Synthesis of 1-Benzoyl-3-aryl-4-hydroxy-4-phenylimidazolidin-2-thiones

l-Benzoyl-3-aryl-4-hydroxy-4-phenylimidazolidin-2-thiones can be synthesized readily from the cyclization of 1-benzoyl-3-arylthioureas with bromine-acetophenone in the presence of excess triethylamiqe.     

Crystal Structure of Loliolide (5, 6,7a-Tetrahydro-6-hydroxy-4, 4, 7a-trimethyl-2 (4H)-benzofuranones)

1INTRODUCTIONThetitlecompound,C,,H,,O,(mp:146～148'C),forthefirsttime,wasiso-latedfromClinopodiumpolycephalum(Vant-)byC.Y.WuetHsuancalled"DuanXueliu"inChinesethatisusedinfolkmedicineforthetreatmentofhaemorrhagiadisease[1i.Itsstructurehasalreadybeendeterminedt2ibymeansofUV,lR,NMRandchemicalsynthesis.Sinceloliolideappearedtohaveantitumoractivity"'andim-munosuppressiveactivity'#'inrecentyears,weaffirmedthestructurebyX-raydiffractionanalysis.2EXPERIMENTALApaleyellowtransparentcry…     

Crystal Structure of 2-（2-Carboxy-4-hydroxy-6- methoxyphenoxy）-3,5-dichloro-6-hydroxy- 4-methylbenzoic Acid 1-Methyl Ester

The title compound, neogeodin hydrate （C17H14C1208, CAS： 94540-50-8）, was derived from marine fungus Aspergilhts terreus CRIM301. It was unequivocally characterized by IR, NMR spectroscopies, and single-crystal X-ray crystallography and tested for various biological activities. Neogeodin hydrate crystallizes in the triclinic space group P1 with a = 8.1159（5） A, b = 8.2472（4） A, c= 14.1278（7） A, a = 81.448（2）°, β = 84.860（2）°, γ= 70.400（2）°, V = 880.13（8） A3; Z = 2. It comprises a diphenyl ether, asterric acid skeleton and dichloro substituents. The methoxyphenoxy rings of the inversely related molecules form a ribbon-like structure that is stabilized by O-H...O hydrogen bonds through the doubly disordered carboxyl groups and by C-H...O interactions, generating the same R22（8） ring motif. The chlorinated methylbenzoate rings, making mostly a right angle, link the parallel upper and lower ribbons via bifurcated O-H...O and C-H...O hydrogen bonds, yielding endless channels. The channels formed are further sustained by C-H...O and π...π interactions Neogeodin hydrate exhibits inhibition against superoxide anion radical formation in the xanthine/xanthine oxidase （XXO） assay, but has no aromatase inhibitory activity.     

Amino acid derivatives of 2-R-7-hydroxy-3′,4′-ethylenedioxyisoflavones

A number of 7-O-aminoacyl derivatives of isoflavones have been obtained by the interaction of 2-R-7-hydroxy-3,4-ethylenedioxyisoflavones with the symmetrical anhydrides of N-protected amino acids.Kiev Tara Shevshenko University, Ukraine, 252033, Kiev, Ul. Vladimirskaya, 64, tel./fax 225-12-73. Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp. 334–338, May–June, 1999.     

Microwave-assisted,methanesulfonic acid-catalyzed synthesis of 3,3′-(arylmethylene)bis(4-hydroxy-2H-chromen-2-ones)

Efficient synthesis of 3,3′-(arylmethylene)bis(4-hydroxy-2H-chromen-2-ones) has been achieved by methanesulfonic acid-catalyzed, microwave-assisted reaction of 4-hydroxycoumarin and aromatic aldehydes in ethanol. The procedure has the advantages of high yield, short reaction time, low energy consumption, and convenient work-up. Compound structures were confirmed by IR, ¹H NMR, and ¹³C NMR spectroscopy and by elemental analysis.     

Regioselective C-alkylation of alkyl 4-hydroxy-2-methylthiophene-3-carboxylates with α-halo ketones

Regioselective C- or O-alkylation of alkyl 4-hydroxy-2-methylthiophene-3-carboxylates with -halo ketones is possible, depending on the solvent nature. A convenient preparative method of C-alkylation was proposed and previously not easily accessible -hydroxythiophene derivatives were synthesized.     

