Studies in terpenoids. Part 42. Synthesis of 3-(2-hydroxyisopropyl)5,8-dimethyl-1,2-naphthoquinone (emmotin-H)

Emmotin-H, a naturally occurring sesquiterpenoid 1,2-naphthoquinone pigment (1) has been synthesised in a four step sequence starting from the known 5,8-dimethyl-4-oxotetralin-2-carboxylic acid (3a). Selenium dioxide oxidation of its methyl ester (3b) gives 3-methoxycarbonyl-5,8-dimethyl-1,2-naphthoquinone (4) which on reductive acetylation affords the corresponding diacetoxynaphthalene ester (5). Its reaction with excess of methylmagnesium iodide is accompanied by aerial oxidation during work-up and furnishes emmotin-H (1).

Involvement of sensory nerves and TRPV1 receptors in the rat airway inflammatory response to two environment pollutants: diesel exhaust particles (DEP) and 1,2-naphthoquinone (1,2-NQ)

The environmental chemical 1,2-naphthoquinone (1,2-NQ) is implicated in the exacerbation of airways diseases induced by exposure to diesel exhaust particles (DEP), which involves a neurogenic-mediated mechanism. Plasma extravasation in trachea, main bronchus and lung was measured as the local (125)I-bovine albumin accumulation. RT-PCR quantification of TRPV1 and tachykinin (NK(1) and NK(2)) receptor gene expression were investigated in main bronchus. Intratracheal injection of DEP (1 and 5 mg/kg) or 1,2-NQ (35 and 100 nmol/kg) caused oedema in trachea and bronchus. 1,2-NQ markedly increased the DEP-induced responses in the rat airways in an additive rather than synergistic manner. This effect that was significantly reduced by L-732,138, an NK(1) receptor antagonist, and in a lesser extent by SR48968, an NK(2) antagonist. Neonatal capsaicin treatment also markedly reduced DEP and 1,2-NQ-induced oedema. Exposure to pollutants increased the TRPV1, NK(1) and NK(2) receptors gene expression in bronchus, an effect was partially suppressed by capsaicin treatment. In conclusion, our results are consistent with the hypothesis that DEP-induced airways oedema is highly influenced by increased ambient levels of 1,2-NQ and takes place by neurogenic mechanisms involving up-regulation of TRPV1 and tachykinin receptors.

Reaction of 2-methyl-1,4-naphthoquinone and its 3-substituted derivatives with active methylene group anions and with diazo compounds

The reaction of 2-chloro-3-methyl-1,4-naphthoquinone (3) with the anion of ethyl cyanoacetate led to a mixture of two epimeric fused-ring cyclopropane compounds, characterised as exo- and endo-1-cyano-1 -ethoxycarbonyl-1a-methyl-1a,7a-dihydro-1H-cyclopropa[b]naphthalene-2,7-dione (8) and (9). Various hydrolysis products of these were prepared and an X-ray crystallographic analysis was carried out on one of them, 1-carbamoyl-1 -carboxy-1a-methyl-1a,7a-dihydro-1H-cyclopropa[b]-naphthalene-2,7-dione (17). The reaction of 2-methyl-1,4-naphthoquinone (1) with ethyl diazoacetate gave a fused pyrazoline derivative, 3-ethoxycarbonyl-4-hydroxy-9a-methyl-1,9a-dihydro-benz[f]indazol-9-one (22), while reaction of 2-methyl-3-nitro-1,4-naphthoquinone (5) with diazomethane led to a fused Δ2-isoxazoline N-oxide, 3a-methyl-3,3a-dihydroisoxazolo[3,4-b]naphthalene-4,9-dione 1-oxide (26).

2-Bromo-1,4-naphthoquinone: a potentially improved substitute of menadione in Apatone therapy

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Green photochemistry: photo-Friedel-Crafts acylations of 1,4-naphthoquinone in room temperature ionic liquids

The photo-Friedel-Crafts acylation of 1,4-naphthoquinone with various aldehydes was investigated in a series of room temperature ionic liquids. High conversions and selectivities were achieved in [C(2)mim](+)-based ionic liquids with the highest isolated yields found in [C(2)mim][NTf2]. The developed procedure allowed for a replacement of hazardous solvents such as benzene and acetonitrile which are commonly used for this transformation.

