Phenanthrene Derivatives Research Articles

Effect of n-alkyl chain length on the complexation of phenanthrene and 9-alkyl-phenanthrene with β-cyclodextrin

The characteristics of host–guest complexation between β-cyclodextrin (β-CD) and phenanthrene derivatives (phenanthrene, n-propyl, n-butyl and n-hexyl-phenanthrene) were investigated by fluorescence spectrometry. Linear and non-linear regression methods were used to estimate the formation constants ( K 1). A 1:1 stoichiometric ratio and an effect of n-alkyl chain length on the formation constant were observed for the binary inclusion complex between guest and β-CD. The formation constant dramatically increases with the length of n-alkyl, it starts from the value of 140 l mol −1 for the phenanthrene to reach the value of 580 l mol −1 for hexyl-phenanthrene. The effect of the temperature on the fluorescence intensity of each complex (guest–host) was also studied; and then the thermodynamic parameters were calculated. The main inclusion site seems to be aromatic moiety for short chain molecules, and it moves toward the alkyl chain part, as the chain becomes longer.

Structure-activity analysis of a novel NR2C/NR2D-preferring NMDA receptor antagonist: 1-(phenanthrene-2-carbonyl) piperazine-2,3-dicarboxylic acid.

(2S*,3R*)-1-(biphenyl-4-carbonyl)piperazine-2,3-dicarboxylic acid (PBPD) is a moderate affinity, competitive N-methyl-d-aspartate (NMDA) receptor antagonist with an atypical pattern of selectivity among NMDA receptor 2 subunit (NR2) subunits. We now describe the activity of several derivatives of PBPD tested at both rat brain NMDA receptors using l-[3H]-glutamate binding assays and at recombinant receptors expressed in Xenopus oocytes. Substituting various branched ring structures for the biphenyl group of PBPD reduced NMDA receptor activity. However, substituting linearly arranged ring structures - fluorenone or phenanthrene groups - retained or enhanced activity. Relative to PBPD, the phenanthrene derivative (2S*, 3R*)-1-(phenanthrene-2-carbonyl)piperazine-2,3-dicarboxylic acid (PPDA) displayed a 30- to 78-fold increase in affinity for native NMDA receptors. At recombinant receptors, PPDA displayed a 16-fold (NR2B) to 94-fold (NR2C) increase in affinity over PBPD. Replacement of the biphenyl group of PBPD with a 9-oxofluorene ring system resulted in small changes in receptor affinity and subtype selectivity. 2'-Bromo substitution on the biphenyl group of PBPD reduced antagonist affinity 3- to 5-fold at NR2A-, NR2B- and NR2D-containing receptors, but had little effect on NR2C-containing receptors. In contrast, 4'-fluoro substitution of the biphenyl ring of PBPD selectively increased NR2A affinity. The aromatic rings of PBPD and PPDA increase antagonist affinity and appear to interact with a region of the NMDA receptor displaying subunit heterogeneity. PPDA is the most potent and selective NR2C/NR2D-preferring antagonist yet reported and thus may be useful in defining NR2C/NR2D function and developing related antagonists with improved NMDA receptor subtype selectivity. British Journal of Pharmacology (2004) 141, 508-516. doi:10.1038/sj.bjp.0705644

ASSOCIATIONS BETWEEN CHEMICAL PROPERTIES AND OXIDATIVE DAMAGE DUE TO NITROPHENANTHRENES AND THEIR RELATED COMPOUNDS IN PRIMARY RAT HEPATOCYTES

