Unsubstituted Aromatic Ring Research Articles

Dihydrophenanthrenes and other antifungal stilbenoids from Stemona cf. pierrei

Three new dihydrophenanthrenes, stemanthrenes A–C, along with the new dihydrostilbene stilbostemin G were isolated and identified from the underground parts of Stemona cf. pierrei together with the known pinosylvin, 4′-methylpinosylvin, dihydropinosylvin, stilbostemins B, D, and E as well as the pyrrolo[1,2-a]azepine alkaloids protostemonine and stemonine. The structures of all new stilbenoids, elucidated by NMR analyses, showed a common substitution pattern for aromatic ring A and characteristic C-methylations for ring B. The trivial name racemosol, previously reported for S. collinsae, was renamed to stemanthrene D due to its priority for another compound. Bioautographic tests on TLC plates with Cladosporium herbarum displayed high antifungal activity for compounds with an unsubstituted aromatic ring A, e.g. pinosylvin, but only weak effects for the higher substituted stilbostemin G and stemanthrenes A–C. Similar results were obtained by germ tube inhibition of five microfungi using 2-fold serial broth dilutions determined by a microplate reader. Because of weak inhibition and chemical instability of stemanthrenes, no EC50 and EC90 values could be calculated.

Synthesis of 1-(3,4-dihydroxy-5-nitrophenyl)-2-phenyl-ethanone and derivatives as potent and long-acting peripheral inhibitors of catechol-O-methyltransferase.

A homologous series of novel nitro-catechol structures (7a-7e) were synthesized and tested as inhibitors of the enzyme catechol-O-methyltransferase (COMT). Increasing chain length was found to have significant impact on both brain penetration and duration of COMT inhibition in the rat. Of this series, compound 7b (1-(3,4-dihydroxy-5-nitrophenyl)-2-phenyl-ethanone) was found to exhibit the most potent and selective inhibition of peripheral COMT, with an inhibition profile more similar to entacapone 2 than tolcapone 1 (an equipotent peripheral and central inhibitor) but with much improved duration of action (7b, 70% inhibition and 2, 25% inhibition at 9 h after administration). The effects of structural modifications to 7b on COMT inhibitory profile were investigated, and it is concluded that the carbonyl group and preferably unsubstituted aromatic ring are essential features to maintain prolonged peripheral COMT inhibition. The introduction of the alpha-methylene group, the major structural difference between 7b and 1, would appear responsible for the observed enhancement in selectivity of peripheral COMT inhibition of 7b, which has more limited access to the brain than 1.

Suppression ofMonilinia fructicolacutinase production by peach fruit surface phenolic acids

Chlorogenic and caffeic acids are major phenolic acids in the epidermis and subtending cell layers of peach fruit (Prunus persica). Their concentrations are especially high in peach genotypes with a high level of resistance to the brown rot fungus,Monilinia fructicola, and decline as fruit mature with a corresponding increase in disease susceptibility. Chlorogenic acid and caffeic acid at concentrations up to 5 mmdid not inhibitM. fructicolaspore germination or mycelial growth in culture. In cultures amended with either of these phenolic acids, cutinase activity was reduced with a sharp decrease apparent at 0.1 mm. The presence of caffeic acid in cultures during growth on cutin prevented the appearance of two major cutinase isoforms as well as additional esterases in the filtrates. Cutinase activity was not directly inhibited by chlorogenic acid or caffeic acid, nor by oxidized caffeic acid. A series of cinnamic and benzoic acids with various degrees of hydroxylation and methoxylation of the aromatic ring also suppressed cutinase levels in culture, indicating the effect was not specific to the naturally abundant chlorogenic and caffeic acids. Cinnamic acid, with an unsubstituted aromatic ring, was least suppressive, and 2,3-dihydroxybenzoic acid, a known chelating agent that can facilitate iron transport, was most suppressive. We propose that the high concentration of chlorogenic acid present in immature fruit and in fruit from genotypes with high levels of disease resistance may contribute to the brown rot resistance of the tissue by interference with the production of factors involved in degradation of host polymers rather than by direct toxicity to the pathogen. Chlorogenic acid and related phenolics in combination with other factors such as iron could function to arrestM. fructicolain quiescent infections associated with immature and ripening fruit.