Synthetic strategies to 2′-hydroxy-4′-methylsulfonylacetophenone,a key compound for the preparation of flavonoid derivatives

Different strategies for the synthesis of 2′-hydroxy-4′-methylsulfonylacetophenone are reported in the present paper. This compound is considered as a key synthon for the synthesis of new flavonoid derivatives designed as potential cyclooxygenase-2 inhibitors. The retrosynthetic approach via 3′-methylsulfonylacetophenone, which included three synthetic pathways, did not allow us to obtain the expected compound. However, a synthesis from 3-mercaptophenol led to the desired acetophenone in three steps: thiophenol methylation, Friedel–Crafts acetylation and oxidation of the sulphide to the corresponding sulfone. The desired compound, 2′-hydroxy-4′-methylsulfonylacetophenone, will be used as a synthon for the preparation of novel flavonoid derivatives, such as 2′-hydroxychalcones, flavanones, flavones, and flavonols.     

Chemoenzymatic synthesis of (4S,5R)-5-hydroxy-γ-decalactone

Reduction of ethyl 2-hydroxy-3-oxooctanoate with immobilised baker's yeast at pH 4.0 yields anti-2R,3R-dihydroxy ester with high diastereoselectivity and enantioselectivity (de 70%, ee 80%) which is conveniently converted to (4S,5R)-5-hydroxy-γ-decalactone.     

An Efficient Preparation of 4, 4′-Dicarboxy-2, 2′-Bipyridine

A convenient and high yield preparation of 4, 4′-dicarboxy-2, 2′-bipyridine from the oxidation 4, 4′-dimethyl-2, 2′-bipyridine with potassium dichromate in sulfuric acid is reported.     

Microwave Assisted Synthesis of 3,3',3″,3'″-o-,p-Phenylenedi-methylidinetetrakis-(4-hydroxy-2H-1-benzopyran-2-one)

Under microwave irradiation,2,2'-alkoxy-bridging or 4,4'-alkoxy-bridging dibenzaldehydes reacted with 4-hydroxycoumarin in DMF to give a series of 3,3',3″,3'″-o-and 3,3',3″,3'″-p-phenylenedimethylidinetetrakis-(4-hydroxy-2H-1-benzopyran-2-ones) in moderate yields.The structures of the synthetic coumarin derivatives were characterized with IR,1H NMR and MS spectroscopy as well as X-ray single crystallography.     

Synthesis and Insecticidal Activity of New 4-Hydroxy-2H-1-benzopyran-2-one Derivatives

Several stable and storable anticoagulant rodenticides involving both merits of acute and chronic rodenticides have been synthesized (Holbrook et al. in Arch Intern Med 165:1095–1106, 2005; Baglin et al. in Br J Haematol 132:277–285, 2006). The structures of synthesized compounds were confirmed by IR, ¹H NMR. The compounds were also evaluated for their anticoagulant and acute biologic activity (Lipton et al., JAMA 252:3004–3005, 3).     

Speciation of phytate ion in aqueous solution. Cadmium(II) interactions in aqueous NaCl at different ionic strengths

Interactions between myo-inositol 1,2,3,4,5,6-hexakis(dihydrogen phosphate) (phytic acid) and cadmium(II) were studied by using potentiometry (at 25 °C with the ISE-H⁺ glass electrode) in different metal to ligand (Phy) ratios (1:1≤Cd²⁺:Phy≤4:1) in NaCl_aq at different ionic strengths (0.1≤I/mol L⁻¹≤1). Nine Cd_iH_jPhy^{(12−2i−j)−} species are formed with i=1 and 2 and 4≤j≤7; and trinuclear Cd₃H₄Phy²⁻. Dependence of complex formation constants on ionic strength was modeled by using Specific ion Interaction Theory (SIT) equations. Phytate and cadmium speciation are also dependent on the metal to ligand ratio. Stability of Cd_iH_jPhy^{(12−2i−j)−} species was modeled as a function of both the ligand protonation step (j) and the number of metal cations bound to phytate (i), and relationships found were used for the prediction of species other than those experimentally determined (mainly di- and tri-protonated complexes), allowing the possibility of modeling Phy and Cd(II) behavior in natural waters and biological fluids. A critical evaluation of phytate sequestering ability toward cadmium(II) has been made under several experimental conditions, and the determination of an empirical parameter has been proposed for an objective “quantification” of this ability. A thorough analysis of literature data on phytate–cadmium(II) complexes has been performed. Previous contributions to this series: [1–8]     

The complementarity principle in chemical reactions. modifications of the indolinedione-indole rearrangement and enamine synthesis

The experimental discovery of a significant modification of a chemical reaction has always been considered a noteworthy achievement. As shown below, four modifications of the indolinedione-indole rearrangement and three modifications of the synthesis of β-diketones provide evidence for the usefulness of the complementarity principle [1] for the discovery of such specific reactions.     

