New diarylheptanoids from Alnus japonica and their antioxidative activity

In the course of research on the bioactive constituents of woody plants in the Cyugoku area of Japan, a methanol extract of the leaves of Alnus japonica were found to have strong antioxidative activity. Ethyl acetate soluble and n-buthanol soluble fractions of the methanol extract had a potent antioxidative effect. Both fractions were purified by silica gel column chromatography and HPLC using an ODS column to give four new diarylheptanoids along with known diarylheptanoids and flavonoids. These new compounds were elucidated to be 7-(3,4-dihydroxyphenyl)-5-hydroxy-1-(4-hydroxyphenyl)-3-heptanone-5-O-beta-D-xylopyranoside (1), 1-(3,4-dihydroxyphenyl)-5-hydroxy-7-(4-hydroxyphenyl)-3-heptanone-5-O-beta-D-xylopyranoside (2), 1,7-bis-(3,4-dihydroxyphenyl)-5-hydroxy-3-heptanone-5-O-[2-(2-methylbutenoyl)]-beta-D-xylopyranoside (3) and 1,7-bis-(3,4-dihydroxyphenyl)-5-methoxy-3-heptanone (4) using spectral methods and especially 1H-, 13C-NMR and 2D-NMR measurements. The isolated compounds including their main constituent, oregonin (5), were tested for antioxidative activity. Some of these compounds having two catechol structures showed potent antioxidative activity. Compounds having one catechol structure showed moderate antioxidative activity, but a peracetate of 5 having no catechol structure exhibited no antioxidative activity. Thus the catechol structure of the diarylheptanoids is indispensable for antioxidative activity.     

Synthesis and antimicrobial activities of 4-aryl-3,4-dihydrocoumarins and 4-arylcoumarins

A new series of 4-aryl-3,4-dihydrocoumarins and 4-arylcoumarins were synthesized by the reaction of substituted cinnamic acids and 3-arylpropiolic acid with the corresponding phenols. These compounds were evaluated for antibacterial activity in vitro. The synthesized compounds displayed different degrees of antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Bacillus dysenteriae, and Candida albicans (a fungus). Compounds with catechol moieties and 7,8-substituted dihydroxyls in the A ring were the most active antimicrobial agents.     

Determination of some catechol derivatives by a flow injection electrochemiluminescent inhibition method

A flow injection electrochemiluminescent inhibition method has been developed for the determination of some catechol derivatives based on studying the inhibition phenomena of these compounds to the electrochemiluminescence of luminol. The linear calibration range of 5x10(-8) to 1x10(-5), 5x10(-8) to 1x10(-5) and 1x10(-8) to 5x10(-5) mol l(-1(,)) the detection limit of 1.2x10(-8), 2.1x10(-8) and 5.2x10(-9) mol l(-1)were obtained for catechol, 3,4-dihydroxybenzoic acid and chlorogenic acid, respectively. The method has higher sensitivity and wider dynamic range than conventional spectrophotometric method or chemiluminescent method. The method has been successfully applied to determine chlorogenic acid in cigarettes. The mechanism of the inhibition effect was proposed. Catechol derivatives mostly react with the freshly electrogenerated oxygen species on the electrode surface and lead to the inhibition of electrochemiluminescence.     

Effect of Substituents in Mussel-inspired Surface Primers on their Oxidation and Priming Efficiency

Marine mussels contain an abundant catechol moiety, 3,4-dihydroxyphenylalanine (DOPA), in their interfacial foot proteins. DOPA contributes to both surface adhesion and bridging between the surface and overhead proteins (surface priming) by taking advantage of the unique redox properties of catechol. Inspired by the mussel surface priming mechanism, herein we synthesized a series of DOPA-mimetic analogs – a bifunctional group molecule, consisting of a catechol group and an acrylic group at the opposite ends. The surface primers with differently substituted (−COOH, −CH₃) alkyl chains in the middle spacer were synthesized. Time-dependent oxidation and redox potentials of the surface primers were studied in an oxidizing environment to gain a better understanding of the mussel‘s redox chemistry. The thickness and degree of priming of the surface primers on silicon-based substrates were analyzed by ellipsometry and UV/Vis absorption spectroscopy. The post-reactivity of the acrylic groups of the primed layer was first visualized through a reaction with an acrylic group-reactive dye.     