Nitrated derivatives of phenanthrene, azaphenanthrene, and their N-oxides were synthesized, and their chemical properties, LUMO energy, the first and second reduction potentials, and dihedral angle of nitro groups were investigated. On orientation of 22 nitrophenanthrenes (NPhs), and 19 nitroazaphenanthrenes (NAPhs) containing their N-oxides (NPhOs), NPhs and NAPhs substituted at positions 2, 3, 6, and 7 were almost coplanar to the aromatic ring, while those at positions 1, 5, 8, 9, and 10 were almost perpendicular. On the other hand, primary rat hepatocytes prepared from SD rats efficiently induced 8-oxodeoxyguanine (8-oxo-Gua) of 4-nitroquinoline N-oxide (4-NQO), a mutagen and carcinogen. 8-oxo-Gua formed due to oxidative damage was dose dependent at levels from 1.0 to 5.0 nM of 4-NQO. 8-oxo-Gua formation of NPhs and NAPhs in primary rat hepatocytes was determined, and the results significantly correlated with the first reduction potentials (r = 0.906) and LUMO energy (r = 0.874) of these derivatives. It was concluded that the nitro group of Phs and APhs were metabolized by the NADPH-cytochrome p450 enzyme in primary rat hepatocytes, and a radical anion of NPhs was induced. Finally, the hydroxyl radicals induced promoted hydroxylation at the 8 position of the guanine residue. It was found that these metabolic pathways were closely associated with the first reduction potentials, and the LUMO energy of NPhs and NAPhs, as well as 8-oxo-Gua formation were related to these chemical properties.

Analysis and structure prediction of chlorinated polycyclic aromatic hydrocarbons released from combustion of polyvinylchloride

Chlorinated polycyclic aromatic hydrocarbons (Cl-PAHs) released from combustion of polyvinylchloride (PVC) at different furnace temperatures were investigated. A laboratory-scale tube-type furnace with electric heating was utilized to control combustion conditions. Glass fabric filters and adsorbents were used to collect the combustion emissions. Following Soxhlet extraction, concentration and column chromatography purification, isomers separation, selective detection and identification of Cl-PAHs were performed on GC/MS system on the basis of retention data and mass spectra. Their quantification was accomplished by using external standard calibration technique. About 18 Cl-PAHs were determined, most of which were monochlorinated derivatives of naphthalene, biphenyl, fluorene, phenanthrene, anthracene, fluoranthene and pyrene. Only two dichlorophenanthrenes or anthracenes were identified. The possible positions of chlorine atoms attached to the aromatic rings are predicted by quantitative structure–property relationship. The levels of these compounds were in the range of 0.30–29.08 μg/g PVC. The relationship between the formation of Cl-PAHs and PAHs was discussed.

Chemical Constituents and Pharmacology of the Formosan Aristolochia Species

Aristolochia is an important genus widely cultivated and used in traditional Chinese medicine. The genus has attracted much interest and has been the subject of numerous chemical studies. In the last twelve years, all the Formosan species of Aristolochia have been investigated by our group for their chemical constituents and biological activities. They are sources of a number of physiologically active compounds of different classes, and various types of phenanthrene derivatives, terpenes, alkaloids, flavonoids, lignoids, benzenoids, and steroids have been isolated from Formosan Aristolochia species. The nature of these constituents is compiled in this review together with their bioactivities in an effort to show the rapid development in the phytochemistry and the therapeutic applications of the Aristolochia species.

4,15‐Diamino[2.2]paracyclophane as a Starting Material for Pseudo‐Geminally Substituted [2.2]Paracyclophanes

AbstractDiazotization of the title compound 3, followed by treatment of the formed bis(diazonium ion) with cuprous chloride, yields the pseudo‐geminal dichloride 1. Similarly, 3 is converted into the bis(azide) 5 when sodium azide is used as the trapping nucleophile. Hypochlorite oxidation of 3 furnishes the azo compound 4, the first multi‐bridged cyclophane with a bridge consisting only of heteroatoms. Reduction of 4 with zinc/acetic acid affords the substrate 3 again. Treatment of 4 with bromine/iron powder or iodine monochloride causes deazotization accompanied by halogen introduction in pseudo‐geminal position (i.e., formation of 2 and 6, respectively). Flash vacuum pyrolysis (450 °C, 0.01 Torr) of 4 produces the phenanthrene derivatives 13 and 14, while with tetracyanoethylene (TCNE) the azophane undergoes rapid cycloaddition at room temperature to give the [2+4] cycloadduct 16. The structures of 1, 2, 4−6, and 16 have been determined by X‐ray structural analysis. Molecular packing patterns are determined by weak hydrogen bonds; a common packing pattern for cyclophane derivatives is ascribed to C−H···π interactions. Full bandshape analyses of the bridge proton signals in the 1H NMR spectra of 1, 2, 6, and of the difluoro analogue 17 yielded the vicinal 1H,1H coupling constants. These reflect the 1:1 equilibrium between the two skew conformations of the bridges. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

