A novel lumazine synthase inhibitor derived from oxidation of 1,3,6,8-tetrahydroxy-2,7-naphthyridine to a tetraazaperylenehexaone derivative

Air oxidation of 1,3,6,8-tetrahydroxy-2,7-naphthyridine afforded 2,5,8,11-tetraaza-5,11-dihydro-4,10-dihydroxyperylene-1,3,6,7,9,12-hexaone. X-ray crystallography of the product revealed that it exists in the meso form in the solid state. The mechanism of product formation most likely involves oxidative phenolic coupling and oxidation. The product proved to be a competitive inhibitor of Schizosaccharomyces pombe lumazine synthase with a Ki of 66+/-13 microM in Tris buffer and 22+/-4 microM in phosphate buffer. This is significantly more potent than the reactant (Ki 350+/-76 microM, competitive inhibition), which had previously been identified as a lumazine synthase inhibitor by high-throughput screening. Ab initio calculations indicate that the meso form is slightly less stable than the enantiomeric form, and that the two forms interconvert rapidly at room temperature.     

Preparation of hexafluoro-1,8- and -2,7-naphthyridine

Hexachloro-1,8- and -2,7-naphthyridine have been prepared from 2,7-dichloro-1,8-naphthyridine and 1,3,6,8-tetrachloro-2,7- naphthyridine respectively. From these products and their starting materials a series of partially and totally fluorine substituted compounds have been derived.     

A luminescent rhenium(I) complex of 2,7-dimethyl-1,8-naphthyridine: synthesis,spectroscopy and X-ray crystal structure

2,7-Dimethyl-1,8-naphthyridine (L¹) reacts with pentacarbonylchlororhenium in toluene or chloroform to give the target complex fac-{ReCl(CO)₃(L¹)}. X-ray crystallographic data were obtained for fac-{ReCl(CO)₃(L¹)}. The structural and ¹H NMR data suggest that the ligand coordinates to the rhenium in a bidentate fashion in both solid and solution states. The complex was also found to be luminescent in both solution and solid states. The fluxionality of the ligand in solution causes ligand-centred emission to be observed in solution, whereas only ³MLCT emission was observed in the solid state. Although the complex was air-stable, the lability of L¹ was studied in ¹H NMR experiments where CD₃OD induced complete ligand dissociation over the course of 24 h, and also in reaction of fac-{ReCl(CO)₃(L¹)} with one equivalent of 2,2′-bipyridine in chloroform which resulted in quantitative ligand exchange. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Synthesis of bis-2,7-substituted 1,2,3,6,7,8-hexahydroisoindolo[5,6-f]isoindole-1,3,6,8-tetraones

A series of bis-2,7-substituted 1,2,3,6,7,8-hexahydroisoindolo[5,6-f]isoindole-1,3,6,8-tetraones (naphthalene diimides) has been synthesized. The key intermediate required for synthesis of the naphthalene diimides, 2,3,6,7-naphthalnetetracarboxylic dianhydride ( 2 ) was prepared starting from allene and maleic anhydride. The bis-anhydride 2 was converted to the naphthalene diimides using conventional methodology by the reaction with amines in organic solvents.     

Molecular structures of (5454) macrotetracyclic chelates of 3d M(II) ions with 4,5,9,10-tetramethyl-1,3,6,8-tetraaza-5,8-cyclodecadiene-2,7-diimine according to DFT quantum-chemical calculations

The molecular structures of (5454)macrotetracyclic M(II) complexes with the tetradentate ligand with the (NNNN)-coordination of donor sites formed by the template reactions in the ternary systems M(II)-aminomethanamidine (H₂N-C(=NH)-NH₂)-3-hydroxy-2-butanone H₃C-C(=O)-C(OH)-CH₃), where M = Mn, Fe, Co, Ni, Cu, and Zn, have been calculated by the OPBE/TZVP density functional theory (DFT) method. The bond lengths and bond and torsion angles in the complexes, as well as the standard enthalpies, entropies, and Gibbs energies of formation of these compounds, are reported.     

2,7-Bis(1H-pyrrol-2-yl)ethynyl-1,8-naphthyridine: an ultrasensitive fluorescent probe for glucopyranoside

[structure: see text] A push-pull conjugated molecule, 2,7-bis(1H-pyrrol-2-yl)ethynyl-1,8-naphthyridine (BPN), has been designed to bind selectively with octyl glucopyranoside (OGU). The BPN/OGU quadruple hydrogen-bonding complex adopts a rigid BPN conformation in which the proton donor (d) and acceptor (a) relays (daad) are resonantly conjugated through the ethynyl bridge, inducing pi-electron delocalization, i.e., a charge transfer effect. The excellent photophysical properties make BPN a highly sensitive probe for monitoring glucopyranoside to a detection limit of approximately 100 pM.     

