Use of Ultrasound and Microwave Irradiation for Clean and Efficient Synthesis of 3,3’-(Arylmethylene)bis (2-hydroxynaphthalene-1,4-dione) Derivatives

Nine 3,3’-(arylmethylene)bis(2-hydroxynaphthalene-1,4-dione) derivatives were synthesized through the reaction between 2-hydroxy-1,4-naphthalen-1,4-dione and different aromatic alde-hydes in water applying ultrasonic irradiation for 5 min at room temperature and microwave irradiation for 15 min at 70°;C. Two of the nine derivatives, compounds 3-e and 3-i, obtained from 3-bromo-hydroxybenzaldehyde and 5-methylfuran-2-carbaldehyde, respectively, are previously unpublished. The structures of all compounds were established on the basis of their spectral data and mass analysis. The attractive features of this synthesis protocol include mild conditions, high atom-economy and excellent yields with the elimination of water as the only by-product.

Determination of Trace Silver( Ⅰ ) in Basic Aqueous Solution by Electrochemiluminescence of a New Reagent 6-(2-Hydroxy-4-Diethylaminophenylazo)-2,3-Dihydro-1,4-Phthalazine-1,4-Dione

The electrochemiluminescence (ECL) of a new reagent 6- (2-hydroxy- 4 diethy laminophenylazo)-2,3-dihydro-1 ,4-phthalazine-1,4-dione (HDEA) in a basic aqueous so lution was studied by using the apparatus designed by ourselves. Trace amounts of silver ( Ⅰ ) shows a significant effect on the efficiency of light emission of HDEA during a positive trigonometrical wave pulse was exerted on the solution. The linear relationship between the light intensity and the concentration of silver( Ⅰ ) occurs in the range of 5. 0×10-8 to 3. 0×10-8 mol/L Ag(Ⅰ ) in a medium of KOH-KCl-HDEA (pH= 12. 8). The detection limit of the method is 2. 0×10-8 mol/LAg( Ⅰ ), and the r. s. d. for 1.0×10-7 mo)/L Ag ( Ⅰ ) is 5%. Of 21 metal ions concerned, only nickel( Ⅱ ), cerium( Ⅳ ) and cobalt( Ⅱ ) interfere the silver detection seriously; Ⅰ and Br also have some interference.

Synthesis and Herbicidal Activity of 1-Phenoxyacetyl-3-arylimidazolidine-2,4-dione Compounds

In order to find new herbicidal compounds, twelve novel 1-phenoxyacetyl-3-arylimidazolidine-2,4-dione compounds were designed and synthesized by substructure combination strategy using 3-arylimidazolidine-2,4-dione as the intermediate. The structures of the target compounds were confirmed by;H NMR and IR. The preliminary bioassay results showed that most of the target compounds had good inhibition against rape and barnyardgrass at the concentration of 100 mg/L. Especially, compound H3 and H5 showed 100% inhibitory activity against rape.

Novel Route for Synthesis of Thiozolidine-2,4-Dione Derivatives as a Mannich Base

The Mannich base of Thiozolidine-2,4-dione derivatives has come to lime light due to their various pharmacological activities. Thiazolidine-2,4-dione is an extensively explored heterocyclic nucleus for designing of novel agents implicated for a wide variety of pathophysiological conditions, that is, diabetes, diabetic complications, cancer, arthritis, inflammation, microbial infection, and melanoma. In present work, synthesis quinoline attached imidazoline derivative using (3 + 2) cyclo-addition via imine of quinoline and TosMIC. These derivatives were converted to Mannich bases of thiozolidine-2,4-dione using Knoevenagel condensation. The sulfonamide analogues of thiozolidine-2,4-Dione were also synthesized and characterized by using alkylation conditions.

Synthesis, Crystal Structure and Antitumor Activity of 2-(3-Methyl-5-(methylthio)-4H-1,2,4-triazol-4-yl)isoindoline-1,3-dione

The title compound 2-（3-methyl-5-（methylthio）-4H-1,2,4-triazol-4-yl）isoindoline- 1,3-dione （C12H10NaO2S, Mr= 274.30） has been synthesized by a three-step procedure including the cyclization, hydrazinolysis and substitution reactions, and its crystal structure was determined by X-ray single-crystal diffraction. The crystal belongs to the monoclinic system, space group P2/c with a = 12.264（3）, b = 14.646（3）, c = 14.349（4） A,β = 91.69（3）°,μ = 0.255 mm1, Mr = 274.30, V = 2576.2（10） A3, Z =8, Dc = 1.414 g/cm3, F（000） = 1136, R = 0.0487 and wR = 0.1329 for 4048 observed reflections with I 〉 2σ（I）. In addition, the preliminary bioassay suggested that the title compound 6 exhibits relatively good antitumor activity against HT-29 and MCF-7.