The architecture and the Jones polynomial of polyhedral links

In this paper, we first recall some known architectures of polyhedral links (Qiu and Zhai in J Mol Struct (THEOCHEM) 756:163–166, 2005; Yang and Qiu in MATCH Commun Math Comput Chem 58:635–646, 2007; Qiu et al. in Sci China Ser B Chem 51:13–18, 2008; Hu et al. in J Math Chem 46:592–603, 2009; Cheng et al. in MATCH Commun Math Comput Chem 62:115–130, 2009; Cheng et al. in MATCH Commun Math Comput Chem 63:115–130, 2010; Liu et al. in J Math Chem 48:439–456 2010). Motivated by these architectures we introduce the notions of polyhedral links based on edge covering, vertex covering, and mixed edge and vertex covering, which include all polyhedral links in Qiu and Zhai (J Mol Struct (THEOCHEM) 756:163–166, 2005), Yang and Qiu (MATCH Commun Math Comput Chem 58:635–646, 2007), Qiu et al. (Sci China Ser B Chem 51:13–18, 2008), Hu et al. (J Math Chem 46:592–603, 2009), Cheng et al. (MATCH Commun Math Comput Chem 62:115–130, 2009), Cheng et al. (MATCH Commun Math Comput Chem 63:115–130, 2010), Liu et al. (J Math Chem 48:439–456, 2010) as special cases. The analysis of chirality of polyhedral links is very important in stereochemistry and the Jones polynomial is powerful in differentiating the chirality (Flapan in When topology meets chemistry. Cambridge Univ. Press, Cambridge, 2000). Then we give a detailed account of a result on the computation of the Jones polynomial of polyhedral links based on edge covering developed by Jin, Zhang, Dong and Tay (Electron. J. Comb. 17(1): R94, 2010) and, at the same time, by using this method we obtain some new computational results on polyhedral links of rational type and uniform polyhedral links with small edge covering units. These new computational results are helpful to judge the chirality of polyhedral links based on edge covering. Finally, we give some remarks and pose some problems for further study.     

Mesophilic Digestion Kinetics of Manure Slurry

Anaerobic digestion kinetics study of cow manure was performed at 35°C in bench-scale gas-lift digesters (3.78 l working volume) at eight different volatile solids (VS) loading rates in the range of 1.11–5.87 g l⁻¹ day⁻¹. The digesters produced methane at the rates of 0.44–1.18 l l⁻¹ day⁻¹, and the methane content of the biogas was found to increase with longer hydraulic retention time (HRT). Based on the experimental observations, the ultimate methane yield and the specific methane productivity were estimated to be 0.42 l CH₄ (g VS loaded)^–1 and 0.45 l CH₄ (g VS consumed)^–1, respectively. Total and dissolved chemical oxygen demand (COD) consumptions were calculated to be 59–17% and 78–43% at 24.4–4.6 days HRTs, respectively. Maximum concentration of volatile fatty acids in the effluent was observed as 0.7 g l^–1 at 4.6 days HRT, while it was below detection limit at HRTs longer than 11 days. The observed methane production rate did not compare well with the predictions of Chen and Hashimoto’s [1] and Hill’s [2] models using their recommended kinetic parameters. However, under the studied experimental conditions, the predictions of Chen and Hashimoto’s [1] model compared better to the observed data than that of Hill’s [2] model. The nonlinear regression analysis of the experimental data was performed using a derived methane production rate model, for a completely mixed anaerobic digester, involving Contois kinetics [3] with endogenous decay. The best fit values for the maximum specific growth rate (μ _m) and dimensionless kinetic parameter (K) were estimated as 0.43 day^–1 and 0.89, respectively. The experimental data were found to be within 95% confidence interval of the prediction of the derived methane production rate model with the sum of residual squared error as 0.02.     

Determination of Testosterone Metabolites in Rat Hepatocytes with and without Cryopreservation by On-Line SPE Column-Switching LC and MS Detection