The preparation and evaluation of 1-substituted 1,2,3,4-tetrahydro- and 3,4-dihydro-beta-carboline derivatives as potential antitumor agents

A series of 1-substituted 1,2,3,4-tetrahydro- and 3,4-dihydro-beta-carboline derivatives have been synthesized and evaluated for antitumor activity against murine P-388 and human tumor cell lines, KB-16, A-549 and HT-29. All of the compounds prepared, except for 19, showed significant cytotoxicity. Among them, compound 29 exhibited the most potent activity against all tested tumor cell lines. There was an apparent lack of correlation regarding cytotoxicity between 1,2,3,4-tetrahydro- and 3,4-dihydro-beta-carbolines. This study is the first to discover compound 29 as a potential lead for the development of future anticancer agents. The mode of inhibition for compound 29 was proposed.     

3-取代苄基-6-三氟甲基嘧啶-2,4(1H,3H)-二酮衍生物的合成及其除草活性的研究

为了进一步研究3-取代苄基-6-三氟甲基嘧啶-2,4(1H,3H)-二酮衍生物的除草活性, 以期发现更高活性化合物, 合成了16个未见文献报道的3-取代苄基-6-三氟甲基嘧啶-2,4(1H,3H)-二酮衍生物, 其结构均经过¹H NMR, IR和元素分析确证. 生测结果表明, 嘧啶环1-位取代基的变化, 不仅影响化合物的抑制活性与选择性, 可能还改变了化合物的作用方式. 定量的结构与活性关系研究表明, 当作用对象为油菜时, 化合物的活性可能主要与取代基R的摩尔分子折射常数有关; 当作用对象为稗草时, 化合物的活性可能主要与取代基R的电性参数有关. 1-位为氢时, 有利于对油菜生长的抑制; 1-位为甲基时, 有利于对稗草生长的抑制.     

Structure-based design, synthesis, and in vitro evaluation of bisubstrate inhibitors for catechol O-methyltransferase (COMT)

The enzyme catechol O-methyltransferase (COMT) catalyzes the Me group transfer from the cofactor S-adenosylmethionine (SAM) to the hydroxy group of catechol substrates. Potential bisubstrate inhibitors of COMT were developed by structure-based design and synthesized. The compounds were tested for in vitro inhibitory activity against COMT obtained from rat liver, and the inhibition kinetics were examined with regard to the binding sites of cofactor and substrate. One of the designed molecules was found to be a bisubstrate inhibitor of COMT with an IC50 = 2 microM. It exhibits competitive kinetics for the SAM and noncompetitive kinetics for the catechol binding site. Useful structure-activity relationships were established which provide important guidelines for the design of future generations of bisubstrate inhibitors of COMT.     

Iron(III) complexes with a tripodal N3O ligand containing an internal base as a model for catechol intradiol-cleaving dioxygenases

