A catalyst-free approach to synthesis of spiroacenaphthylene-pyranopyrazole derivatives in water media.

A simple approach for the synthesis of spiroacenaphthylene-pyranopyrazole derivatives was achieved via the reaction between acenaphthoquinone, pyrazolones, and activated methylene compounds (malononitrile derivatives) in water as a green solvent without using any catalyst in order to avoid the use of transition metal. This method has the advantages of mild reaction condition, short reaction time, easy workup, excellent yields, and avoidance of environmentally hazardous solvents.

An Efficient Synthesis of Acenaphtho[1,2-b]indole Derivatives via Domino Reaction.

A concise and efficient synthesis of acenaphtho[1,2-b]indole derivatives via the domino reactions of enaminones with acenaphthoquinone catalyzed by l-proline has been developed. This protocol has the advantages of good yields, operational convenience and high regioselectivity.

Metal-Catalyzed C-H Bond Activation of 5-Membered Carbocyclic Rings: A Powerful Access to Azulene, Acenaphthylene and Fulvene Derivatives.

Azulene, acenaphthylene and fulvene derivatives exhibit important physical properties useful in materials chemistry as well as valuable biological properties. Since about two decades ago, the metal-catalyzed functionalization of such compounds, via C-H bond activation of their 5-membered carbocyclic ring, proved to be a very convenient method for the synthesis of a wide variety of azulene, acenaphthylene and fulvene derivatives. For such reactions, there is no need to prefunctionalize the 5-membered carbocyclic rings. In this review, the progress in the synthesis of azulene, acenaphthylene and fulvene derivatives via metal-catalyzed C-H bond activation of their 5-membered carbocyclic ring are summarized.

Tridecacyclene: A Cyclic Tetramer of Acenaphthylene.

In this manuscript, we describe the single-step preparation of a cyclic tetramer of acenaphthylene through a Lewis acid-catalyzed aldol cyclization of 1-acenaphthenone. The previously unexplored cyclic tetramer material differs from the better-known cyclic trimer, decacyclene, due to the presence of a central eight-membered ring. This ring not only forces the molecule to distort significantly from planarity, but is also responsible for its unique electronic properties, including a decrease in the reduction potential (by about 0.4 eV) and optical gap (by about 0.73 eV), compared to the more planar decacyclene. The synthesized compound crystallizes into a unique packing structure with significant π-stacking observed between adjacent molecules. Furthermore, due to its saddle-like shape, the cyclic tetramer is able to form shape-complementary interactions between its concave surface and the convex outer surface of buckminsterfullerene to generate cocrystalline supramolecular assemblies.

Synthesis, Fluorescence Spectra, Redox Property and the DNA Binding Studies of 7-phenylacenaphtho[1,2-b]quinoxalin-7-ium chloride: Evidences of the Formation of Neutral Radical Analogue.

Reaction of acenaphthoquinone with N-phenyl-o-phenylenediamine in methanol in presence of HCl yielded 7-phenylacenaphtho[1,2-b]quinoxalin-7-ium chloride, [1][Cl]. [1][Cl] is brightly fluorescencent in dichloromethane (λex = 403 nm and λem = 442, 464, 488 nm) and water (λex = 408 nm and λem = 545 nm). Density functional theory (DFT) and time dependent (TD) DFT calculations on [1](+) at the B3LYP level of the theory elucidated that the origin of the lower energy excitation at around 400 nm is due to π → π(*) transition. [1](+) is redox active and exhibits a reversible cathodic wave at -0.66 V referenced to Fc(+)/Fc couple due to [1](+)/[1](•) redox couple. Electrogenerated neutral radical analogue [1](•) was characterized by electron paramagnetic resonance (EPR), UV-vis spectra and DFT calculations. DNA binding studies using the techniques of UV-vis absorption, fluorescence, circular dichroism (CD) spectra, viscosity, gel electrophoresis, hydrodynamic, isothermal titration calorimetry (ITC) and UV optical melting studies of [1][Cl] revealed that [1](+) is a strong DNA intercalator obeying neighbor exclusion principle. ITC experiment authenticated that the binding of [1](+) to DNA is entropy driven.

Synthesis of novel 16-spiro steroids: spiro-7'-(aryl)tetrahydro-1H-pyrrolo[1,2-c][1,3]thiazolo-trans-androsterone hybrid heterocycles.