Mineralization of 4-Chlorodibenzofuran by a Consortium Consisting of Sphingomonas sp. Strain RW1 and Burkholderia sp. Strain JWS

The dibenzofuran-degrading bacterium Sphingomonas sp. strain RW1 (R.-M. Wittich, H. Wilkes, V. Sinnwell, W. Francke, and P. Fortnagel, Appl. Environ. Microbiol. 58:1005-1010, 1992) attacks 4-chlorodibenzofuran on the unsubstituted aromatic ring via distal dioxygenation adjacent to the ether bridge to produce 3(prm1)-chloro-2,2(prm1),3-trihydroxybiphenyl, which was identified by nuclear magnetic resonance spectroscopy and mass spectrometry. The compound is subsequently meta cleaved, and the respective intermediate is hydrolyzed to form a C-5 moiety, which is further degraded to Krebs cycle intermediates and to 3-chlorosalicylate. This dead-end product is released into the culture medium. A coculture of strain RW1 and the 3,5-dichlorosalicylate-degrading strain Burkholderia sp. strain JWS (A. Schindowski, R.-M. Wittich, and P. Fortnagel, FEMS Microbiol. Lett. 84:63-70, 1991) is able to completely degrade 4-chlorodibenzofuran with concomitant release of Cl(sup-) and formation of biomass.

2,4-Dinitrophenyl Phenyl Sulfone

The crystal structure of the title compound C12H8N2O6S, has been determined by single-crystal X-ray diffraction. The compound crystallizes in the noncentrosymmetric P21 space group. The substituted aromatic ring has a slightly deformed boat conformation. The o-NO2 and p-NO2 groups are twisted out of the plane of the phenyl ring. The unsubstituted aromatic ring is planar and the dihedral angle between the mean plane of the rings is 71.1 (2)°. Short C—H⋯O intermolecular contacts stabilize the three-dimensional structure.

Synthesis of potential receptor molecules by combination of upper‐rim‐functionalized calix[4]arenes and partly bridged resorcinarenes

AbstractCombination of upper‐rim‐1,3‐difunctionalized calix[4]arenes 14, 16, and 18 with tribridged resorcinarenes 4 and 6 and A,C‐di‐bridged resorcinarenes 10 and 13 yields both 1/1 calix‐resorcinarenes (22–24) and 2/1 calix‐resorcinarenes (25, 26). 1/1 Calix‐resorcinarene 22 mainly exists as one conformer (a), but at low temperatures (−60°C) very small amounts ( < 5%) of a second conformer (b) can be observed. Both conformers equilibrate via rotation about one of the C(arene)‐N bonds, with an activation free energy (Δ G≠) of 13 kcal/mol. 2/1 Calix‐resorcinarenes 25 and 26 are more flexible and exist as a mixture of conformers. In order to be able to rigidify the structure of 2/1 calix‐resorcinarenes via rigid spacers between the calix[4]arene fragments, 1,3‐diaminocalix[4]arene derivatives 31, 32, and 34 were synthesized carrying nitro, carboxylic ester, and cyano groups at the unsubstituted aromatic rings. With these calix[4]arene derivatives, three new, functionalized 2/1 calix‐resorcinarenes 35–37 have been synthesized.

1H and13C NMR studies on the antidepressant drug tianeptine

The conformational behaviour of 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c, f][1,2]thiazepin-11-yl)amino] heptanoic acid 5,5 dioxide (tianeptine), a new antidepressant drug, was studied by means of 1H and 13C NMR. The ring skeleton exhibits two distinct conformations at low temperature. The conformational exchange is still restricted at room temperature, particularly in the solvents D2O and CDCl3, where significant aggregation of the molecules occurs. The side-chain seems to adopt a preferential conformation where it is bent over the unsubstituted aromatic ring. This conformational preference in the biologically active structure might be related to the observed loss of activity when substituents are introduced on the aromatic rings.

