular oxygen. Efficiency of the oxygenation catalysts largely depends on the coordination interaction with the heterocyclic moieties of the podand ligands.

The reactions of a TTQ model compound [1, 3-methyl-4-(3'-methylindol-2'-yl)indole-6,7-dione] with several amines have been investigated in organic media to obtain mechanistic information on the action of quinoprotein methylamine and aromatic amine dehydrogenases. It has been found that compound 1 acts as an efficient catalyst for the autorecycling oxidation of benzylamine by molecular oxygen in CH(3)OH. In order to evaluate the oxidation mechanism of amines by 1, the product analyses and kinetic studies have been carried out under anaerobic conditions. In the first stage of the reaction of 1 with amines, 1 is converted into an iminoquinone-type adduct (so-called substrateimine), which was isolated and characterized by using cyclopropylamine as a substrate. The observed NOE of the isolated product indicates clearly that the addition position of the amine is C-6 of the quinone. The molecular orbital calculations suggest that the thermodynamic stability of the carbinolamine intermediate is a major factor to determine such regioselectivity; the C-6 carbinolamine is more stable than the C-7 counterpart by 2.9 kcal/mol. The reactivity of several primary amines and the electronic effect of the p-substituents of benzylamine derivatives in the iminoquinone formation suggest that the addition step of the amine to the quinone is rate-determining. When amines having an acidic alpha-proton such as benzylamine derivatives are employed as substrates, formation of the iminoquinone adduct was followed by rearrangement to the productimine. The kinetic analysis has revealed that this rearrangement consists of noncatalyzed and general base-catalyzed processes. Large kinetic isotope effects of 7.8 and 9.2 were observed for both the noncatalyzed and general base-catalyzed processes, respectively, since these steps involve a proton abstraction from the alpha-position of the substrate. In the reaction with benzhydrylamine, the product imine was isolated quantitatively and well characterized by several spectroscopic data. In the case of benzylamine, the product imine is further converted into the aminophenol derivative by the imine exchange reaction with excess benzylamine. These results indicate clearly that the amine oxidation by compound 1 proceeds via a transamination mechanism as suggested for the enzymatic oxidation of amines by TTQ cofactor.

Polyfunctionalized heterocycles have been important key compounds in the fields of functional and biologically active substances. From this point of view, we have developed novel synthetic methods for polyfunctionalized heterocycles according to the following approaches, 1) polar cycloadditions of three-membered heterocycles and azadienes, 2) functionalization of pyridine nucleus leading to condensed pyridine derivatives, 3) molecular design of novel electron transfer catalysts based on chemical simulation of coenzyme PQQ and TTQ, 4) application of heteroatom compounds as heterocyclic building blocks.

An efficient catalytic system for oxygenation of phenols to the p - or o -quinones with molecular oxygen was achieved by utilization of a complex catalyst consisting of Co(OAc) 2 and the multidentate N -heterocyclic podand ligand, N,N ′-bis{2-(2-pyridyl)ethyl}-2,6-pyridinedicarboxamide.

The crystal structure of azurin from a denitrifying bacterium, Achromobacter xylosoxidans NCIB11015, has been refined at 2.5 A resolution using diffraction data obtained by means of synchrotron radiation at KEK. Crystals suitable for X-ray experiment were obtained by the macro-seeding method and an intensity data were obtained on imaging plates mounted on a Weissenberg camera (Rmerge = 0.09). The initial model was obtained by the molecular replacement method using the structure of azurin from Alcaligenes denitrificans NCTC8582 as a starting model. The structure was refined by molecular dynamics optimization and the restrained least-squares method to a crystallographic R-value of 0.205. However, the current model gave an electron-density of the side-chain regions of several residues close to the N-terminus quite different from those expected from the amino acid sequences reported. Very recently, two kinds of azurins (Az-I and Az-II) were isolated from this bacterium by a slightly modified purification method and have been characterized and found to have different CD spectra. On analysis of amino acid sequences around the N-terminus, the second azurin (Az-II) was proved to be a new type of azurin in this bacterium. It was consequently revealed that the current model corresponds to a new type of azurin because of the complete agreement between the electron-density and the amino acid sequence of the newly determined 20 residues from the N-terminus. Determination of the whole amino acid sequence of this azurin and further refinement are in progress.