New Fluorenone and Phenanthrene Derivatives from Dendrobium Chrysanthum

Two new fluorenone derivatives denchrysans A ( 1 ) and B ( 2 ) and one new phenanthrenediglycoside denchryside A ( 3 ) were isolated from the herbs of Dendrobium chrysanthum (Orchidaceae). Their structures were established on the basis of spectral evidence.

A Convergent Method for the Synthesis of Highly Enantiomerically Enriched Cyclic Silanes with Silicon-Centered Chirality

A preparatively straightforward methodology has been developed which allows the assembly of silicon-containing carbocycles as mixtures of diastereomers with silicon as the sole center of stereogenic information. One-step construction of the chiral cyclic silanes is realized by reaction of equimolar amounts of a dibromide and a chirally modified dichlorosilane under Barbier conditions giving access to several monofunctionalized 1-sila-1,2,3,4-tetrahydronaphthalenes and a corresponding phenanthrene derivative. Facile large scale syntheses of 3-(2-bromoaryl)propyl bromides as well as dichlorosilanes have been elaborated. This highly convergent methodology relies on the novel (-)-menthyl-oxy-substituted dichlorosilanes, which have the chiral auxiliary for the subsequent optical resolution installed. These enantiopure dichlorosilanes are useful building blocks for a general and modular one-step approach to silanes with silicon-centered chirality since this strategy avoids the linear sequences reported in literature. The optical resolution has been exemplarily optimized for the 1-phenyl-1-sila-1,2,3,4-tetrahydronaphthalene derivative and the absolute configuration has been established by X-ray crystallography. The chiral auxiliary is stereospecifically displaced by simple reduction providing the highly enantioenriched silane (er = 98:2) which is enantiospecifically chlorinated as verified by a Walden inversion at silicon.

Phytotoxicity and ultrastructural effects of gymnopusin from the orchid Maxillaria densa on duckweed ( Lemna pausicostata) frond and root tissues

Two phenanthrene derivatives, characterized as erianthridin (9,10-dihydro-2,7-dihydroxy-3,4-dimethoxyphenanthrene) and gymnopusin (2,7-dihydroxy-3,4,9-trimethoxyphenanthrene), were isolated from an extract of the orchid Maxillaria densa, using phytotoxicity with amaranth ( Amaranthus hypochondriacus) to guide fractionation. Gymnopusin and erianthridin inhibited radicle elongation of A. hypochondriacus seedlings with IC 50 values of 330 and 58.2 μM, respectively. The phytoxicity of the two phenanthrene derivatives was also assessed on duckweed ( Lemna pausicostata), and compared with mammalian toxicity estimated in vitro with four mammalian cell lines. On duckweed, both phenanthrene derivatives caused electrolyte leakage, chlorophyll loss and photobleaching. Ultrastructural examination of duckweed frond and root tissues treated with gymnopusin (100 μM) revealed membrane damage to the tonoplast after 12 h of exposure. Effects on membrane integrity followed a time course similar to that of electrolyte leakage. Both phenanthrene derivatives exhibited moderate cytotoxicity to all mammalian cells tested, which precludes their use as a bioherbicide.

Emulsion copolymerization of vinyl acetate and butyl acrylate in the presence of fluorescent dyes

