Determination of Dufulin Residue in Vegetables, Rice, and Tobacco Using Liquid Chromatography with Tandem Mass Spectrometry.

A rapid and accurate LC/MS/MS method using positive electrospray ionization was established for the determination of residues of the novel plant antiviral agent dufulin in samples of tobacco leaf (dry), tomato, cucumber, and rice. Samples were extracted with acetonitrile; cleaned up by dispersive SPE using primary secondary amine, C18, and graphitized carbon black sorbents; separated on a C18 column; and confirmed by multiple reaction monitoring mode MS with a matrix effect of -21.5-19.6%. The method showed satisfactory linearity (R2≥0.9912) for the target compound. The LOD and the LOQ were 0.05 and 0.15 µg/kg, respectively. The mean recoveries from four matrixes varied from 71.9 to 93.6% with intraday RSD in the range of 2.9 to 9.0% and interday RSD 6.9 to 15.2%. The method was successfully applied for analysis of dufulin in actual trial samples.

Metal free catalytic hydroboration of multiple bonds in methanol using N-heterocyclic carbenes under open atmosphere.

An easy to operate method of catalytic hydroboration of unsaturated compounds has been developed with wide substrate scope. Reactions of various aldimines, ketimines, α,ß-unsaturated carbonyl compounds, and alkynes were successfully executed with bis(pinacolato)diboron and N-heterocyclic carbenes in methanol without requiring a transition metal or inert atmosphere.

Chiral cinchona alkaloid-derived thiourea catalyst for enantioselective synthesis of novel ß-amino esters by Mannich reaction.

A cinchona alkaloid-derived thiourea catalyst has been designed to access new asymmetric ß-amino esters bearing benzothiazole moiety by utilizing a Mannich reaction between an imine and a malonate. A simultaneous activation of the two imine functionalities and malonate by the bifunctional chiral organocatalyst is proposed to account for the good yields (71-91%) and high enantiomeric excess (89.4-98.5%) under mild conditions.

Analytical and semi-preparative HPLC enantioseparation of novel pyridazin-3(2H)-one derivatives with α-aminophosphonate moiety using immobilized polysaccharide chiral stationary phases.

The direct HPLC enantioseparation of a novel series of chiral pyridazin-3(2H)-one derivatives with α-aminophosphonate moiety was performed on two immobilized polysaccharide chiral stationary phases (Chiralpak IA, Chiralpak IC) using n-hexane (n-Hex)/dichloromethane (DCM) mobile phase with 5% alcohol additive. Good baseline separation of the enantiomers was achieved using amylose tris-(3,5-dimethylphenylcarbamate) chiral stationary phases (Chiralpak IA) on analytical scale. The analytical method was further scaled up to semi-preparative loading to obtain small amounts of both the enantiomers of pyridazin-3(2H)-one derivative. The semi-preparative resolution of all compounds was successfully achieved with n-hexane/dichloromethane/ethanol (EtOH) as mobile phase using a semi-preparative Chiralpak IA column. The first fractions were isolated with purities of >99.9% (enantiomeric excess (e.e.), and the second fractions were obtained with purities of >98.2% (enantiomeric excess). The assignment of the absolute configuration was established for the F1 fraction of compound a-2 by single-crystal X-ray diffraction method.

Antiviral activity and mechanism of action of novel thiourea containing chiral phosphonate on tobacco mosaic virus.

Using half-leaf method O,O'-diisopropyl (3-(L-1-(benzylamino)-1-oxo-3- phenylpropan-2-yl)thioureido)(phenyl)methyl phosphonate (2009104) was studied for its activity on tobacco mosaic virus (TMV). It showed good curative activity in vivo and the curative activity at 500 µg/mL was found to be 53.3%. In vivo treatment with the control agent Ningnanmycin at 500 µg/mL resulted in 51.2% inhibition and curative inhibition rates respectively. Dot-ELISA test was employed to verify the efficacy of activity of compound 200910 for anti-TMV activity. The mechanism of action of compound 2009104 to resist TMV was also studied. The results showed that the resistance enzymes PAL, POD, SOD activity and chlorophyll content after TMV inoculation K(326) (Nicotiana tabacum K(326)) of tobacco plants followed by treatment with compound 2009104 were significantly enhanced. The study of the effect of compound 2009104 on TMV capsid protein (CP) showed that it inhibited the polymerization process of TMV-CP in vitro.

Synthesis and molecular docking studies of novel 2-chloro-pyridine derivatives containing flavone moieties as potential antitumor agents.

