Microbial degradation of 1,3-dichlorobenzene

A gram-negative, peritrichously flagellated rod, tentatively identified as an Alcaligenes sp., was isolated from a mixture of soil and water samples by using 1,3-dichlorobenzene as the sole carbon and energy source. During growth on 1,3-dichlorobenzene, almost stoichiometric amounts of chloride were released. Simultaneous adaptation studies, as well as enzyme studies, indicated that 1,3-dichlorobenzene was metabolized via 3,5-dichloro-cis-1,2-dihydroxycyclohexa-3,5-diene to 3,5-dichlorocatechol. Subsequently, the latter product was cleaved, yielding 2,4-dichloromuconate. No initial hydrolytic step yielding 3-chlorophenol was detected in this species.     

Microbial degradation of 1,3-dichlorobenzene.

A gram-negative, peritrichously flagellated rod, tentatively identified as an Alcaligenes sp., was isolated from a mixture of soil and water samples by using 1,3-dichlorobenzene as the sole carbon and energy source. During growth on 1,3-dichlorobenzene, almost stoichiometric amounts of chloride were released. Simultaneous adaptation studies, as well as enzyme studies, indicated that 1,3-dichlorobenzene was metabolized via 3,5-dichloro-cis-1,2-dihydroxycyclohexa-3,5-diene to 3,5-dichlorocatechol. Subsequently, the latter product was cleaved, yielding 2,4-dichloromuconate. No initial hydrolytic step yielding 3-chlorophenol was detected in this species.     

Solid-phase synthesis of chiral stationary phases based on 2,4,5,6-tetrachloro-1,3-dicyanobenzene derivatives spaced from N-3,5-dinitrobenzoyl alpha-amino acids: comparative study of their resolution efficacy

Two new chiral stationary phases, 3-[5-chloro-1,3-dicyano-2,4-[2'-(N'-1,3-dinitrobenzoyl-D-phenylglycinyl) aminoethyl]aminophen-1-yl] aminopropyl silica (CSP-1) and 3-[5-chloro-1,3-dicyano-2,4-[2'-(N'-1,3-dinitrobenzoyl-L-leucinyl) aminoethyl] aminophen-1-yl] aminopropyl silica (CSP-2), were prepared by solid-phase synthesis. They comprise chiral unit, 3,5-dinitrobenzoyl derivative of the amino acid, D-PhGly or L-Leu, bound via spacer 1,2-diaminoethane to 2,4-positions of the persubstituted benzene ring, derived from compound 1, and possess pseudo-C2 symmetry. Preparation of model compounds 6 and 7 confirmed the structure of chiral selectors, which comprise pi-donor persubsituted aromatic ring and two strong pi-acceptor 3,5-dinitrobenzoyl amido units. CD spectra of model selectors 6 and 7, run in DMSO above 250 nm, exhibit negative exciton coupling (EC) between pi-acceptor and pi-donor chromophores, C(1) symmetric model compound 8 exhibited much weaker EC and 9, devoid of pi-donor unit, does not exhibit any significant CD. Combined pi-donor and pi-acceptor properties enable the new CSPs to separate a broad range of racemates. The columns with CSP-1 and CSP-2 were tested for the separation of 22 racemates by HPLC with two different mobile phase systems and the results are compared with those obtained by using a structurally related commercial column.     

Endoplasmic Reticulum (ER) Stress-Suppressive Compounds from Scrap Cultivation Beds of the Mushroom Hericium erinaceum

Four compounds were isolated from scrap cultivation beds of the mushroom, Hericium erinaceum. Compounds 1–4 were identified as methyl 4-hydroxy-3-(3-methylbutanoyl) benzoate, 2-chloro-1,3-dimethoxy-5-methylbenzene, methyl 4-chloro-3,5-dimethoxybenzoate, and 4-chloro-3,5-dimethoxybenzaldehyde by an interpretation of the NMR and MS data, respectively. This is the first reported isolation of 1 from a natural source. All the compounds showed protective activity against endoplasmic reticulum stress-dependent cell death.     

Regio- and stereo-selective synthesis of carbohydrate isoxazolidines by 1,3-dipolar cycloaddition of nitrones to 5,6-dideoxy-1,2-O-isopropylidene- alpha-D-xylo-hex-5-enofuranose.