A bis(mu-alkoxo)-bridged dinuclear iron(III) complex [Fe(L)(NO3)]2(NO3)2 [1; HL = N,N-bis(2-pyridylmethyl)-N-(2-hydroxyethyl)amine] of the tripodal N3O ligand was prepared as a biomimetic model for the intradiol-cleaving dioxygenase enzymes. The reaction of 1 and catechol in the presence of excess triethylamine gave the catecholate (CAT) chelate bis(mu-alkoxo)-bridged dinuclear iron(III) complex [Fe(L)(CAT)]2 (2). The molecular structures of complexes 1 and 2 were determined by X-ray crystallography. Diiron complexes 1 and 2 contain the same bis(mu-alkoxo)diiron diamond core. All heteroatoms (N3O) of the ligand are coordinated to the iron center in complex 1 with two pyridine nitrogen atoms on the axial bonds, while one of the pyridyl arms of the ligand is left uncoordinated in complex 2. The interaction of the diiron complex 1 and 3,5-di-tert-butylcatechol (H2DBC) was investigated by electronic and mass spectroscopy. Complex 1 displays the intradiol-cleaving dioxygenase activity, and the coordinate ethoxyl arm of the ligand is capable of accepting the proton from catechol, which mimics the function of Tyr447 in the protocatechuate 3,4-dioxygenase as an internal base. The spectrophotometric titration experiment indicates the relatively low demand of the external base (0.8 equiv based on Fe(3+)) for attaining the highest dioxygenase activity of complex 1. The reaction rate of the reactive intermediate [Fe(HL)(DBC)]+ with dioxygen is 0.38 M(-1) s(-1) determined by kinetic studies.     

Synthesis of non-proteinogenic amino acids using Michael addition to unsaturated orthopyroglutamate derivative

Stereoselective synthesis of non-proteinogenic amino acids via Michael addition to 3,4-didehydropyroglutamate derivative in which the carboxyl function is protected as a 2,7,8-trioxabicyclo[3.2.1]octane (ABO ester) group is described. The obtained 3-substituted pyroglutamic ABO ester was directly converted to 3-substituted glutamic acids such as chlorpheg by acidic hydrolysis, whereas 3-substituted proline derivatives were obtained by chemoselective reduction of the lactam carbonyl group. A formal total synthesis of baclofen, a γ-aminobutyric acid (GABA) analogue, is also described.     

Effect of ultraviolet irradiation on the antitumor activity of bleomycin.

The effect of bleomycin (BLM) on the growth of the tumor, murine B16 melanoma, implanted onto the chorioallantoic membrane of chick embryo was examined. The inhibition ratio of BLM was about 30% at 3 micrograms/egg. This inhibitory effect of BLM on the growth of the tumor was enhanced by an appropriate dose of ultraviolet (UV) irradiation. The inhibition ratios of BLM irradiated for 10, 30 and 60 min were in order of about 50, 30 and 30% at 3 micrograms/egg. However, when these BLMs pretreated with 1 mM 1,2-benzenediol (catechol) were administrated, the inhibition ratios of BLM irradiated for 0, 10, 30 and 60 min were about 30, 20, 10 and 10%, respectively. On the other hand, the direct cytotoxicity of BLM to cultured murine B16 melanoma cells was depressed with UV irradiation and its toxic activity was further decreased by treatment with catechol after irradiation. These findings show that, although the antitumor activity of BLM is enhanced by UV irradiation, the activity of UV-irradiated BLM is inhibited by catechol. Moreover, it seems to show that the present results may provide a useful manner for the in vivo activation of BLM.     

Synthesis of 3-substituted 7-(3,3-dimethyl-1-triazeno)-10-methylphenothiazines as potential antitumor agents

A series of 3-substituted (chloro, bromo, fluoro or methyl) 7-(3,3-dimethyl-1-triazeno)-10-methylphenothiazines were synthesized as potential antitumor agents. Treatment of p-substituted anilines with ammonium thiocyanate in the presence of bromine gave 6-substituted 2-aminobenzthiazoles which, after methylation with methyl iodide were hydrolyzed in 50% potassium hydroxide to give 5-substituted 2-methylaminothiophenols in moderate yield. Condensation of methylaminothiophenols with 3,4-dichloronitrobenzene in ethanol under an atomsphere of nitrogen gave adducts which were cyclized in dimethylformamide under the catalysis of copper and cuprous iodide to give 3-substituted 7-nitro-10-methylphenothiazines. The nitro group was reduced to the amino function with stannous chloride. Diazotization of the amines followed by coupling with dimethylamine gave the corresponding triazenes.     