Synthesis of new heterocyclic systems fused at pyrazolo[3,4-c]-2,7-naphthyridine core

Efficient syntheses of new heterocyclic systems comprising pyrimido[1',2':1,5]pyrazolo[3,4-c]-2,7-naphthyridine, pyrazolo[3,4-c][1,2,4]triazolo[3,4-a]-2,7-naphthyridine and pyrazolo[3,4-c]tetrazolo[5,1-a]-2,7-naphthyridine cores were performed in two simple steps. In the first step, pyrazole ring was fused at the 2-chloro-3-cyanopyridine moiety by treatment with hydrazine. In the second step, pyrimidine part was fused at the thus formed 3-aminopyrazole moiety by heterocyclization with acetylacetone.     

6H-anthra[1,9,8-c,d,e,f]-2,7-naphthyridine derivatives

5,7-Dinitro derivatives are formed in the nitration of 2H,10H-anthra[1,9,8-c,d,e,f]-2,7-naphthyridine-1,6,11-trione and its N,N'-dimethyl derivatives. 5,7-Dichloro- and 5,7-dibromoanthranaphthyridine-1,6,11-triones were obtained by reaction of 1,8-diamino-4,5-dihaloanthraquinones with diethyl malonate. Disubstituted anthranaphthyridine triones react with amines to give the corresponding 5,7-diaryl(alkyl)aminoanthranaphthyridine 1,6,11-triones.See [1] for communication I.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1645–1648, December, 1976.     

6H-anthra[1,9,8-c,d,e,f]-2,7-naphthyridine derivatives

Derivatives of a new heterocyclic system- 6H-anthra[1,9,8-c,d,e,f]-2,7-naphthyridine-were obtained by condensation of 1,8-diaminoanthraquinone with malonic ester, acetoacetic ester, and benzoylacetic ester.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 679–681, May, 1974.     

Synthesis of furo[2,3-c]-2,7-naphthyridine derivatives via domino heterocyclization reaction

2-Amino-4-cyanomethyl-6-dialkylamino-3,5-pyridinedicarbonitriles were found to react with substituted oxiranes yielding 5,6-diamino-8-dialkylamino-1,2-dihydrofuro[2,3-c]-2,7-naphthyridine-9-carbonitriles. The oxirane ring was shown to be opened selectively from the unsubstituted side and further cyclization occurred with participation of 3-CN, but not 5-CN of the starting pyridines. The furonaphthyridines obtained were converted into 2-dialkylamino-5-methyl-9,10-dihydro-4H-furo[2,3-c]pyrimido[4,5,6-ij]-2,7-naphthyridine-1-carbonitriles and 2-dialkylamino-5,6,9,10-tetrahydro-4H-spiro{furo[2,3-c]pyrimido[4,5,6-ij]-2,7-naphthyridine-5,1′-cyclohexane}-1-carbonitriles by treatment with acetic anhydride and cyclohexanone, respectively. The structure of prepared compounds was confirmed unambiguously by X-ray crystallographic study.     

1,3,6,8-Tetraazapyrenes: synthesis, solid-state structures, and properties as redox-active materials

A series of new tetraazapyrene (TAPy) derivatives has been synthesized by reducing 1,4,5,8-tetranitronaphthalene to its corresponding tin salt (I) and reacting it with perfluorinated alkyl or aryl anhydrides. The resulting 2,7-disubstituted TAPy molecules and the known parent compound 1,3,6,8-tetraazapyrene (II) have been further derivatized by core chlorination and bromination. The brominated compounds served as starting materials for Suzuki cross-coupling reactions with electron-poor arylboronic acids. Single-crystal X-ray analyses established polymorphism for some TAPy compounds. The ground-state geometries of all new TAPy derivatives were modeled with DFT methods [B3PW91/6-31 g(d,p) and B3PW91/6-311+g(d,p)], especially focusing on the energies of the lowest unoccupied molecular orbital (LUMO) and the electron affinities (EA) of the molecules. The results of the calculations were confirmed experimentally by cyclic voltammetry to evaluate the substitution effects at the 2 and 7 position and the core positions, respectively, and gave LUMO energy levels that range from -3.57 to -4.14 eV. Fabrication of organic field-effect transistors (OFETs) with several of these tetraazapyrenes established their potential as organic n-type semiconductors.     

Diisophorone and related compounds—IV: 2,7-Epoxydiisophoranes: synthesis and reactions of 3,4-diketo-2,7-epoxydiisophoran-1-OL

Selenium dioxide oxidises 2,7 - epoxydiisophoran - 1 - ol - 3 - one to the corresponding yellow 3,4-diketone. This is reduced to diisophor - 2(7) - en - 1 - ol - 3 - one (“diisophorone”) by Zn in acetic acid or on catalytic hydrogenation, or to 2,7 - epoxydiisophorane - 1,3,4 - triol by LAH or NaBH₄. Alkaline H₂O₂ cleaves ring A of the 3,4-diketone, providing a degradation of the diisophorane- to the bicyclo[3.3.1]nonane-system. The resulting 3 - (2' - carboxy - 2',2' - dimethyl)ethyl -2, 3 - epoxy -1 - hydroxy - 5,7,7 - trimethylbicyclo(3.3.1]nonane - 2- carboxylic acid is convertible into its dimethyl ester by the action of diazomethane.     