AbstractThis article describes our first experiments for preparing dye‐labeled latex particles by the emulsion copolymerization of a 4/1 (w/w) mixture of vinyl acetate‐butylacrylate (VAc‐BA). We discuss the synthesis of acrylate derivatives of phenanthrene, anthracene, and pyrene [9‐acryloxymethyl phenanthrene (7), 9‐acryloxymethyl‐10‐methyl anthracene (8), and 1‐acryloxymethyl pyrene (10)] and an allyl ether derivative of anthracene [9‐allyoxymethyl‐10‐methyl anthracene (9)]. Although the phenanthrene derivative 7 gave latex particles with high monomer conversion and good dye incorporation, the pyrene acrylate and both anthracene comonomers strongly inhibited the free‐radical reaction. To assist our search for a dye that would serve as a useful energy acceptor for phenanthrene and without suppressing VAc‐BA polymerization, we also examined batch emulsion polymerization in the presence of a variety of dye derivatives—substituted anthracenes, acridines, a coumarin, and two benzophenone derivatives. All of the anthracene derivatives, as well as acridine, strongly inhibited monomer polymerization. The coumarin dye 7‐hydroxy‐4‐methyl coumarin (22) that had only limited solubility allowed more than 90% monomer conversion. Most promising were 2‐hydroxy‐5‐methyl benzophenone (23) and 4‐N,N‐dimethylamino benzophenone (24) that at 1 mol % in the monomer mixture permitted virtually quantitative monomer conversion to latex. 4′‐Dimethylamino‐2‐acryloxy‐5‐methyl benzophenone (25) copolymerized well with the VAc‐BA mixture, yielding latex particles in high yield and with a narrow size distribution. These dyes appear to be useful acceptor dyes for energy‐transfer experiments with phenanthrene. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 1594–1607, 2002

Structural characterisation of humic acid-bound PAH residues in soil by [formula omitted]-CPMAS-NMR-spectroscopy: evidence of covalent bonds

The fate of 13 C -labelled phenanthrene and fluoranthene in different soil systems during biodegradation was studied. The soil humic acid fraction was isolated followed by structural characterisation using 13 C -cross polarisation magic angle spinning nuclear magnetic resonance spectroscopy ( 13C-CPMAS-NMR). It could be demonstrated that especially the ratio between the concentrations of polycyclic aromatic hydrocarbons (PAHs) and soil humus matrix limits the usefulness of this analytical tool. Based on these results a ratio of 13 C -activity PAH / 13 C -activity soil≈1.5/1.0 in the test material was suggested. The chemical transformation of a PAH and its bound residue formation in a soil system detected by changes of chemical shifts in the 13 C -NMR spectrum was proven for the first time. Structural information obtained by NMR spectra were verified by alkaline hydrolysis of PAH/humus-associations and following identification of cleavage products. Ester-bound phenanthrene metabolites such as 1-hydroxy-2-naphthoic acid, ortho-phthalic acid and 3,4-dihydroxybenzoic acid were detected. Additional structural assignments indicated the presence of ether-bound phenanthrene derivatives as well. Using isotopic labelling techniques a quantitative evaluation of bound residue distribution was undertaken. Fifty to seventy percent of phenanthrene metabolites which could be related to the added 13 C 1 -phenanthrene were ester bound via their carboxyl groups.

Two New Cyclic Bis(Bibenzyl)s, Isoriccardinquinone A and B from the Liverwort Marchantia Paleacea

From the 95% ethanol extract of the Hong Kong liverwort, Marchantia paleacea , guided by bioactivity directed isolation, two novel isoriccardinquinones A and B were obtained together with previously known marchantin C, isoriccardin C and phenanthrene derivative, 2-hydroxy-3,7-dimethoxyphenanthrene. The structures of the new compounds were established by high field spectroscopic methods, including 2D NMR techniques.

Phenanthrene derivatives from the orchid Coelogyne cristata

Coeloginanthridin, a 9,10-dihydrophenanthrene derivative, and coeloginanthrin, the corresponding phenanthrene analogue, were isolated from the orchid Coelogyne cristata which earlier afforded coelogin ( 1a) and coeloginin ( 1b). The structures of coeloginanthridin and coeloginanthrin were established as 3,5,7-trihydroxy-1,2-dimethoxy-9,10-dihydrophenanthrene ( 2a) and 3,5,7-trihydroxy-1,2-dimethoxyphenanthrene ( 2c), respectively, from spectral and chemical evidence including the conversion of coeloginanthridin triacetate ( 2b) to coeloginanthrin triacetate ( 2d) by dehydrogenation with DDQ. In the light of earlier reports on structurally similar compounds, 2a and 2c may have biological activities of phytoalexins and endogenous plant growth regulators.