Benzylic silanes bearing an electron-donating group at the ortho - or para -position underwent the oxovanadium(V)-induced one-electron oxidative desilylation due to low ionization potential, which was applied to the intermolecular regioselective coupling with allylic silanes or silyl enol ether.

The chemoselective cross-coupling of silyl enol ethers and allylic silanes to γ,δ-unsaturated ketones is achieved by the oxovanadium (V)-induced oxidative desilylation of the more readily oxidizable organosilicon compounds.

Coexistence of 4-ethoxycarbonyl-3-methyl-2-cyclohexen-1-one facilitated the epoxidation reaction of styrenes with molecular oxygen catalyzed by FeCl2 and the multidentate N-heterocyclic podand ligand, N,N′-bis{2-(4-imidazolyl)ethyl}-2,6-pyridinedicarboxamide.

A b s t r a c t : The model compound of TTQ (tryptophan tryptophylquinone), the active site cofactor of bacterial methylamine dehydrogenases, was synthesized for the first time. 1H NMR analysis and theoretical calculations on the model compound (1) indicate that its molecular geometry is close to that of TTQ in the enzyme active site. The redox potential and spectral characteristics (W-vis and resonance Raman) of 1 were also very similar to those of the native enzymes. Model compound 1 catalyzes the oxidation of benzylamine in CH30H, indicating that it possesses the same chemical functions as methylamine dehydrogenases. Product analysis on the reactions of 1 with several amines indicate that the amine oxidation proceeds via a transamination mechanism. In order t o study structure-reactivity relationships of TTQ, 4-substituted-6,7-indolequinones were also synthesized and their physicochemical properties and catalytic activity in the amine oxidation were compared to those of model compound 1.

VO (OR) Cl2 is revealed to be a Lewis acid with one-electron oxidation capability. The regioselective ringopening oxygenation of cyclic ketones is catalyzed by VO (OEt) Cl2 in ethanol under oxygen to give the diesters or keto esters. The presence of α, β carbon-carbon double bond in the ketones alters the reaction course. 2-Cyclohexen-l-ones undergo dehydrogenative aromatization to give aryl ethers. An oxovanadium compound obtained from VO (OEt) Cl2 and AgOTf or Me3SiOTf works more efficiently. In the cases of 2-cyclopenten-1- ones, 1-acetyl-1-cyclohexene, and β-ionone, allylic oxidation is achieved to introduce an oxo or alkoxyl group at the γ-position. 2-Phenylglycine derivatives are transformed to ethyl benzoate and ethyl phenylglyoxylate by the VO (OEt) Cl2-induced' oxidative deamination and/or decarboxylation. The ring-opening addition of cyclobutanone to olefins bearing an electron-withdrawing group leads to the corresponding E-chloro ester via oxidation of a cyclobutoxide intermediate. Treatment of a mixture of diketene and styrenes with VO (OR) Cl2 gives 3-alkoxycarbony1-2-methyl-5-phenyl-4, 5-dihydrofurans.Oxidative desilylation is selectively realized by one-electron oxidation of organosilicon compounds with VO (OEt) Cl2. Silyl enol ethers undergo the oxidative cross coupling to afford unsymmetrical 1, 4-diketones. Allylic silanes also regioselectively dimerize to 1, 5-hexadienes. Oxidative desilylation of silyl enol ethers and allylic silanes selectively gives γ, δ-unsaturated ketones depending on their redox potentials.The highly stereoselective monodebromination of gem-dibromocyclopropanes is induced or catalyzed by a low valent vanadium species generated from vanadium (III) chloride or CpV (CO) 4 and zinc in dimethoxyethane in a combination with diethyl phosphonate or triethyl phosphite.