A series of novel 2-chloro-pyridine derivatives containing flavone, chrome or dihydropyrazole moieties as potential telomerase inhibitors were synthesized. The bioassay tests showed that compounds 6e and 6f exhibited some effect against gastric cancer cell SGC-7901 with IC(50) values of 22.28+/-6.26 and 18.45+/-2.79 microg/mL, respectively. All title compounds were assayed for telomerase inhibition by a modified TRAP assay, the results showed that compound 6e can strongly inhibit telomerase with IC(50) value of 0.8+/-0.07 microM. Docking simulation was performed to position compound 6e into the active site of telomerase (3DU6) to determine the probable binding model.

Synthesis and antiviral activity of 5­(4­chlorophenyl)-1,3,4-thiadiazole sulfonamides.

Starting from 4-chlorobenzoic acid, 10 new 5-(4-chlorophenyl)-N-substituted-N-1,3,4-thiadiazole-2-sulfonamide derivatives were synthesized in six-steps. Esterification of 4-chlorobenzoic acid with methanol and subsequent hydrazination, salt formation and cyclization afforded 5-(4-chlorophen-yl)-1,3,4-thiadiazole-2-thiol (5). Conversion of this intermediate into sulfonyl chloride 6, followed by nucleophilic attack of the amines gave the title sulfonamides 7a-7j whose structures were confirmed by NMR, IR and elemental analysis. The bioassay tests showed that compounds 7b and 7i possessed certain anti-tobacco mosaic virus activity.

Asymmetric synthesis of alpha-aminophosphonates using the inexpensive chiral catalyst 1,1'-binaphthol phosphate.

Asymmetric addition under mild conditions of dialkyl phosphites on aldimines derived from cinnamaldehyde catalyzed by the inexpensive chiral organocatalyst (R)-3,3'-[4-fluorophenyl](2)-1,1'-binaphthol phosphate has been found effective to give new alpha-amino-phosphonates 9 in moderate yields (30-65%) and enantiomeric excess (8.4%-61.9%).

Synthesis, structure and antibacterial activity of new 2-(1-(2-(substituted-phenyl)-5-methyloxazol-4-yl)-3-(2-substitued-phenyl)-4,5-dihydro-1H-pyrazol-5-yl)-7-substitued-1,2,3,4-tetrahydroisoquinoline derivatives.

A series of new 2-(1-(2-(substituted-phenyl)-5-methyloxazol-4-yl)-3-(2-substitued-phenyl)-4,5-dihydro-1H-pyrazol-5-yl)-7-substitued-1,2,3,4-tetrahydroisoquinoline derivatives were synthesized. The results showed that compounds 9q and 10q can strongly inhibit Staphylococcus aureus DNA gyrase and Bacillus subtilis DNA gyrase (with IC(50s) of 0.125 and 0.25 microg/mL against S. aureus DNA gyrase, 0.25 and 0.125 microg/mL against B. subtilis DNA gyrase). On the basis of the biological results, structure-activity relationships were also discussed.

An effective route to fluorine containing asymmetric alpha-aminophosphonates using chiral Bronsted acid catalyst.

Asymmetric addition of dialkyl phosphites (--CH2CH3, --CH2CH2CH3, --CH(CH3)2, --CH2(CH2)3CH3, --CH2CH2OCH3 and --CH2CH2OC2H5) induced by chiral organocatalyst e.g. (R)- and (S)-3,3'-[3,5-bis(trifluoromethyl)phenyl]2-1,1'-binaphthyl phosphate on fluorinated aldimines derived from cinnamaldehyde has been found effective to give new bioactive alpha-aminophosphonates in good yields (58-73%) and high enantiomeric excess (64.6%-90.6%) under mild conditions.

Synthesis, structure and antibacterial activity of novel 1-(5-substituted-3-substituted-4,5-dihydropyrazol-1-yl)ethanone oxime ester derivatives.

A series of novel 1-(5-substituted-3-substituted-4,5-dihydropyrazol-1-yl)ethanone oxime ester derivatives are synthesized. The results show that compounds 14 and 26c can strongly inhibit Staphylococcus aureus DNA gyrase and Escherichia coli DNA gyrase (with IC(50) of 0.25 and 0.125 microg/mL against S. aureus DNA gyrase, 0.125 and 0.25 microg/mL against E. coli DNA gyrase). On the basis of the biological results, structure-activity relationships are also discussed.

Synthesis and antifungal activity of novel sulfoxide derivatives containing trimethoxyphenyl substituted 1,3,4-thiadiazole and 1,3,4-oxadiazole moiety.