Potentiometric and spectroscopic studies on aluminium(III) complexes of some catechol derivatives

The interactions of aluminium(III) ion with the triprotic catechol derivatives (H3L), 2,3-dihydroxybenzoic acid (2,3-DHBA), 3,4-dihydroxyphenylacetic acid (3,4-DHPA), 3,4-dihydroxybenzoic acid (3,4-DHBA), and 3,4-dihydroxyhydrocinnamic acid (3,4-DHHCA) were investigated in aqueous solution at 25.0 degrees C. The Calvin-Bjerrum titration method was adopted for the determination of formation constants of proton-ligand and aluminium(III)-ligand complexes. Potentiometric and spectroscopic results indicated that these catechol derivatives exhibit a true bidentate character. The chelation occurs via their catecholate sites, with the exception of 2,3-DHBA. In the case of 2,3-DHBA complexes, the dominant species are either the salicylate type (COO-, O-) or catecholate type (O-, O-) complex. The protonation constants of ligands and their formation constants of Al(III) complexes were also correlated. The order of decreasing stabilities of complexes is: 3,4-DHPA>3,4-DHBA>3,4-DHHCA>2,3-DHBA.     

Synthesis of some novel 5-substituted benzamido-6-arylamino-pyrazolo[3,4-D]pyrimidin-4-one derivatives for herbicidal activity

Abstract

Sixteen novel 3-methylthio-5-substituted benzamido-6-arylamino-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4 (5H)-one derivatives (4a–p) were successfully synthesized from iminophosphoranes, aryl isocyanate, and substituted benzoylhydrazine. The structures of the title compounds were elucidated by FT-IR, ¹H NMR, ¹³C NMR, and HRMS. Herbicidal activity of the compounds 4a–p against Brassica napus (rape), Echinochloa crusgalli (barnyard grass), Cucumis sativus (cucumber), and Triticum aestivum (wheat) were determined. The results showed that 5-(2-chlorobenzamido)-6-phenylamino-3-methylthio-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4 (5H)-one (4c) displayed remarkable inhibition activity against the stalk and root of rape with 100% inhibition rate at the dosages of 10?mg/L and 100?mg/L, and 5-(4-nitrobenzamido)-6-phenylamino-3-methylthio-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4 (5H) -one (4d) exhibited excellent activity against the stalk and root of barnyard grass with 100% inhibition rate at the same dosages.     

2-氨基-1,3,4-噻二唑的抗水稻白叶枯病机制的探讨

药师寺国人等于1971年发现2-氨基-1,3,4-噻二唑(ATDA)具有优越的抗水稻白叶枯病菌的性能,并发现这种性能可被烟酰胺抵消.一般认为,ATDA的作用与细菌细胞中烟酰胺的代谢有关.为了探明ATDA的活性与结构的关系,并从中找出有效的同类化合物,进一步了解这个药剂的抗病机制,我们合成了几类新的噻二唑化合物,连同以前报导的     

取代邻苯二酚Mannich反应研究I:

把3-[N,N-双(羧甲基)氨甲基]邻苯二酚和哌啶,吡咯,二乙胺,吗啉和哌嗪在加热可得到相应的5-取位Mannich碱.研究了Mannich反应的机理,理解了这一Mannich反应的定位是由于反应物的分子内氢键.但是在与亚胺基二乙酸反应时或3-吗啉甲基邻苯二酚与吗啉反应,得到正常的6-取代Mannich碱.     