The 1,3-dipolar cycloaddition of azomethine ylide derived in situ from the reaction of acenaphthylene-1,2-dione and 1,3-thiazolane-4-carboxylic acid to various exocyclic dipolarophiles synthesized from trans-androsterone and trans-dehydroandrosterone afforded a library of novel spiro[5'.2″]acenaphthylene-1″-one-spiro[16.6']-(7'-aryl)-tetrahydro-1H-pyrrolo [1,2-c][1,3]thiazolo-trans-androsterone/dehydroandrosterone hybrid heterocycles respectively. These reactions proceeded stereo-specifically affording a single isomer of the 16-spiro steroids in excellent yields.

Three-component, one-pot sequential synthesis of functionalized cyclazines: 3H-1,2a1,3-triazaacenaphthylenes.

An efficient tandem route to the synthesis of 3H-1,2a(1),3-triazaacenaphthylene derivatives of the cyclazine family has been developed. Target compounds were obtained in moderate to good yields by a Yb(OTf)(3)/Ag(2)CO(3)-catalyzed, three-component domino reaction. This in turn will set the stage for a wide application of this useful reaction for the synthesis of structurally diverse polyheterocyclic skeletons containing the imidazo[1,2-a]pyridine privileged structure.

CaCl(2) as a bifunctional reusable catalyst: diversity-oriented synthesis of 4H-pyran library under ultrasonic irradiation.

CaCl(2) is applied as an efficient reusable and eco-friendly bifunctional catalyst for the one-pot three-component synthesis of 4H-pyrans under ultrasonic irradiation. A broad range of substrates including the aromatic and heteroaromatic aldehydes, indoline-2,3-dione (isatin) derivatives, acenaphthylene-1,2-dione (acenaphthenequinone) and 2, 2-dihydroxy-2H-indene-1,3-dione (ninhydrin) were condensed with carbonyl compounds possessing a reactive α-methylene group and alkylmalonates. All reactions are completed in short times, and the products are obtained in good to excellent yields. The catalyst could be recycled and reused several times without any loss of efficiency.

Synthesis of functionalized acenaphthenes and a new class of homooxacalixarenes.

The 5,6-dialkoxyethers of acenaphthene have been synthesized for the first time via modified Ullmann reaction conditions. Further modifications of the 5,6-dimethoxyacenaphthene allowed the synthesis of the first acenaphthene analogue of the octahomotetraoxacalixarenes. The X-ray structure of this new macrocycle and its complexation study with C(60) are reported.

Multicomponent approaches to 8-carboxylnaphthyl-functionalized pyrazolo[3,4-b]pyridine derivatives.

A simple and novel protocol for the efficient synthesis of a series of 8-carboxylnaphthyl functionalized pyrazolo[3,4-b]pyridine derivatives was developed through a one-pot, three-component reaction involving acenaphthylene-1,2-dione and 1H-pyrazol-5-amine in acetic acid medium. The reaction represents the first facile conversion of acenaphthenequinone to naphthoic acid via C-C bond cleavage without need for multi-step transformation.

Acenaphtho[1,2-b]pyrrole-based selective fibroblast growth factor receptors 1 (FGFR1) inhibitors: design, synthesis, and biological activity.

A novel series of acenaphtho[1,2-b]pyrrole derivatives as potent and selective inhibitors of fibroblast growth factor receptor 1 (FGFR1) were designed and synthesized. In silico target prediction revealed that tyrosine kinases might be the potential targets of the representative compound 2, which was subsequently validated by enzyme-linked immunosorbent assay (ELISA) for its selective and active FGFR1 inhibition of various tyrosine kinases. The structure-activity relationship (SAR) analysis aided by molecular docking simulation in the ATP-binding site demonstrated that acenaphtho[1,2-b]pyrrole carboxylic acid esters (2-5) are potent inhibitors of FGFR1 with IC(50) values ranging from 19 to 77 nM. Furthermore, these compounds exhibited favorable growth inhibition property against FGFR-expressing cancer cell lines with IC(50) values ranging from micromolar to submicromolar. Western blotting analysis showed that compounds 2, 3, and 2b inhibited activation of FGFR1 and extracellular-signal regulated kinase 1/2 (Erk1/2).

Syntheses, structures and antimicrobial activities of bis(imino)acenaphthene (BIAN) imidazolium salts.