Selective oxidation of sulfides 7 or 8 to sulfoxides 9 or 10 is achieved by mCPBA. The structures of the compounds 9 or 10 are confirmed by elemental analysis, IR, and (1)H NMR. The bioassay results showed that title compound 10a possess high antifungal activities with EC(50) values ranging from 19.91 to 63.97 microg/mL. The mechanism of action of 10a against Sclerotinia sclerotiorum was studied. After treating with compound 10a at 100 microg/mL for 12 h, the mycelial reducing sugar, D-GlcNAc, soluble protein and pyruvate content, chitinase activity showed declining tendency.

Synthesis and antiviral activity of novel pyrazole derivatives containing oxime esters group.

Fourteen title compounds, 1-substituted-5-substitutedphenylthio-4-pyrazolaldoxime ester derivatives 4a-4n, were synthesized from the starting material 1-substitutedphenyl-3-methyl-5-substitutedphenylthio-4-pyrazolaldoximes 3 by treatment with acyl chloride. The synthesized compounds were characterized by physical constants, and the structures of the title compounds were further confirmed by IR, 1H NMR, 13C NMR and elemental analysis. The bioassay results showed that title compounds possessed weak to good anti-TMV bioactivity with 4l showing significant enhancement of disease resistance in tobacco leaves with high affinity for TMV CP.

Synthesis and antiviral activities of novel chiral cyanoacrylate derivatives with (E) configuration.

The intermediate 3 is converted by the nucleophilic attack of the appropriate aryl (heterocyclic) amine under microwave irradiation into the chiral (E) isomers of title compound 4. These compounds exhibited weak to good anti-TMV bioactivity with (R)-4p showing significant enhancement of disease resistance in tobacco leaves.

Studies on the chemical constituents and anticancer activity of Saxifraga stolonifera (L) Meeb.

Saxifraga stolonifera, an evergreen dicotyledon, has been identified as an important resource in Chinese medicine due to its anticancer activity. In the present report, chemical components of S. stolonifera (L) Meeb which is found in Guizhou province were investigated. Ten compounds were isolated from ethanol extracts of S. stolonifera plant and were identified as n-C(31)H(64) (1), (n-C(17)H(35))(2)CO (2), beta-sitosterol (3), n-C(29)H(60) (4), Bergenin (5), Protocatechuic acid (6), Gallic acid (7), Quercitrin 3-O-alpha-l-rhamnoside (8), Quercetin (9), and Quercetin 3-O-beta-d-glucopyranoside (10). Among them, n-C(31)H(64) (1), (n-C(17)H(35))(2)CO (2), beta-sitosterol (3), and n-C(29)H(60) (4) were isolated from this plant for the first time. The anticancer activities of S. stolonifera constituents on human gastric carcinoma cell line BGC-823 were evaluated by MTT assay and microscopic observation, DNA fragmentation, and flow cytometry analysis assay. It was found that quercetin could inhibit cell viability after 72 h of exposure. Furthermore, DNA ladder assay revealed that quercetin could induce DNA strand break in a concentration- and time-dependent fashion. Flow cytometric analysis shows that quercetin can induce 11.82% BGC-823 cell apoptosis in 48 h. These data reveal that quercetin is a potential agent capable of inducing apoptosis in BGC-823 cells.

Analytical and semi-preparative enantioseparation of organic phosphonates on a new immobilized amylose based chiral stationary phase.

Two chiral stationary phases derived from derivatized amylose (Chiralpak AD-H and Chiralpak IA) have been used to separate the enantiomers of new diethyl benzamidoarylmethylphosphonates. The data obtained indicate that all the studied compounds could be easily baseline resolved on both columns. Owing to the different techniques involved in their preparation, the two stationary phases differ in their abilities to effect enantiomeric separation. The semi-preparative separation of all compounds was executed successfully in n-hexane/EtOH on the new immobilized Chiralpak IA column. The analytical assessment of the enantiomeric excess values of all collected fractions was higher than 97%. The stereochemical configuration for the F1 fraction of a diethyl benzamidoarylmethylphosphonate was determined by X-ray diffraction structure analysis.

Synthesis and antiviral activities of amide derivatives containing the alpha-aminophosphonate moiety.