Potentiometric studies on the complexation of copper(II) by phenolic acids as discrete ligand models of humic substances

Studies on the complexation of copper(II) by phenolic acids, as ligand models of humic substances were done by potentiometry. The acids under study were: 3,4-dihydroxyhydrocinnamic acid or hydrocaffeic acid (1), 3,4-dihydroxyphenylacetic acid (2) and 3,4-dihydroxybenzoic acid or protocatechuic acid (3). Acidity constants of the ligands and the formation constants of metal-ligand complexes were evaluated by computer programs. The carboxylic group of the phenolic acids has different pK_a1 values, being the dissociation constants intrinsically related with the distance between the function and the aromatic nucleus. The results obtained allow concluding that acidity constants of the catechol moiety of the compounds are similar with pK_a2 and pK_a3 values between 9.47-9.41 and 11.55-11.70. The complexation properties of the three ligands towards copper(II) ion are quite similar, being the species found not different either in nature or stability. Although the model ligands have some structural differences no significant differences were found in their complexation properties towards copper(II). So, it can be postulated that complexation process is intrinsically related with the presence of a catechol group.     

Addition of Nitrile Oxides to Allyl Esters of Aryl(hetaryl)carboxylic Acids

3,5-Disubstituted isoxazolines with an aryl(hetaryl)carboxymethyl group in position 5 have been synthesized. The addition reaction of nitrile oxides to allyl esters of aryl(hetaryl) carboxylic acids occurs regiospecifically with the formation of the 5-substituted isomer. Initial pharmacological screening showed that 5-(4-bromobenzoyloxy)methyl-3-(3,4-dimethoxyphenyl)isoxazoline possesses marked nootropic activity.     

Substituent Effects on Reduction Potentials of Meta-substituted and Para-substituted Benzylideneanilines

Effects of meta-substituent of 3,4'/4,3'/3,3'-substituted benzylideneanilines (XBAYs) on the electrochemical reduction potentials (E_(Red)) were investigated, in which 49 samples of target compounds were synthesized, and their reduction potentials were measured by cyclic voltammetry. The substituent effects on the E_(Red) of target compounds were analyzed and an optimality equation with four parameters (Hammett constant σ of X, Hammett constant σ of Y, excited-state substituent constant σ_CC^ex of X, and the substituent specific cross-interaction effect Δσ_CC^ex2 between X and Y) was obtained. The results show that the factors affecting the E_(Red) of 3,4'/4,3'/3,3'-substituted XBAYs are different from those of 4,4'-substituted XBAYs. For 3,4'/4,3'/3,3'-substituted XBAYs, σ(X) and σ(Y) must be employed, and the contribution of Δσ_CC^ex2 is important and not negligible. Compared with 4,4'-substituted XBAYs, X group contributes less to 3,4'/4,3'/3,3'-substituted XBAYs, while Y group contributes more to them. Additionally, it was observed that either para-substituted XBAYs or meta-substituted XBAYs, the substituent effects of X are larger than those of Y on the E_(Red) of substituted XBAYs.     

Highly regioselective synthesis of 3,4-disubstituted 1H-pyrrole

A highly regioselective method for the synthesis of 3, 4-disubstituted 1H-pyrroles has been developed employing the ipso-directing property of a trimethylsilyl group. As a key starting material in this study, the known 3,4-bis(trimethylsilyl)-1H-pyrrole (3), was protected with carefully chosen groups, namely tert-butoxycarbonyl, N,N-dimethylaminosulfonyl, p-toluenesulfonyl, and triisopropylsilyl. A highly regioselective monoiodination of these 1-protected pyrroles was achieved by reaction with iodine-silver trifluoroacetate at low temperatures. Subsequent palladium-catalyzed cross-coupling reactions afforded 1-protected-4-substituted 3-trimethylsilyl-1H-pyrroles, which again underwent further room-temperature ipso-iodination and palladium-catalyzed cross-coupling reactions to provide symmetrical and unsymmetrical 1-protected-3,4-disubstituted 1H-pyrroles. Deprotection of 1-(tert-butoxycarbonyl) and 1-(N, N-dimethylaminosulfonyl) groups was found to be nontrivial. The 1-(p-toluenesulfonyl) protecting group was eventually proved to be superior to other protection groups, because it was readily removed after stepwise ipso monoiodinations and palladium-catalyzed cross-coupling reactions.