Studies on quinones. Part 34: The reaction of styrene with activated 1,4-benzoquinones: access to potential antiprotozoal pyranobenzoquinones

Styrene reacts with highly electrophilic monosubstituted 1,4-benzoquinones to provide pyranobenzoquinone and phenanthrene derivatives, depending on the nature of the quinone substituent. The participation of transient Diels–Alder adduct intermediates in these reactions and their thermal-induced rearrangements are discussed. The in vitro antiparasital effects of the pyranobenzoquinones against Trypanosoma cruzi and Leishmania spp. are reported.

Flash vacuum pyrolysis of 3-aroylcinnolines: interesting routes toward polynuclear aromatic compounds

Flash vacuum pyrolysis of 3-aroylcinnolines 3 at 900°C and 0.02 Torr yielded phenanthrene and arylacetylene derivatives as the major products beside anthracene and diarylacetylene derivatives as minor products. Also, FVP of 3-(2-thienoyl)-cinnoline gave three isomeric naphthothiophenes, phenyl-2-thienylacetylene and phenylacetylene. On the other hand, 3-(2-furoyl)-cinoline gave dibenzofuran as a major product besides naphtho[1,2- b]furan and phenylacetylene.

Photoinduced electron transfer (ET) within some novel synthesized derivatives of phenanthrene acting as donors and 9-fluorenone/9-cyanoanthracene behaving as acceptors

With the help of both steady state and time-resolved measurements, possibilities of the occurrences of photoinduced electron transfer (ET) reactions within some novel synthesized derivatives of phenanthrene (1,1-dimethyl-9-methoxy-1,2,3,4-tetrahydrophenanthrene, 9MTHP; 1,1-dimethyl-6,9-dimethoxy-7-isopropyl-1,2,3,4-tetrahydrophenanthrene, 69DMTHP and 1,1-dimethyl-6,7,9-trimethoxy-1,2,3,4-tetrahydrophenanthrene, 679TMTHP) donors and 9-fluorenone/9-cyanoanthracene acceptors in acetonitrile fluid solution were studied at the ambient temperature (296 K). No ground state charge transfer complex was apparent from the observed electronic absorption spectra of the present reacting (D–A) systems. On singlet (S 1) excitation of acceptor moiety, low to moderate exothermic photoinduced ET reactions seem to be primarily responsible for the observed fluorescence quenching phenomena. Occurrence of such process within the excited acceptor and ground state donor was also confirmed from the measurement of transient absorption spectra at different delay times between the exciting and analyzing pulses. An attempt was made to test the Marcus theory both in the normal and inverted region for the photoinduced forward ET reactions within the donor and acceptor systems used in the present investigation.

Palladium-Catalyzed Controlled Carbopalladation of Benzyne

2-Trimethylsilylphenyl trifluoromethanesulfonate 1a, a benzyne precursor, reacted with the allylic chlorides 2a−f in the presence of CsF (2.0 equiv) and Pd2(dba)3·CHCl3 (2.5 mol %)−dppf (5 mol %) in a 1:1 mixed solvent of CH3CN and THF to produce the phenanthrene derivatives 3 along with their minor regioisomers 4 in good yields (i) and the reaction of 1a with 2a and the internal alkynes 15a,c−e afforded the naphthalene derivatives 16 in moderate yields (ii). The reaction of benzyne precursor 1a with the alkynes 15a−c,f−h in the presence of Pd(OAc)2 (5 mol %)−(o-tolyl)3P (5 mol %) catalyst and CsF (2.0 equiv) in CH3CN gave the phenanthrene derivatives 17 (iii), whereas the reaction of 1a with the alkynes 15a,b,i in the presence of the same catalysts and CsF in CH3CN−toluene gave the indene derivatives 18 in good yields (iv). Detailed mechanistic investigation revealed that the former two reactions i and ii proceed through carbopalladation to free benzyne, while the latter two reactions iii and iv proceed ...