[1801-77-0] C2H5Cl2O2V (MW 182.91) InChI = 1/C2H5O.2ClH.O.V/c1-2-3;;;;/h2H2,1H3;2*1H;;/q-1;;;;+3/p-2/fC2H5O.2Cl.O.V/h;2*1h;;/qm;2*-1;;m/rC2H5Cl2O2V/c1-2-6-7(3,4)5/h2H2,1H3 InChIKey = DBFQWXKLCGFERX-PVPCXMFZCN (Lewis acid capable of one-electron oxidation; effects oxidative cleavage and oxidative coupling reactions) Physical Data: bp 32–34 °C/1 mmHg; yellow liquid;1 1.47 g cm−3. Solubility: sol most organic solvents such as alcohol, dichloromethane, hexane. Preparative Method: VO(OEt)Cl2 is prepared by addition of ethanol to Vanadyl Trichloride.2 Handling, Storage, and Precautions: moisture sensitive; should be handled under dry inert atmosphere and refrigerated in the dark to prevent decomposition (orange fumes). Avoid breathing the vapor; skin irritant and corrosive. Use in a fume hood.

Physicochemical properties of 2-methylthio-4-methylphenol (1) were examined in order to obtain information about the nature of the newly found cofactor of galactose oxidase. Electrochemical studies and theoretical calculations indicated that the methylthio group works as an electron-withdrawing substituent to stabilize the radical species (one-electron oxidation state) of 1. The absorption spectrum obtained by the pulse radiolysis of 1 was very close to that of the oxidized apoenzyme.

Methanol addition to the trimethyl ester of cofactor PQQ (PQQTME) was investigated in detail to obtain information on the action of quinoprotein methanol dehydrogenase. The hemiacetal-type adduct was easily isolated from a methanol solution of PQQTME. The crystal structure of the adduct was determined by X-ray diffraction for the first time, showing that methanol addition occurred at the S-position (C-S) of the quinone as in the case of the acetone adduct formation. On the other hand, treatment of PQQTME in methanol under acidic conditions gave the dimethyl acetal derivative as a major product for which the addition position of methanol was determined to be C-4 by X-ray crystallographic analysis

Cinnamyltrimethylsilane underwent desilylation via one-electron oxidation with VO(OEt)Cl 2 , which was applied to the cross-coupling with the less oxidizable allylic silanes to give the corresponding 1,5-hexadienes. Chlorination or aromatization based on desilylation was observed on treatment of benzyltrimethylsilane or 3- ethoxycarbonyl-2-methyl-5-trimethylsilyl-5-phenyl-4,5-dihydrofuran with VO(OEt)Cl 2 -Me 3 SiOTf, respectively.

The contribution of the polarized resonance structures to 7-methyl-7H-pyrrolo [2,3,-b] pyridine and 4-methyl-4H-pyrrolo [3,2-b] pyridine, which have recently attracted much attention in physico-chemical studies, was considered based on multinuclear ( 1 H, 13 C and 15 N) NMR spectroscopy and MO calculation. Comparison of the chemical shifts of the compounds with those of other relevant compounds and the effects of concentration and solvents observed by multinuclear NMR suggested that the contribution of the non-polarized structures to both compounds predominates over that of the polarized structures. This result was also supported by ab initio MO calculations using the 6-31G basis set

An efficient system for the catalytic epoxidation reaction of olefins with molecular oxygen was achieved by utilization of FeCl2 or Co(OAc)2 and the N-heterocyclic podand ligand, N,N′-bis{2-(4-imidazolyl)ethyl}-2, 6-pyridine-dicarboxamide (BIPA), without the need for a coreductant. The multidentate coordination of BIPA is considered to serve an important role in the oxygenation.

Coenzyme PQQ is demonstrated to catalyse the oxidative Cα–Cβ fission (dealdolation) of β-hydroxy amino acids under very mild conditions.

VO(OEt)Cl 2 oxidized 2-phenylglycine derivatives via oxidative deamination and/or decarboxylation giving ethyl benzoate and ethyl phenylglyoxylate.