The synthesis of 2-phenyl-3-aryl and 2-phenyl-3-aroyl derivatives 5-(1,2-O-isopropylidene-alpha-D-xylo-tetrofuranos-4-yl)isoxazolidi ne (3) from nitrones and 5,6-dideoxy-1,2-O-isopropylidene-alpha-D-xylo-hex-5- enofuranose (1) is described. The 1,3-dipolar cycloaddition reactions given mainly anti adducts 3 and 4 (greater than or equal to 95% pi-facial stereoselectivity). The cycloadducts 3 with H-3,5 cis are formed either exclusively or preponderate over the trans diastereoisomers 4.     

Degradation mechanisms of phenolic beta-1 lignin substructure model compounds by laccase of Coriolus versicolor

Phenolic beta-1 lignin substructure model compounds, 1-(3,5-dimethoxy-4-hydroxy-phenyl)-2-(3,5-dimethoxy-4-ethoxyphenyl)propa ne-1, 3-diol (I) and 1-(3,5-dimethoxy-4-ethoxyphenyl)-2-(3, 5-dimethoxy-4-hydroxyphenyl)propane-1,3-diol (II) were degraded by laccase of Coriolus versicolor. Substrate I was converted to 1-(3,5-dimethoxy-4-hydroxyphenyl)-2-(3,5-dimethoxy-4-ethoxyphenyl)-3- hydroxypropanone (III), 1-(3,5-dimethoxy-4-ethoxyphenyl)-2-hydroxyethanone (IV), syringaldehyde (V), 1-(3,5-dimethoxy-4-ethoxyphenyl)-3-hydroxypropanal (VI), 2,6-dimethoxy-p-hydroquinone (VII), and 2,6-dimethoxy-p-benzoquinone (VIII). Furthermore, incorporations of 18O of 18O2 into ethanone (IV) and 18O of H218O into hydroquinone (VII) and benzoquinone (VIII) were confirmed. Substrate II gave 1-(3,5-dimethoxy-4-hydroxyphenyl)ethane-1, 2-diol (IX), 1-(3,5-dimethoxy-4-hydroxyphenyl)-2-hydroxyethanone (X), and 3,5-dimethoxy-4-ethoxybenzaldehyde (XI). Also 18O of H218O was incorporated into glycol (IX) and ethanone (X). Based on the structures of the degradation products and the isotopic experiments, it was established that three types of reactions occurred via phenoxy radicals of substrates caused by laccase: (i) C alpha-C beta cleavage (between C1 and C2 carbons); (ii) alkyl-aryl cleavage (between C1 carbon and aryl group); and (iii) C alpha (C1) oxidation.     

Anthraquinones in callus cultures of Cinchona ledgeriana

From callus cultures of Cinchona ledgeriana seven known anthraquinones, purpurin, anthragallol-1,2-dimethylether, anthragallol-1,3-dimethylether, rubiadin, 1-hydroxy-2-hydroxymethylanthraquinone, 1-hydroxy-2-methylanthraquinone and morindone-5-methylether (or 1,7-dihydroxy-8-methoxy-2-methylanthraquinone), and eight new anthraquinones, 5,6-dimethoxy-1-(or -4-)hydroxy-2-(or -3-)hydroxymethylanthraquinone, 5-methoxy-2-(or -3-)methyl-1,4,6-trihydroxyanthraquinone, 2-hydroxy-1,3,4-trimethoxyanthraquinone, 4-methoxy-1,3,5-trihydroxyanthraquinone, 1,4-dimethoxy-2,3-methylenedioxyanthraquinone, 1,3-dihydroxy-4-methoxyanthraquinone, 1,3-dihydroxy-2,5-dimethoxyanthraquinone and 2,5-(or 3,5-)dihydroxy-1,3,4-(or -1,2,4-)trimethoxyanthraquinone have been isolated.     

Necrodane monoterpenoids from Lavandula luisieri

Four new irregular monoterpenoids were identified in the essential oil of Lavandula luisieri (Rozeira) Riv. Mart., a Labiatae endemic to the Iberian Peninsula. By means of spectroscopic and chemical methods, they were characterised as 3,5-dimethylene-1,4,4-trimethylcyclopentene, 5-methylene-2,3,4,4-tetramethylcyclopent-2-enone, 3,4,5,5-tetramethylcyclopenta-1,3-dienecarboxaldehyde and 3,4,5,5-tetramethylcyclopenta-1,3-dienecarboxylic acid. L. luisieri essential oil and extract showed a good activity against Candida albicans and gram positive bacteria: Staphylococcus aureus, S. epidermidis and S. pyogenes.     