Application of deuteriated isotopomers in the analysis of 13C CP/MAS NMR spectra of some azo dyes

Abstract13C CP/MAS NMR spectra (50.3 MHz) of 4‐[N,N‐bis(2‐hydroxyethyl)amino]azobenzene (1), (N,N‐dimethylamino)azobenzene (2), 4‐methoxyazobenzene (3), 2‐hydroxy‐5‐tert‐butylazobenzene (4) and 4‐hydroxyazobenzene (5) were recorded. The isotopomers of 1, 4 and 5 with pentadeuteriated unsubstituted aromatic rings were also studied. Dipolar dephased spectra of the deuteriated isotopomers were used for chemical shift interpretation in the solid state. The changes in cross‐polarization dynamics caused by deuteration were investigated for 1. The spectra of 1, 2, 3, and 5 were also measured at elevated temperature. It was found that in 1, 2 and 5, rotation of the aromatic rings is induced at elevated temperature.

Carbon‐13 Nuclear Magnetic Resonance Spectra of Soil Humic Substances Extracted by Different Mechanisms

AbstractHumic substances were extracted from an organic soil of Tuscany, Italy, with solutions operating by three different mechanisms: charge repulsion (NaOH under N2), ligand exchange (Na4P2O7 at pH = 7), and H‐bond disruption (dipolar aprotic solvents in mixture with dilute HCl). Solution‐state 13C‐nuclear magnetic resonance (NMR) spectra were obtained for the unpurified and purified (HCl‐HF treatment) extracts, revealing that humic matter obtained through the H‐bond‐disruption mechanism was different from materials extracted using the two other mechanisms. Extracts obtained using dipolar aprotic solvents (DMF, DMSO, acetone) showed better resolved spectra than those using NaOH and Na4P2O7. This was due to a lower content of coextracted silicate materials and lower molecular weights. Spectra of humic substances extracted with acetone and DMF had a higher percentage of aliphatic C than did the spectrum of the extract with DMSO. The latter was, in general, more similar to the spectra of stronger extractants. The H‐bond‐disruption mechanism of dipolar aprotic solvents appeared to have extracted more unsubstituted aromatic rings than NaOH and Na4P2O7, although percent of aromatic C was generally equivalent in the spectra of all extractants. Purification with a HCl‐HF treatment decreased mainly the content of aliphatic, carbohydrate, and amino acid components of all extracts. Poor agreement between values for total acidity of extracts calculated by NMR and those given by chemical methods was also observed in this study.

Gold(III) complexes with nitriles containing aromatic nuclei: crystal and molecular structure of trichloro(p-toluonitrile)gold(III)

Anhydrous gold(III) chloride reacts with nitriles to give complexes of the type [AuCl3(NCR)](R = C6H4CH3-p, CH2C6H5, or C6H5), in spite of the ability of gold(III) chloride to metallate unsubstituted or methyl-substituted aromatic rings. An X-ray diffraction study of the p-toluonitrile derivative at 190 K confirmed that the product is a gold(III) end-on nitrile complex with gold in its usual square co-ordination. The product crystallizes in the monoclinic space group P21/n, with a= 6.669(2), b= 12.574(3), c= 13.740(3)A, β= 90.30(2)°, and Z= 4. Refinement converged to R= 0.021 for 1 246 independent ‘observed’ reflections. The Au–Cl bond lengths are 2.236(2) and 2.284(2), 2.271(2)A for the chlorine atom trans to the nitrile and for the cis chlorines, respectively; Au–N 1.980(6)A. Complexes of formula AuCl2(NCR)(R = C6H4CH3-p or CH2C6H5), obtained with a large excess of the nitrile and over long reaction times, are suggested to be, on the basis of spectroscopic data, ionic mixed-valence species of the type [AuCl2(NCR)2][AuCl2].

6- 211At-Astato-2-methyl-1,4-naphthoquinol bis (disodium phosphate): A novel α-emitting potential anti-tumour drug

6- 211At-Astato-2-methyl-1,4-naphthoquinol bis (disodium phosphate) has been prepared as a potential endoradiotherapeutic drug for metastatic malignant disease. Astatine-211 was introduced into the unsubstituted aromatic ring of 2-methyl-1,4-naphthoquinone via the 6-chloromercuriderivative; the 5-stage synthesis was completed within one half-life. Overall radiochemical efficiency ranged from 28–32%, with a specific activity 3.5–3.7 μCi μmol −1 from 200 μCi 211At.