The directed ortho metalation - palladium catalyzed cross coupling connection. A general regiospecific route to 9-phenanthrols and phenanthrenes. Exploratory further metalation

A new general and regiospecific synthesis of 9-phenanthrols (1 +2 [Formula: see text] 3 [Formula: see text] 4, Scheme 1, Table 1) proceeding by a Directed ortho Metalation (DoM), Suzuki-Miyaura cross coupling, and a new LDA-mediated Directed remote Metalation sequence is described. The facile Pd-catalyzed hydrogenolysis of the phenanthrols 4 into the corresponding phenanthrenes 5 via their triflates 18 translates the original DoM regioselectivity also into a general synthesis of phenanthrenes (Table 2). Further DoM (19 [Formula: see text]20, 21; 24 [Formula: see text]25), cross coupling (20c [Formula: see text]23), as well as oxidation - ring contraction (4b, 4f [Formula: see text]28a, 28b) chemistry of phenanthrene derivatives is reported.Key words: 9-phenanthrols, directed ortho metalation, Suzuki cross coupling, synthesis.

Plant Secondary Metabolites as Potential Anticancer Agents and Cancer Chemopreventives

A. Douglas KinghornProgram for Collaborative Research in the Pharmaceutical Sciences and Department of MedicinalChemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 SouthWood Street, Chicago, IL 60612, U.S.ATel.: (312) 996-0914, Fax: (312) 996-7107, E-mail: kinghorn@uic.eduThere is considerable interest in the screening of plant and other natural product extracts in moderndrug discovery programs, since structurally novel chemotypes with potent and selective biological ac-tivity may be obtained [1-4]. A consideration of biological activity in addition to the isolation andstructure elucidation stages in a phytochemical investigation may add a great deal to the overall scien-tific significance of the work. Phytochemists may gain considerable information by using panels ofsimple bioassays and/or more specialized in vitro bioassays to follow each step of a purification proce-dure [3]. In the following paragraphs, recent examples of bioactive compounds obtained in the author’slaboratory in projects directed towards the search for novel anticancer agents and cancer chemopre-ventives from higher plants will be presented.In the United States in 1999, it is estimated that over 1.2 million persons will be diagnosed with in-vasive forms of cancer, and over 1,500 people will die as a result of cancer each day [5]. Among manyrecent advances in cancer chemotherapy, plant natural products have played an important role in con-tributing to the arsenal of the approximately 60 cancer chemotherapeutic drugs on the market. For in-stance, in the United States, there are now four structural classes of plant anticancer agents available,constituted by the Catharanthus (Vinca) alkaloids (vinblastine, vincristine, vinorelbine), the epipodo-phyllotoxins (etoposide, etoposide phosphate, teniposide), the taxanes (paclitaxel and docetaxel), andthe camptothecin derivatives (irinotecan and topotecan) [6]. Several other plant-derived compoundsare currently in preclinical and clinical trials [6,7].As part of a National Cooperative Natural Products Drug Discovery Group (NCNPDDG) researchproject funded by the United States National Cancer Institute (1995-2000), our collaborative team atthe College of Pharmacy, University of Illinois at Chicago (Chicago, Illinois), and Research TriangleInstitute (Research Triangle Park, North Carolina), and Bristol-Myers Squibb (Princeton, New Jersey)is evaluating about 400 plant samples per year, with the aim of discovering and evaluating novel plant-derived anticancer agents. During the funding period 1990-1995, the industrial partner was GlaxoWellcome Medicines Research Centre (Sevenage, U.K.), and past progress made in the project hasbeen reviewed [8]. Since 1995, the primary plant samples have been collected in the Dominican Re-public, Peru, and Indonesia. Plant recollections have taken place mainly in Thailand and Zimbabwe in

Palladium-Catalyzed Intermolecular Controlled Insertion of Benzyne-Benzyne-Alkene and Benzyne-Alkyne-Alkene-Synthesis of Phenanthrene and Naphthalene Derivatives.

Aryne reagents, unlike alkynes, undergo insertion by allyl palladium complexes. The verification of the conversion described here is shown using Equation (1) as an example. The reaction proceeds in a few hours in refluxing acetonitrile to give the phenanthrene derivative in up to 71 % yield.