The syntheses of four new bis(imino)acenaphthene (BIAN) imidazolium chlorides are reported, three of which have been structurally characterized. The synthesis of a new, structurally authenticated BIAN ligand is also described. We report the results of the use of these BIAN imidazolium salts as antimicrobials against the pathogens S. aureus, B. subtilis, E. coli and P. aeruginosa. The antimicrobial efficacies were particularly high for the N-(2,6-diisopropylphenyl)- and N-(mesityl)-substituted BIAN imidazolium salts (MIC values < 0.6 µg/mL).

Synthesis and biological evaluation of novel acenaphthene derivatives as potential antitumor agents.

Twelve novel acenaphthene derivatives have been synthesized. The structures of all compounds were confirmed by ¹H-NMR, MS and elemental analysis. Their antitumor activities were evaluated in six human solid tumor cell lines, namely non-small cell lung cancer (H460), human colon adenocarcinoma (SW480), human breast cancer cell (MDA-MB-468 and SKRB-3), human melanoma cell (A375) and human pancreatic cancer (BxPC-3). Among them, compound 3c shows the best antitumor activity against SKRB-3 cell line, as high as the positive control adriamycin.

Ultrasound-assisted synthesis of 2,2'-(2-oxoindoline-3,3-diyl)bis(1H-indene-1,3(2H)-dione) derivatives.

A simple and efficient procedure for the synthesis of 2,2'-(2-oxoindoline-3,3-diyl)bis(1H-indene-1,3(2H)-dione) derivatives, 2,2'-(2-oxo-1,2-dihydroacenaphthylene-1,1-diyl)bis(1H-indene-1,3(2H)-dione) and 2,2'-(1,3-dioxo-2,3-dihydro-1H-indene-2,2-diyl)bis(1H-indene-1,3(2H)-dione) by the reaction of 1,3-indandione and isatins or acenaphthylene-1,2-dione or ninhydrine in ethanol under ultrasonic irradiation in the presence of p-TSA is reported. The advantages of this method are the use of an inexpensive and readily available catalyst, easy work-up, good yields, and the use of ethanol as a solvent that is considered to be relatively environmentally benign.

Novel acenaphtho[1,2-b]pyrrole-carboxylic acid family: synthesis, cytotoxicity, DNA-binding and cell cycle evaluation.

A family of 8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carboxylic acid derivatives were synthesized as a result of our efforts to modify a series of acenaphthopyrrole aromatic-heterocycle compounds that proved to be potent anticancer drugs. Among the derivatives, 3d (3-(dimethylamino-propylamino)-8-oxo-8H-acenaphtho-[1,2-b]pyrrole-9-carboxylic acid) and 3g (3-piperidine-8-oxo-8H-acenaphtho-[1,2-b]pyrrole-9-carboxylic acid) showed potential anticancer activity and different action mechanism from our previously reported compounds. UV-vis absorption, circular dichroism and viscosity measurement indicated that effect of both compounds on the advanced DNA conformation was different, although they could bind to DNA in the same way. Cell cycle analysis showed that 3d could induce S-phase arrest followed by apoptosis, while 3g induced apoptosis. The results seem to imply that different action mechanism could contribute to the dissimilitude of biological activities toward 3d and 3g.

A new bis(1-naphthylimino)acenaphthene compound and its Pd(II) and Zn(II) complexes: synthesis, characterization, solid-state structures and density functional theory studies on the syn and anti isomers.

A new rigid bidentate ligand, bis(1-naphthylimino)acenaphthene, L1, and its Zn(II) and Pd(II) complexes [ZnCl 2( L1)], 1, and [PdCl 2( L1)], 2, were synthesized. L1 was prepared by the "template method", reacting 1-naphthyl amine and acenaphthenequinone in the presence of ZnCl 2, giving 1, which was further demetallated. Reaction of 1-naphthyl amine with acenaphthenequinone and PdCl 2 afforded dichloride bis(1-naphthyl)acenaphthenequinonediimine palladium, 2. L1, 1, and 2 were obtained as a mixture of syn and anti isomers. Compound 2 was also obtained by the reaction of PdCl 2 activated by refluxing it in acetonitrile followed by the addition of L1; by this route also a mixture of syn and anti isomers was obtained, but at a different rate. The solid-state structures of L1 and the anti isomer of compound 2 have been determined by single-crystal X-ray diffraction. All compounds have been characterized by elemental analyses; matrix-assisted laser desorption ionization-time-of-flight-mass spectrometry; IR; UV-vis; (1)H, (13)C, and (1)H- (1)H correlation spectroscopy; (1)H- (13)C heteronuclear single quantum coherence; (1)H- (13)C heteronuclear single quantum coherence-total correlation spectroscopy; and (1)H- (1)H nuclear Overhauser effect spectrometry NMR spectroscopies when applied. Density functional theory studies showed that both conformers for [PdCl 2(BIAN)] are isoenergetic, and they can both be obtained experimentally. However, we can predict that the isomerization process is not available in a square-planar complex, but it is possible for the free ligand. The molecular geometry is very similar in both isomers, and only different orientations for naphthyl groups can be expected.