Non-inducibility of the glutathione transferases of the earthworm Eisenia andrei

1. Earthworms were exposed to solutions of potential biotransformation enzyme inducers, i.e. trans-stilbene oxide (0.1 mM), 3-methylcholanthrene (50 μM) or 1,4-bis[2-(3,5-dichloropyridoxyl)]benzene (30 μM) for 1 hr each day in three successive days.2. Glutathione transferase (GST) was determined in cytosolic extracts of the worms the day after the last treatment, with chloro-2,4-dinitrobenzene, l,2-dichloro-4-nitrobenzene and ethacrynic acid as electrophilic substrates. Activity toward 1,2-epoxy-3-[p-nitro-fenoxy]propane was not detected.3. With all three substrates, the specific activity in the cytosol was similar in treated animals and controls.4. Ion exchange chromatography was performed on a NeoBar AQ^TMcolumn (The “Low Pressure High Performance” technique), and GST eluted in four distinct peaks.5. The elution profiles of GST activity were almost identical for exposed earthworms and controls.6. The results suggest that earthworms may not have inducible GST, perhaps because they are detritus eaters, and do not need to detoxicate poisonous secondary plant metabolites.     

巴戟天中蒽醌类化合物及生物活性研究

采用硅胶柱层析结合制备液相从巴戟天(Morinda officinalis)中分离得到8个蒽醌类化合物。根据化合物的波谱数据并与文献对照进行了结构鉴定,分别为2-羟甲基-3-羟基蒽醌(2-hydroxymethyl-3-hydroxyanthraquinone,1)、3-羟基-2-羟甲基-1-甲氧基蒽醌(3-hydroxy-2-hydroxymethyl-1-methoxyanthraquinone,2)、2-羟基-1-甲氧基蒽醌(2-hydroxy-1-methoxyanthraquinone,3)、3-羟基-1,2-二甲氧基蒽醌(3-hydroxy-1,2-dimethoxyanthraquinone,4)、甲基异茜草素-1-甲醚(rubiadin-1-methyl ether,5)、1,3-二羟基-2-甲氧基蒽醌(1,3-dihydroxy-2-methoxyanthraquinone,6)、1,3-二羟基-2-乙氧甲基蒽醌(ibericin,7)、1,2-二羟基-3-甲基蒽醌(1,2-dihydroxy-3-methylanthraquinone,8)。其中蒽醌(2)为首次从该植物中分得。利用MTT法对分离出的蒽醌的体外抗癌活性进行筛选,结果显示蒽醌(3)、(5)和(7)对肝癌细胞SMMC-7721增殖有明显的抑制作用,当蒽醌的浓度为400μmol/L时,蒽醌(3)、(5)和(7)对肝癌细胞的抑制率分别为44. 63%、20. 52%、54. 89%。     

Synthesis and biological evaluation of some novel N-aryl-1,4-dihydropyridines as potential antitubercular agents

1,4-Dihydropyridines are the emerging class of antitubercular agent. Recently, studies have revealed that 1,4-dihydropyridine-3,5-dicarbamoyl derivatives with lipophilic groups have demonstrated excellent antitubercular activity. We have synthesized new N-aryl-1,4-dihydropyridines bearing carbethoxy and acetyl group at C-3 and C-5 of the DHP ring. In addition, 1H-pyrazole ring is substituted at C-4 position. The lowest minimum inhibitory concentration value, 0.02 μg/mL, was found for diethyl 1-(2-chlorophenyl)-1,4-dihydro-2,6-dimethyl-4-(1,3-diphenyl-1H-pyrazol-4-yl)pyridine-3,5-dicarboxylate 4e making it more potent than first line antitubercular drug isoniazid. In addition, this compound exhibited relatively low cytotoxicity.     

Enantioseparation of 2-aryl-1,3-dicarbonyl analogues by high performance liquid chromatography using polysaccharide type chiral stationary phase

The HPLC chiral separation of 21 kinds of 2-aryl-1,3-dicarbonyl analogues was investigated in normal phase mode with amylose tris(3,5-dimethylphenylcarbamate), amylose tris((S)-1-phenylethylcarbamate), cellulose tris(3,5-dimethylphenylcarbamate), and cellulose tris(4-methylbenzoate) chiral stationary phases, respectively. The whole set of 2-aryl-1,3-dicarbonyl analogues shows better enantioselectivity and enantioseparation on amylose tris(3,5-dimethylphenyl carbamate) (Chiralpak AD-H). The temperature dependence of enantioselectivity was studied to improve the enantioseparation. In addition, efforts are made to relate analyte structure with the quality of the achieved chiral separation.     