Reductive electrochemical formation of 6H-dibenzo[b,d]pyran-6-one and 2-benzopyran-1(1H)-one

In the present Letter several carbolactones (oxidative products) are obtained under aprotic cathodic conditions in the preparative scaled electrolysis of 1,2-quinones in a divided electrochemical cell and in the presence of oxygen. When 9,10-phenanthrenequinone is reduced 6H-dibenzo[b,d]pyran-6-one and [1,1′-biphenyl]-2,2′-dicarboxylic acid are obtained as major products. In the reduction of 1,2-naphthoquinone, 2-benzopyran-1(1H)-one, and 2-(2-carboxyethenyl)-benzoic acid were formed as main products. The proposed mechanism to explain the formation of these and other products, that involves an electron-transfer reaction to the oxygen in air, is now discussed.

Tris[4,4,4-trifluoro-1-(2-thienyl)butane-1,3-dionato]aluminium(III)-tris[4,4,4-trifluoro-1-(2-thienyl)butane-1,3-dionato]iron(III) (3/1)

In the title compound, [Al(C8H4F3O2S)3]3[Fe(C8H4F3O2S)3], the metal centre is statistically occupied by AlIII and FeIII cations in a 3:1 ratio. The metal centre is within an octahedral O6 donor set defined by three chelating substituted acetoacetonate anions. The ligands are arranged around the periphery of the molecule with a mer geometry of the S atoms.

An Improved Synthetic Route to the Potent Angiogenesis Inhibitor Benzyl Manα(1→3)-Manα(1→3)-Manα(1→3)-Manα(1→2)-Man Hexadecasulfate

An improved synthetic route to α(1→3)/α(1→2)-linked mannooligosaccharides has been developed and applied to a more efficient preparation of the potent anti-angiogenic sulfated pentasaccharide, benzyl Manα(1→3)-Manα(1→3)-Manα(1→3)-Manα(1→2)-Man hexadecasulfate, using only two monosaccharide building blocks. Of particular note are improvements in the preparation of both building blocks and a simpler, final deprotection strategy. The route also provides common intermediates for the introduction of aglycones other than benzyl, either at the building block stage or after oligosaccharide assembly. The anti-angiogenic activity of the synthesized target compound was confirmed via the rat aortic assay.

Proton-transfer versus nontransfer in compounds of the diazo-dye precursor 4-(phenyldiazenyl) aniline (aniline yellow) with strong organic acids: the 5-sulfosalicylate and the dichroic benzenesulfonate salts, and the 1:2 adduct with 3,5-dinitrobenzoic

The structures of two 1:1 proton-transfer red-black dye compounds formed by reaction of aniline yellow [4-(phenyldiazenyl)aniline] with 5-sulfosalicylic acid and benzenesulfonic acid, and a 1:2 nontransfer adduct compound with 3,5-dinitrobenzoic acid have been determined at either 130 or 200 K. The compounds are 2-(4-aminophenyl)-1-phenylhydrazin-1-ium 3-carboxy-4-hydroxybenzenesulfonate methanol solvate, C12H12N3+.C7H5O6S-.CH3OH (I), 2-(4-aminophenyl)-1-hydrazin-1-ium 4-(phenydiazinyl)anilinium bis(benzenesulfonate), 2C12H12N3+.2C6H5O3S-, (II) and 4-(phenyldiazenyl)aniline-3,5-dinitrobenzoic acid (1/2) C12H11N3.2C~7~H~4~N~2~O~6~, (III). In compound (I) the diaxenyl rather than the aniline group of aniline yellow is protonated and this group subsequently akes part in a primary hydrogen-bonding interaction with a sulfonate O-atom acceptor, producing overall a three-dimensional framework structure. A feature of the hydrogen bonding in (I) is a peripheral edge-on cation-anion association involving aromatic C--H...O hydrogen bonds, giving a conjoint R1/2(6)R1/2(7)R2/1(4)motif. In the dichroic crystals of (II), one of the two aniline yellow species in the asymmetric unit is diazenyl-group protonated while in the other the aniline group is protonated. Both of these groups form hydrogen bonds with sulfonate O-atom acceptors and thee, together with other associations give a one-dimensional chain structure. In compound (III), rather than proton-transfer, there is a preferential formation of a classic R2/2(8) cyclic head-to-head hydrogen-bonded carboxylic acid homodimer between the two 3,5-dinitrobenzoic acid molecules, which in association with the aniline yellow molecule that is disordered across a crystallographic inversion centre, result in an overall two-dimensional ribbon structure. This work has shown the correlation between structure and observed colour in crystalline aniline yellow compounds, illustrated graphically in the dichroic benzenesulfonate compound.