2-Phenylethnylpyridine reacted with dimethyl acetylenedicarboxylate (DMAD) in the presence of a proton source such as an alcohol to give Indolizines having methoxycarbonyl groups at the 2- or 2,3-positions in high yields.

Diketene undergoes a VO(OR)Cl2-induced cyclization with styrenes via ring opening to give 3-alkoxycarbonyl-2-methyl-5-phenyl-4,5-dihydrofurans. Desilylative aromatization to the furans is observed in the reaction with α-triemthylsilylstyrene.

3-Cyano-2-(phenylethynyl)pyridine (1) was cyclized intramolecularly under acidic conditions to give 1,6-naphthyridin-5(6H) one (2) and 5H-pyrano[4,3-b]pyridin-5-one (4). Pyranopyridine 4 was readily transformed to 2 or naphthyridinone 9 having an alkyl substituent at 6-position

Molybdenum pentachloride induced the ring-opening reactions of cyclopropyl phenyl ketone or propyl 2-(trimethylsilylmethyl)cyclopropanecarboxylate to give 1-phenyl-1,2,4-trichloro-1-butene or cis-2-chloro-4-pentanolide, respectively.

The MnTPPCl-catalyzed epoxidation of olefins with hydrogen peroxide is efficiently enhanced by mediation of orthequinones.

An oxovanadium compound obtained from VO(OEt)Cl2 and AgOTf or MesSiOTf efficiently induced dehydrogenative aromatization of α,β-unsaturated cyclohexenones to give aryl ethyl ethers in good yields.

Hitherto unknown or rarely reported sulfur-containing bicyclic β-lactams, 6-and 7-thianonanams, were synthesized by addition of sulfur dichloride to N-allyl-β-styryl-β-lactam

An oxo group is introduced at the allylic position of 3-methyl-2-cyclopenten-1-one and β-ionone on treatment with VO(OR)Cl 2 in ROH. VO(OR)Cl 2 induces γ-alkoxylation in the case of 2-cyclopenten-1-one. Reaction of 1-acetyl-1-cyclohexene with VO(OEt)Cl 2 results in γ-alkoxylation and/or aromatization to give 1-acetyl-3-ethoxy-1-cyclohexene and the corresponding aromatic.

The title compound (5) was synthesized by silica gel assisted cyclization of 2-phenylethynylpyridine-3-carboxylic acid (3). It was also synthesized from 3-cyano-2-phenylethynylpyridine (6) in good yield by basic cyclization processes

The reactions of coenzyme PQQ (pyrroloquinolinequinone) and several amino acids have been investigated in vitro. PQQ catalyses the oxidative decarboxylation of α-amino acids to afford the corresponding aldehydes under aerobic conditions. During the catalytic cycles, PQQ is gradually converted into oxazolopyrroloquinoline (OPQ) derivatives to be deactivated. Product analyses indicate that the reaction proceeds via an ionic mechanism that involves a carbinolamine-type adduct as a key intermediate. From this intermediate, direct decarboxylation (major path) and dehydration followed by decarboxylation and hydrolysis or by intramolecular cyclization (minor paths) competitively occur to give the quinol, the aminophenol and the OPQ derivative, respectively. In the reactions with β-hydroxy amino acids, tyrosine and tryptophan, oxidative dealdolation (Cα–Cβ fission) proceeds effectively. The similar ionic mechanism that involves the carbinolamine-type intermediate is suggested by the product analyses under both aerobic and anaerobic conditions.

An efficient catalytic system for the palladium(II)-induced regioselective ringopening oxidation reaction of α,β,-epoxysilane was achieved by use of trimethyl ester of coenzyme PQQ under molecular oxygen. The redox cycle of the ester was performed with two different oxidation states of vanadium compounds, VCl2 and VO(OEt)3.