Investigation of the lability of furan and its derivatives in nucleophilic substitution reactions by the mindo/3 method

The a complexes of furan, thiophene, pyrrole, pyridine, and benzene with the hydride ion were calculated by the MINDO/3 method. The affinities of the indicated aromatic rings and a number of substituted furans for the H− ion were estimated. It is shown that the relative magnitude of the affinity correlates qualitatively with the experimental data on the relative rates of the reaction of the examined compounds with nucleophilic reagents. The following order of increasing reactivities of unsubstituted aromatic rings was obtained: pyrrole<furan<benzene< pyridine≤thiophene. The effect of various types of substituents in various positions on the tendency of the five-membered ring to undergo nucleophilic substitution is discussed.

π-Arene-π-cyclopentadienyliron cations from some substituted naphthalenes

Reaction of 1-fluoro-, 1-choloro- or 1-bromo-napthalene with ferrocene and AlCl 3/Al in refluxing cyclohexane gave the π-1-halophthalene-π-cyclopenta-dienyliron cation (III, IV or V) in which the (Cp)Fe group is complexed only to the unsubstituted aromatic ring. A similar reaction with 2-methylnaphthalene, however, gave rise to both π-2-methylnaphthalene-π-cyclopentadienyliron cations in which either the substituted or the unsubstituted aromatic ring was complexed to (Cp)Fe. With 1-bromonaphthalene under these reaction conditions, in addition to ion V, both the dehalogenated π-naphthalene-π-cyclopentadienyliron cation (I) and the hydrogenated π-tetralin-π-cyclopentadienyliron cation(II) were obtained. When the reaction was carried out in the presence of I 2 or DPPH as radical scavenger, the formation of II was eleiminated, thus strongly implicating radical reactions in the hydrogenation process. Moreover, ehwn perdeuteronaphthalene was converted to II, extensive H— exchanges were observed. To acount for these results, a hydrogenation mechanism involving radical ions as key intermediates is proposed.

Aromatic amino acid transport in Yersinia pestis

The uptake and concentration of aromatic amino acids by Yersinia pestis TJW was investigated using endogenously metabolizing cells. Transport activity did not depend on either protein synthesis or exogenously added energy sources such as glucose. Aromatic amino acids remained as the free, unaltered amino acid in the pool fraction. Phenylalanine and tryptophan transport obeyed Michaelis-Menten-like kinetics with apparent Km values of 6 x 10(-7) to 7.5 x 10(-7) and 2 x 10(-6) M, respectively. Tyrosine transport showed biphasic concentration-dependent kinetics that indicated a diffusion-like process above external tyrosine concentrations of 2 x 10(-6) M. Transport of each aromatic amino acid showed different pH and temperature optima. The pH (7.5 TO8) and temperature (27 C) optima for phenylalanine transport were similar to those for growth. Transport of each aromatic amino acid was characterized by Q10 values of approximately 2. Cross inhibition and exchange experiments between the aromatic amino acids and selected aromatic amino acid analogues revealed the existence of three transport systems: (i) tryptophan specific, (ii) phenylalanine specific with limited transport activity for tyrosine and tryptophan, and (iii) general aromatic system with some specificity for tyrosine. Analogue studies also showed that the minimal stereo and structural features for phenylalanine recognition were: (i) the L isomer, (ii) intact alpha amino and carboxy group, and (iii) unsubstituted aromatic ring. Aromatic amino acid transport was differentially inhibited by various sulfhydryl blocking reagents and energy inhibitors. Phenylalanine and tyrosine transport was inhibited by 2,4-dinitrophenol, potassium cyanide, and sodium azide. Phenylalanine transport showed greater sensitivity to inhibition by sulfhydryl blocking reagents, particularly N-ethylmaleimide, than did tyrosine transport. Tryptophan transport was not inhibited by either sulfhydryl reagents or sodium azide. The results on the selective inhibition of aromatic amino acid transport provide additional evidence for multiple transport systems . These results further suggest both specific mechanisms for carrier-mediated active transport and coupling to metabolic energy.

Thio-analogues of Meisenheimer complexes

The first gem-di(alkylthio)-analogue of Meisenheimer complexes is obtained in equilibrium with, and is appreciably less stable than, the addition complex at an unsubstituted aromatic ring carbon when ethyl thiopicrate is mixed with sodium ethanethiolate in Me2SO; both complexes are transient species because of specific rapid replacement of the p-nitro-group by ethanethiolate.