Starting from (substituted-)benzaldehydes, the title compounds 6 were synthesized through five step reactions. Benzaldehydes were treated with ammonium hydroxide, followed by dialkyl phosphite, to give dialkyl N-(arylmethylene)-1-amino-1-aryl methylphosphonates ( 3). Phosphonates 3 were then easily hydrolyzed to give dialkyl 1-amino-1-aryl-methylphosphonates 5. Target compounds 6 were then obtained by the reaction of 5 and substituted benzoic or cinnamic acid. Their structures were clearly verified by spectroscopic data (IR, 1H, 13C, and 31P NMR, and elemental analysis). These compounds were shown to be antivirally active in the bioassay. It was found that title compounds 6g, 6l, and 6n had the same inactivation effect of TMV (EC 50 = 54.8, 60.0, and 65.2 microg/mL, respectively) as commercial product Ningnanmycin (EC50 = 55.6 microg/mL). To the best of our knowledge, this is the first report on the synthesis and antiviral activity of amide derivatives containing an alpha-aminophosphonate moiety.

Synthesis, antiviral and antifungal bioactivity of 2-cyano-acrylate derivatives containing phosphonyl moieties.

Alkyl 2-cyano-3-methylthio-3-phosphonylacrylates were synthesized by the reaction of alkyl 2-cyano-3,3-dimethylthioacrylates with dialkyl phosphites. The structures of the new compounds were characterized by elemental analyses, IR, 1H-, 13C- and 31P-NMR spectral data. These compounds were tested in vitro against pathogenic fungi, namely, Fusarium graminearum, Cytospora mandshurica and Fusarium oxysporum. Amongst all compounds, 2d and 2t were found to be effective against the tested fungi at 50 microg/mL. A half-leaf method was used to determine the in vivo protective, inactivation and curative efficacies of the title products against tobacco mosaic virus (TMV). Title compounds 2a and 2b were found to possess good in vivo curative, protection and inactivation effects against TMV with inhibitory rates at 500 mg/L of 60.0, 89.4 and 56.5 and 64.2, 84.2 and 61.2 %, respectively. To the best of our knowledge, this is the first report on the antiviral and antifungal activity of alkyl 2-cyano-3-methylthio-3-phosphonylacrylates.

Production and selected fuel properties of biodiesel from promising non-edible oils: Euphorbia lathyris L., Sapium sebiferum L. and Jatropha curcas L.

A comparative study on the composition, biodiesel production and fuel properties of non-edible oils from Euphorbia lathyris L. (EL), Sapium sebiferum L. (SS), and Jatropha curcas L. (JC) was conducted. Under optimal conditions, the FAME content and yield of the three oils were greater than 97.5 wt.% and 84.0%, respectively. The best biodiesel was produced from EL due to its high monounsaturation (82.66 wt.%, Cn: 1), low polyunsaturation (6.49 wt.%, Cn: 2, 3) and appropriate proportion of saturated components (8.78 wt.%, Cn: 0). Namely, EL biodiesel possessed a cetane number of 59.6, an oxidation stability of 10.4 h and a cold filter plug point of -11 °C. However, the cetane number (40.2) and oxidative stability (0.8 h) of dewaxed SS kernel oil (DSSK) biodiesel were low due to the high polyunsaturation (72.79 wt.%). In general, the results suggest that E. lathyris L. is a promising species for biodiesel feedstock.

Antiproliferation and cell apoptosis inducing bioactivities of constituents from Dysosma versipellis in PC3 and Bcap-37 cell lines.

BACKGROUND: Recently, interest in phytochemicals from traditional Chinese medicinal herbs with the capability to inhibit cancer cells growth and proliferation has been growing rapidly due to their nontoxic nature. Dysosma versipellis as Bereridaceae plants is an endemic species in China, which has been proved to be an important Chinese herbal medicine because of its biological activity. However, systematic and comprehensive studies on the phytochemicals from Dysosma versipellis and their bioactivity are limited. RESULTS: Fifteen compounds were isolated and characterized from the roots of Dysosma versipellis, among which six compounds were isolated from this plant for the first time. The inhibitory activities of these compounds were investigated on tumor cells PC3, Bcap-37 and BGC-823 in vitro by MTT method, and the results showed that podophyllotoxone (PTO) and 4'-demethyldeoxypodophyllotoxin (DDPT) had potent inhibitory activities against the growth of human carcinoma cell lines. Subsequent fluorescence staining and flow cytometry analysis indicated that these two compounds could induce apoptosis in PC3 and Bcap-37 cells, and the apoptosis ratios reached the peak (12.0% and 14.1%) after 72 h of treatment at 20 µM, respectively. CONCLUSIONS: This study suggests that most of the compounds from the roots of D. versipellis could inhibit the growth of human carcinoma cells. In addition, PTO and DDPT could induce apoptosis of tumor cells.