Ethane-1,2-diaminium 4,5-dichlorophthalate

In the structure of the title compound, C2H10N22+·C8H2Cl2O42-, the dications and dianions form hydrogen-bonded ribbon substructures which enclose conjoint cyclic R21(7), R12(7) and R42(8) associations and extend down the c-axis direction. These ribbons inter-associate down b, giving a two-dimensional sheet structure. In the dianions, one of the carboxylate groups is essentially coplanar with the benzene ring, while the other is normal to it [C-C-C-O torsion angles = 177.67 (12) and 81.94 (17)°, respectively].

The structure of the copper(II) complex with 4,5-dichlorophthalic acid: The 1:1 complex 'adduct' salt trans-tetraaqua(2-carboxy-4,5-dichlorobenzoato)(4,5-dichlorobenzene-1,2-dicarboxylic acid)copper(II) 2-carboxy-4,5-dichlorobenzoate

The unusual (1:1) complex ‘adduct’ salt of copper(II) with 4,5-dichlorophthalic acid (H2DCPA), having formula [Cu(H2O)4(C8H3Cl2O4) (C8H4Cl2O4)] . (C8H3Cl2O4) has been synthesized and characterized using single-crystal X-ray diffraction. Crystals are monoclinic, space group P21/c, with Z = 4 in a cell with dimensions a = 20.1376(7), b =12.8408(4) c = 12.1910(4) Å, β = 105.509(4)o. The complex is based on discrete tetragonally distorted octahedral [CuO6] coordination centres with the four water ligands occupying the square planar sites [Cu-O, 1.962(4)-1.987(4) Å] and the monodentate carboxyl-O donors of two DCPA ligand species in the axial sites. The first of these bonds [Cu-O, 2.341(4) Å] is with an oxygen of a HDCPA monoanion, the second with an oxygen of a H2DCPA acid species [Cu-O, 2.418(4) Å]. The un-coordinated ‘adduct’ molecule is a HDCPA counter anion which is strongly hydrogen-bonded to the coordinated H2DCPA ligand [O… O, 2.503(6) Å] while a number of peripheral intra- and intermolecular hydrogen-bonding interactions give a two-dimensional network structure.

Crystallographic characterization of the first reported crystalline form of the potent hallucinogen (R)-2-amino-1-(8-bromobenzo[1,2-b;5,4-b']difuran-4-yl)propane or `bromodragonfly': the 1:1 anhydrous proton-transfer compound with 3,5-dinitrosalicylic acid

The 1:1 proton-transfer compound of the potent substituted amphetamine hallucinogen (R)-1-(8-bromobenzo[1,2-b; 4,5-b']difuran-4-yl)-2-aminopropane (common trivial name 'bromodragonfly') with 3,5-dinitrosalicylic acid, 1-(8-bromobenzo[1,2-b;4,5-b']difuran-4-yl)-2-mmoniopropane 2-carboxy-4,6-dinitrophenolate, C13H13BrNO2+ C7H3N2O7- forms hydrogen-bonded cation-anion chain substructures comprising undulating head-to-tail anion chains formed through C(8) carboxyl O-H...O(nitro) associations and incorporating the aminium groups of the cations. The intra-chain cation-anion hydrogen-bonding associations feature proximal cyclic R33(8) interactions involving both a N+-H...O(phenolate) and the carboxyl O--H...O(nitro)associations. Also present are aromatic pi-pi ring interactions [minimum ring centroid separation, 3.566(2)A; inter-plane dihedral angle, 5.13(1)deg]. A lateral hydrogen-bonding interaction between the third aminium proton and a carboxyl O acceptor link the chain substructures giving a two-dimensional sheet structure. This determination represents the first of any form of this compound and confirms that it has the (R) absolute configuration. The atypical crystal stability is attributed both to the hydrogen-bonded chain substructures provided by the anions, which accommodate the aminium proton-donor groups of the cations and give cross-linking, and to the presence of cation--anion aromatic ring pi-pi interactions.