In a recently published paper development of a sensitive automated “on-line” solid-phase extraction (SPE)/RP-HPLC assay for 6β-hydroxytestosterone (6β-OHT) with corticosterone as the internal standard (IS) was reported and its potential for quantification of various testosterone metabolites in culture media reflecting metabolic activity of cultured human and animal hepatocytes demonstrated [1]. In this following contribution the technique has been extended to determination of another five testosterone metabolites in cultured rat hepatocytes using an identical “on-line” SPE/RP-HPLC procedure and detection by tandem MS-MS with an atmospheric pressure chemical ionization (APCI) source in the selected reaction monitoring (SRM) mode as that described in [1]. All six testosterone metabolites, namely 2α-OHT, 2β-OHT, 6α-OHT, 6β-OHT, 7α-OHT and 16α-OHT, could be sufficiently separated from each other and thus an unequivocal assignment to the individual structures was achieved. Validation data are presented specifying the limits of quantitation as well as the mean values of the coefficients of variation (CV) for the target analytes and the accuracy obtained at five different days. Regio- and stereoselective testosterone hydroxylation by rat hepatocytes was measured in a long-term culture system with and without exposure to rifampicin as an inducer of liver CYP 3A4 activity. In addition, testosterone hydroxylation was analyzed in cultures of cryopreserved hepatocytes that had been stored at −196 °C. The rat hepatocytes were cultured after thawing for up to 11 days and induction of testosterone hydroxylase activity could be demonstrated in cultures which underwent a new cryopreservation protocol. This paper is dedicated to Professor Hinrich Cramer on the occasion of his 75th birthday.     

Characterization of unstable enzyme systems which evolve according to a three-exponential equation

The time course of an enzyme catalyzed reaction is normally followed either by monitoring the instantaneous concentration or velocity of an enzyme species or a product. In many enzyme catalyzed reactions these time variations are multi-exponential. The accurate fit of the relevant curves to obtain the kinetic parameters involved can be difficult using conventional methods (Galvez et al. in J Theor Biol 89:37–44, 1981; Garcia-Canovas et al. in Biochim Biophys Acta 912:417–423, 1987; Tudela et al. in Biochim Biophys Acta 912:408–416, 1987; Teruel et al. in Biochim Biophys Acta 911:256–260, 1987; Garrido del Solo et al. in Biochem J 294:459–464, 1993; Varon et al. in Int J Biochem 25:1889–1895, 1993; Garrido del Solo et al. in An Quim 89:319–324, 1993; Varon et al. in J Mol Catal 83:273–285, 1993; Garrido del Solo et al. in Biochem J 303(Pt 2):435–440, 1994; Garrido del Solo and Varon in An Quim 91:13–18, 1995; Garrido del Solo et al. in Biosystems 38:75–86, 1996; Garrido del Solo et al. in Int J Biochem Cell Biol 28:1371–1379, 1996; Garrido del Solo et al. in Int J Biochem Cell Biol 30:735–743, 1998; Varon et al. in J Mol Catal 59:97–118, 1990). In order to circumvent such difficulties Arribas et al. (J Math Chem 44:379–404, 2008) proposed an evaluation method which is applicable regardless of the complexity of the kinetic equation. This procedure is based on the numerical determination of statistical moments from experimental time progress curves. The fitting of these experimentally obtained moments to the corresponding theoretical symbolic expressions allows, in most cases, all the individual rate constants involved to be evaluated. In this paper we perform a general analysis that can be applied to any unstable enzyme system described by a three-exponential equation and apply it to a substrates induced enzyme inactivation process that is described by this type of equation. To verify the goodness of the method we have simulated time progress curves and applied the suggested procedure to these curves, obtaining kinetic parameters values very close to those used to obtain simulated curves. Finally, we compare our results with those obtained in previous contributions in which other procedures were used.     

<Emphasis Type="Italic">Ab initio</Emphasis> spectroscopic studies of non-rigid molecules: an application to acetic acid

The torsional levels of various isotopologues of acetic acid are determined from an ab initio potential energy surface using a flexible model depending on the OH-torsion and the methyl-torsion coordinates. Previous calculations for CH₃–COOH and CH₃–COOD are review and first theoretical energies of the one-deuterated species CH₂D–COOH are provided. The zero point vibrational energy correction and an exact definition for the methyl-torsional coordinate have been considered. The levels are compared with previous calculations (Senent in Mol Phys 99:1311, 2001) and experimental data (Havey et al. in J Mol Spectrosc 229:151, 2005). Isotopic effects on the torsional barriers and energies are discussed. For CH₂D–COOD, the deuteration splits by 25 cm⁻¹ the zero vibrational energy level.     

4-Hydroxy-2-quinolones. 152*. 3-acetyl-4-hydroxy-2-oxo-1,2-dihydroquinoline and its biologically active derivatives

A synthesis and study of the spatial structure of 3-acetyl-4-hydroxy-2-oxo-1,2-dihydroquinoline have been carried. 1-R-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids [1-(4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)ethylidene]hydrazides were prepared from this compound by two routes. A comparative analysis of the antitubercular properties of the synthesized compounds and of the closely structurally related N,N′-di(1-R-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carbonyl)hydrazines has been performed. *For Communication 151 see [1]. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 214–222, February, 2009.