New hydroxystilbenoid derivatives endowed with neuroprotective activity and devoid of interference with estrogen and aryl hydrocarbon receptor-mediated transcription

We have synthesized a series of new (E) stilbenoid derivatives containing hydroxy groups at ring positions identical or similar to those of trans-resveratrol and bearing one or two bulky electron donating groups ortho to 4′-OH and we have evaluated their neuroprotective activity using glutamate-challenged HT22 hippocampal neurons to model oxidative stress-induced neuronal cell death. The most active derivatives, 5-{(E)-2-[3,5-bis(1-ethylpropyl)-4-hydroxyphenyl]ethenyl}-1,3-benzenediol (2), 5-[(E)-2-(3,5-di-tert-butyl-4-hydroxyphenylethenyl)]-1,3-benzenediol (4) and 5-{(1E,3E)-4-[3,5-bis(1-ethylpropyl)-4-hydroxyphenyl]-1,3-butadienyl}-1,3-benzenediol (6), had EC₅₀ values of 30, 45 and 12 nM, respectively, and were ca. 100 to 400-fold more potent than resveratrol. Derivatives 2, 4 and 6 lacked cytotoxic activity against HT22 cells and estrogen receptor agonist or antagonist activity in estrogen response element-dependent gene expression and in estrogen-dependent proliferation of MCF-7 human breast cancer cells. In addition, they were incapable of interfering with aryl hydrocarbon receptor-mediated xenobiotic response element-dependent gene expression. Derivatives 2, 4 and 6 might assist in the development of lead candidates against oxidative stress-driven neurodegenerative diseases that will not increase endocrine cancer risk nor affect drug activation and detoxification mechanisms.     

Preparation, spectroscopy, X-ray analysis, and water-solubility studies of the first bis-PTA (PTA = 1,3,5-triaza-7-phosphaadamantane) derivatives

The bis-phosphines, 1,1′-[1,2-phenylenebis(methylene)]bis-3,5-diaza-1-azonia-7-phosphatricyclo[3.3.1.1]decane dibromide (1), 1,1′-[1,3-arenebis(methylene)]bis-[3,5-diaza-1-azonia-7-phosphatricyclo [3.3.1.1]decane dibromide (arene = phenyl (2), tolyl (3), anisolyl (4)), and 1,1′-[1,4-phenylenebis(methylene)]bis-3,5-diaza-1-azonia-7-phosphatricyclo[3.3.1.1]decane dibromide (5) were prepared in over 90% yield by refluxing 1,2-bis(bromomethyl)benzene, 1,3-bis(bromomethyl)benzene, 1,3-bis(bromomethyl)-5-methyl-benzene, 1,3-bis(bromomethyl)-5-methoxy-benzene, and 1,4-bis(bromomethyl)benzene with 1,3,5-triaza-7-phosphaadamantane (PTA) in acetone or chloroform. Compounds 1-5 are the first phosphines reported that contain two PTA moieties. All five compounds were characterized by ESI-MS, elemental analysis, ¹H, ¹³C, and ³¹P NMR spectroscopy, while 3 and 4 were additionally analyzed via single crystal X-ray diffraction. The relative positions of the PTA units on the aromatic ring as well as the substituents of the ring had a pronounced effect on the water-solubilities of the systems. The ortho compound (1, 2000 mg/mL) was more than two orders of magnitude more soluble than the para compound (5, 12.5 mg/mL). The meta substituted phenyl (2) and tolyl (3) compounds had solubilities (810 mg/mL) that were more than triple that of PTA (235 mg/mL) while the anisolyl analog (4) was half as soluble (121 mg/mL).     

The resolution of five racemic alpha-lactams by HPLC

The resolution of five racemic alpha-lactams (1a-d,g) using HPLC is reported. Five different Pirkle-type stationary phases were tested. The enantiomers of alpha-lactams containing the trityl group (1a-d) were separated (selectivity factors ranging from 1.08 to 1.20) using a mobile phase of hexane/2-propanol:98/2 and a stationary phase consisting of the 3,5-dinitroaniline derivative of (S)-valine with a urea linkage. Among the dialkyl-substituted alpha-lactams (1e-g), only 1,3-di-tert-butylaziridinone (1g) could be resolved, but only partially (selectivity factor = 1.07), with a mobile phase of hexane/1,2-dichloroethane:95/5 and the stationary phase consisting of the 3,5-dinitrobenzoic acid derivative of (R)-1-naphthylglycine.     