Preparative synthesis of 2,2,6,6-tetramethyl-4-oxopiperidin-1-oxyl

Summary When triacetonamine was slowly oxidized with an aqueous solution of hydrogen peroxide in the presence of sodium tungstate at room temperature, 2,2,6,6-tetramethyl-4-oxopiperidin-1-oxyl was obtained in good yield.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 12 p. 2218, December, 1964     

1,3,6,8-Tetraethynylpyrene and 1,3,6,8-tetrakis (trimethylsilylethynyl) pyrene: Photophysical properties in homogeneous media

The photophysical properties of two new tetra substituted derivatives of pyrene: 1,3,6,8-tetraethynylpyrene (TEP) and 1,3,6,8-tetrakis(trimethylsilylethynyl)pyrene (TEP-TMS) have been studied. Studies were done with respect to mirror image symmetry in the absorption and emission spectra and permissive or forbidden nature of S₀–S₁ transition, solvent sensitivity of the first and third vibronic bands and fluorescence anisotropy. Both the derivatives exhibited a strongly allowed S₀–S₁ transition, high fluorescence quantum yield, shorter fluorescence lifetime compared to pyrene and invariance of the vibronic band intensity ratio to solvent polarity. The behavior of the two pyrene derivatives validates the hypothesis “solvent polarity mediates vibronic coupling and therefore the emission band intensities, for forbidden S₀–S₁ transitions”. The trimethylsilyl derivative (TEP-TMS) was characterized by a strong fluorescence in solid state. The tetraethynyl derivative (TEP) showed high fluorescence anisotropy comparable to the well-known anisotropy probe DPH in glycerol at 0 °C. The fluorescence intensities of TEP and TEP-TMS did not show any significant change in the temperature ranger 0–40 °C for a low viscous solvent like ethanol and in the range 0–60 °C in glycerol. Unlike pyrene, no excimer emission was observed even up to 10⁻³ M for TEP and TEP-TMS.     

Dinuclear Rh(I) complex with 2,7-bis(diphenylphosphino)-1,8-naphthyridine: Synthesis,structure, and dynamic property

Reaction of [RhCl(cod)]₂ with 2,7-bis(diphenylphosphino)-1,8-naphthyridine (dpnapy) and 2,6-xylyl isocyanide (XylNC) in the presence of NH₄PF₆ afforded the dirhodium(I) complex, [Rh₂(μ-dpnapy)₂(XylNC)₄](PF₆)₂ (5), and similar procedures using [MCl₂(cod)] (M = Pt, Pd) resulted in the formation of [Pt₂(μ-dpnapy)₂(XylNC)₄](PF₆)₄ (6) and [Pd₂Cl₂(μ-dpnapy)₂(XylNC)₂](PF₆)₂ (7). Complexes 5–7 were characterized by elemental analysis, IR, UV–Vis, ¹H and ³¹P{¹H} NMR, and ESI mass spectroscopic techniques, to involve a small and rigid d⁸ {M₂(μ-dpnapy)₂} metallomacrocycle. Complex 5 readily incorporated a silver(I) ion into the macrocycle to afford [Rh₂Ag(μ-dpnapy)₂(XylNC)₄](PF₆)₃ (8) which was characterized by X-ray crystallography. The Ag(I) ion is trapped by two trans N atoms of dpnapy ligands, resulting in an asymmetric Rh–Ag⋯Rh structure, determined as a disordered model in the crystal structure, and however, in a CH₂Cl₂ solution, a dynamic interconversion of the two Ag-trapped sites was observed with low-temperature NMR studies, which was further supported by DFT molecular orbital calculations. When an acetonitrile solution of complex 5 was treated over a droplet of mercury(0), the polymeric compound formulated as {[Rh(μ-dpnapy)(XylNC)₂](PF₆)}_n (9) was isolated as yellow single crystals, which were revealed by X-ray crystallography to consist of C₆ helical rods along c axis with a pitch of 33.5 Å (rise of unit = 5.6 Å) and a diameter of 20.64 Å.     

On the synthesis and animation of 5-chloro-and 5-bromo-1,7-naphthyridine

A new synthesis of 5-chloro- and 5-bromo-1,7-naphthyridine, using 8-amino-1,7-naphthyridine as starting material is described. On amination with potassium amide in liquid ammonia, the 5-bromo compound undergoes a tele-amination into 8-amino- and 2-amino-1,7-naphthyridine and a Chichibabin reaction yielding 8-amino-5-bromo-1,7-naphthyridine. The reaction with the 5-chloro compound occurs at a much lower rate than the 5-bromo compound and only gives 8-amino-5-chloro-1,7-naphthyridine in a small yield. Convincing ¹H-nmr evidence is presented, showing that the 5-bromo- and 5-chloro-1,7-naphthyridine give addition of the amide ion at position 8 and that the 5-chloro compound also gives addition at position 2.