Selective functionalization of 1H-pyrrolo[2,3-b]pyridine (7-azaindole) at the 6-position was achieved by Reissert-Henze type reaction. Thus, halogeno (Cl, Br, I), cyano and thiocynato groups were directly introduced to the pyridine ring of 7-azaindole

An efficient system for the catalytic epoxidation reaction of olefins with molecular oxygen was achieved by utilization of FeCl2 or Co(OAc)2 and the N-heterocyclic podand ligand, N,N′-bis{2-(4-imidazolyl)ethyl}-2, 6-pyridine-dicarboxamide (BIPA), without the need for a coreductant. The multidentate coordination of BIPA is considered to serve an important role in the oxygenation.

Silyl enol ethers underwent the VO(OR)Cl2-induced homo- or cross-coupling giving 1,4-diketones selectively via one-electron oxidative desilylation.

Functionalization of 1H-pyrrolo[2,3-b]pyridine (7-azaindole) was studied to provide new compounds directing toward agrochemicals and/or functional materials. Amino groups such as NH2, NH(CH2)2NH2, and NH(CH2)2NH(CH2)2NH2 were introduced onto 6-position of 7-azaindole to form multidentate agents. 6-Amino and 6-iodo derivatives were easily converted to podant-type compounds, N,N′-bis(1H-pyrrolo[2,3-b]pyridin-6-yl)-1,3-benzenedicarboxamide and bis(1H-pyrrolo[2,3-b]pyridin-6-yl)acetylene, respectively. Polyacetylene having 1H-pyrrolo[2,3-b]pyridyl group as a pendant was obtained by polymerization of 6-ethynyl-7-azaindole synthesized by ethynylation of 6-bromo derivative. As functionalization at 3-position of 7-azaindole, syntheses of 3,3′-selenobis[1H-pyrrolo[2,3-b]pyridine] and the corresponding 3,3′-thio compound, as well as 3-carboxyethenyl- and 3-vinyl-7-azaindoles were performed. Some of these products exhibited high fungicidal activity.

VO (OR) Cl2 is revealed to be a Lewis acid with one-electron oxidation capability. The regioselective ringopening oxygenation of cyclic ketones is catalyzed by VO (OEt) Cl2 in ethanol under oxygen to give the diesters or keto esters. The presence of α, β carbon-carbon double bond in the ketones alters the reaction course. 2-Cyclohexen-l-ones undergo dehydrogenative aromatization to give aryl ethers. An oxovanadium compound obtained from VO (OEt) Cl2 and AgOTf or Me3SiOTf works more efficiently. In the cases of 2-cyclopenten-1- ones, 1-acetyl-1-cyclohexene, and β-ionone, allylic oxidation is achieved to introduce an oxo or alkoxyl group at the γ-position. 2-Phenylglycine derivatives are transformed to ethyl benzoate and ethyl phenylglyoxylate by the VO (OEt) Cl2-induced' oxidative deamination and/or decarboxylation. The ring-opening addition of cyclobutanone to olefins bearing an electron-withdrawing group leads to the corresponding E-chloro ester via oxidation of a cyclobutoxide intermediate. Treatment of a mixture of diketene and styrenes with VO (OR) Cl2 gives 3-alkoxycarbony1-2-methyl-5-phenyl-4, 5-dihydrofurans.Oxidative desilylation is selectively realized by one-electron oxidation of organosilicon compounds with VO (OEt) Cl2. Silyl enol ethers undergo the oxidative cross coupling to afford unsymmetrical 1, 4-diketones. Allylic silanes also regioselectively dimerize to 1, 5-hexadienes. Oxidative desilylation of silyl enol ethers and allylic silanes selectively gives γ, δ-unsaturated ketones depending on their redox potentials.The highly stereoselective monodebromination of gem-dibromocyclopropanes is induced or catalyzed by a low valent vanadium species generated from vanadium (III) chloride or CpV (CO) 4 and zinc in dimethoxyethane in a combination with diethyl phosphonate or triethyl phosphite.

Reductive deconjugation of α-bromo α,β-unsaturated esters was performed by DP(O)(OEt)2 or P(OEt)3–H2O in the presence of triethylamine from mechanistic viewpoint and was applied to the synthesis of a precursor of (±)-patulolide A.