Synthesis and absolute configuration assignment of 5-amino-1,3,5-triphenyl-pentane-1,3-diol stereoisomers

Starting from 2,4,6-triphenylpyrylium perchlorate, 5-amino-1,3,5-triphenyl-pentane-1,3-diol stereoisomers 4 were obtained in a simple two-step synthesis: reaction with hydroxylamine, and reduction with LAH of the resulting 2-isoxazoline ketone derivative 2. The eight stereoisomers of 4 were separated in a single shot on a chiral stationary phase cellulose tris(3,5-dimethylphenylcarbamate) (Chiralcel OD-H). The absolute configuration of the title compounds, intermediate 2-isoxazoline ketone 2 and isoxazoline alcohol derivative 3 were determined using a combination of diastereoselective synthesis, affiliation of the sign in chemical interconversion method, and X-ray determination. 2-Isoxazoline ketone 2 enantiomers and isoxazoline alcohol 3 enantiomers were obtained by chiral HPLC on Chiralpak AD column. 2-Isoxazoline ketone 2 enantiomers can be racemized via a retro Michael addition.     

Larvicidal isoxazoles: Synthesis and their effective susceptibility towards Aedes aegypti larvae

Twenty 3,5-disubstituted isoxazoles have been synthesized and tested against fourth instar Aedes aegypti larvae. In the synthesis of title compounds, modifications have been made in the C-5 side-chain with a view to test their larvicidal activity. These isoxazoles have been obtained by 1,3-dipolar cycloaddition of arylnitrile oxides to terminal alkynes which furnished the desired products in 20% to 79% yields. A comparative study of the larvicidal activity between 3-(3-aryl-isoxazol-5-yl)-propan-1-ols and 3-(3-aryl-isoxazol-5-yl)-propionic acids clearly demonstrated that the latter compounds possess much better larvicidal activity than the former. We also tested two esters, viz., methyl 3-[3-(phenyl)-isoxazole-5-yl] propionate and methyl 3-[3-(4-chlorophenyl)-isoxazole-5-yl] propionate, where the latter presented an excellent larvicidal profile.     

Stereochemically controlled transformations related to pyrimidine nucleosides and their analogues

The diastereoisomeric differentiations and anomerizations of 5,6-dihydrothymidine and its anhydro derivatives were studied. In particular, the oxetane ring opening of (5S)-1-(3,5-anhydro-2-deoxy-beta-D-threopentofuranosyl)-5,6-dihydr othymine under acid catalysed conditions substantiated a number of the configurational modifications at the sugar moiety. The 1,3-dipolar cycloaddition to the pyrimidine C(5), C(6)-double bond was intramolecularly facilitated by the activation of 1-(3-azido-2-hydroxypropyl)uracil. (E)- and (Z)-1-Prop-enyl- and properly functionalized 1-propyl-uracil derivatives were also prepared and used for the synthesis of the tetrahydro-oxazolo[3,2-c]pyrimidine-5,6-(4H, 6H)dione and 9,3'-cyclo-3-propyl (or prop-1-enyl)-8-azaxanthine derivatives.     

Formation and metabolism of 3',5'-diiodothyronine and 3,5-diiodothyronine by cultured monkey hepatocarcinoma cells.

Cultured monkey hepatocarcinoma cells were incubated with [3',5'-125I] diiodo-L--thyronine and with [3,5-125I] diiodo-L-thyronine. In both instances monodeiodination as well as sulfoconjugation took place. [3.-125I] iodothyronine and [3',5'-125I] diiodothyronine were identified as metabolites of [3'-5'-125I]-L-thyroxine in the cells, but neither [3-125I]-iodothyronine nor [3,5-125I] diiodothyronine was detected after incubation of the cells with ]3,5-125I]-L-thyroxine. No products of diphenyl ether splitting were observed in the medium after incubation of the cells with either [3,5-125I] diiodo-L-thyronine or [3,5-125I]-L-thyroxine.     

Scilla bifolia Wax as a Source of Diverse Long-Chain Resorcinols and Alkane-1,3-diols

GC, GC/MS and NMR analyses of Scilla bifolia washings allowed for the identification of thirty-six long-chain compounds belonging to six homologous series (five of which are from the class of resorcinols, a group of biologically important phenols): 1-alkyl-3,5-dimethoxybenzenes, 5-alkyl-3-methoxy-2-methylphenols, 3-alkyl-5-methoxyphenols, 5-alkyl-2-methylresorcinols (five compounds from each of the series); 5-alkylresorcinols (six compounds) and 1,3-alkanediols (ten compounds). Many of these compounds rarely occur in Nature. Retention indices of these compounds, as well as indices of the corresponding trimethylsilyl derivatives, were reported, some of them for the first time. The exact regiochemistry was unambiguously determined by two-dimensional NMR experiments; in some cases, the complete NMR assignment was augmented by computer spin-simulation of ¹H-NMR spectra.