Radical-molecule reactions for aromatic growth: a case study for cyclopentadienyl and acenaphthylene.

Polycyclic aromatic hydrocarbon growth from acenaphthylene and cyclopentadienyl was investigated by using the B3LYP/6-31G(d,p) and BH&HLYP/6-31G(d,p) levels of theory as well as transition state theory. The reaction pathways of cyclopentadienyl bearing hydrocarbons are different from those without these moieties and cannot be adequately accounted for by the existing acetylene addition and aryl-aryl addition mechanisms. The reaction mechanisms identified in this paper lead to the formation of fluoranthene, aceanthrylene, and acephenanthrylene. Rate constants of the radical-molecule addition and subsequent intramolecular addition steps predict that the 1,2 double bond in acenaphthylene is much more reactive than the 3,4 and 4,5 double bonds. Fluoranthene is the most abundant product produced at high temperatures and the yield of acephenanthrylene is bigger than that of aceanthrylene. The computational results are discussed in light of pyrolysis experiments on CPD-indene and CPD-acenaphthylene mixtures conducted by Prof. Mulholland's research group reported in a previous work.

Acenaphtho[1,2-b]pyrrole derivatives as new family of intercalators: various DNA binding geometry and interesting antitumor capacity.

A series of acenaphtho[1,2-b]pyrrole derivatives were synthesized and their intercalation geometries with DNA and antitumor activities were investigated in detail. From combination of SYBR Green-DNA melt curve, fluorescence titration, absorption titration, and circular dichroism (CD) studies, it was identified that to different extent, all the compounds behaved as DNA intercalators and transformed B form DNA to A-like conformation. The different intercalation modes for the compounds were revealed. The compounds containing a methylpiperazine substitution (series I) intercalated in a fashion that the long axis of the molecule paralleled to the base-pair long axis, while the alkylamine- substituted compounds (series II and III) located vertically to the long axis of DNA base pairs. Consequently, the DNA binding affinity of these compounds was obtained with the order of II>III>I, which attributed to the role of the substitution in binding geometry. Further, cell-based studies showed all the compounds exhibited outstanding antitumor activities against two human tumor cell lines with IC(50) ranging from 10(-7) to 10(-6)M. Interestingly, compound (1)a (a compound in series I), whose binding affinity was one of the lowest but altered DNA conformation most significantly, showed much lower IC(50) value than other compounds. Moreover, it could induce tumor cells apoptosis, while the compounds (2)a and (3)a (in series II and III, respectively) could only necrotize tumor cells. Their different mechanism of killing tumor cells might lie in their different DNA binding geometry. It could be concluded that the geometry of intercalator-DNA complex contributed much more to the antitumor property than binding affinity.

Design, synthesis, and antitumor evaluation of novel acenaphtho[1,2-b]pyrrole-carboxylic acid esters with amino chain substitution.

8-Oxo-8H-acenaphtho[1,2-b]pyrrole-9-carboxylic acid esters and derivatives were prepared and evaluated for cytotoxicity against A549 and P388 cell lines. Based on a novel chromophore precursor 8-oxo-8H-acenaphtho[1,2-b]pyrrol-9-carbonitrile 1, the very insoluble 1 was converted to more soluble esters 5 and a series of 3-amino derivatives from 5 were obtained by mild S(N)Ar(H) reaction between 5 and various amines. The biological evaluation indicated that methyl esters 5a are the most cytotoxic with IC(50) values of 0.45 and 0.80 microM (against A549 and P388, respectively) among the parent esters 5a-5f, but 3-amino derivatives 4b and 4c of 5f with bromine showed the highest activity (with IC(50) values of 0.019-0.60 microM) among the 3-amino derivatives.