Synthesis,Crystal Structure and Cytotoxic Activities of 1-(Prop-2-yn-1-yl)-7,8-dihydro-1H-benzo[d][1,3]-thiazine-2,5(4H,6H)-dione Derivatives

The important synthetic precursor（Ⅲ）, 1-（prop-2-yn-1-yl）-7,8-dihydro-1Hbenzo[d][1,3]thiazine-2,5（4H,6H）-dione（C（11）H（11）NO2S）, was prepared through a three-component reaction, which was further transferred into cytotoxic triazoles by alkylation and ＂click＂ synthesis in satisfactory yields of 87%^95%. Their structures were characterized by IR, H-RESI-MS and NMR analysis. Meanwhile, the crystal of Ⅲ was obtained and determined by X-ray single-crystal diffraction. Crystal data： orthorhombic system, space group P212121, a = 5.189（4）, b = 8.661（6）, c = 23.498（17） A, V = 1056.2（13） A^3, Z = 4, F（000） = 464, Dc = 1.392 g/cm^3, μ =0.284 mm^-1, R = 0.0637 and wR = 0.1668 for 8182 independent reflections（R（int） = 0.1580） and 2166 observed ones（I 〉 2σ（I））.

Functional Ionic Liquids Promoted Double Michael Reaction of Benzofuran-3-one or 1-1ndone and Symmetric Dienones： Construction of Spiro[benzofuran-2,1′-cyclohexane]-3-one or Spiro[cyclohexane-1,2′-indene]-1′,4（3′H）-dione Derivatives

The double Michael reactions between benzofuran-3-one or 1-indone and symmetric dienones in the presence of catalytic ionic liquids were successfully developed and spiro[benzofuran-2, 1′-cyclohexane]-3-one or spiro[cyclo- hexane-1,2′-indene]-1′,4（3′H）-dione derivatives containing a spiro quaternary stereogenic center, which widely exist in biologically active products and building blocks in organic synthesis, were obtained in excellent yields （up to 99%）. This catalytic system was also extended to the double Michael reaction of less reactive 1-indone and the desired products were also obtained in 31%-62% yields. The catalytic system was highly active and efficient for a broad of substrates under mild conditions.

Synthesis of pyrazine-2,3-dicarbonitrile and 1,2,4-triazine-5(4H)-one derivatives from furan-2,3-diones

The reaction of furan-2,3-diones with S-methylisothiosemicarbazide hydroiodide yielded novel 1,2,4- triazine-5（4H）-ones, and reaction of furan-2,3-diones with diaminomaleonitrile led to the formation of pyrazine-2,3-dicarbonitrile derivatives, and the hydrolysis of these products led to the formation of more new pyrazine-2,3-dicarbonitrile derivatives. These compounds are potential herbicides and pesticides.

Improved microwave-assisted catalyst-free synthesis of9-aryl-5,9-dihydropyrimido[4,5-d][1,2,4]triazolo[1,5-a]pyrimidine-6,8(4H,7H)-dione derivatives

Agreen regioselective synthesis of some new and known 9-aryl-5,9-dihydropyrimido[4,5-d][l,2,4]triazolo[1,5-a]pyrimidine-6,8（4H,7H）-diones has been described via the microwave-assisted one-pot reaction of 3-amino-1H-1,2,4-triazoles,aromatic aldehydes and barbituric acids under solvent- and catalyst-free conditions.This operationally simple procedure is less laborious and provides a better scope than previously reported procedures.

DABCO Promoted an Efficient and Convenient Synthesis of Pyrrole in Aqueous Medium

The synthesis of C-substituted and N-substituted pyrrole is described by the reaction of phenacyl bromides, pentane-2, 4-dione and amine in aqueous medium using DABCO as a catalyst. The method is very convenient and applicable for alkyl as well as aryl amines and phenacyl bromides. The procedure is amenable for the synthesis of new substituted pyrroles. Moreover, aqueous medium makes the method more eco-friendly.

Determination of ergocalciferol in human plasma after Diels-Alder derivatization by LC-MS/MS and its application to a bioequivalence study

An accurate, sensitive and selective method is developed for determination of ergoealeiferol （vitamin D2） in human plasma using LC-MS/MS. After liquid-liquid extraction with n-hexane, ergoealeiferol was derivatized by reacting with 4-phenyl-l,2,4-triazoline-3,5-dione （PTAD）, a strong dienophile based on Diels-Alder reaction. Ergocalciferol and its deuterated internal standard, ergocalciferol-d6, were analyzed on X Select CSH Cls （100 mmx4.6 mm, 2.5 lam） column using acetonitrile and 0.1% （v/v） formic acid in water containing 0.14% methylamine within 6.0 min under gradient elution mode. Tandem mass spectrometry in positive ionization mode was used to quantify ergocalciferol by multiple reaction monitoring （MRM）. Entire data processing was done using Watson LIMSTM software which provided excellent data integrity and high throughput with improved operational efficiency. The major advantage of this method includes higher sensitivity （0.10 ng/mL）, superior extraction efficiency （〉83%） and small sample volume （100 ~tL） for processing. The method was linear in the concentration range of 0.10-100 ng/mL for ergoealciferol. The intra-batch and inter-batch accuracy and precision （% CV） values varied from 97.3% to 109.0% and 1.01% to 5.16%, respectively. The method was successfully applied to support a bioequivalence study of 1.25 mg ergoealciferol capsules in 12 healthy subjects.

Efficient production of 14α‑OH‑AD by engineered Mycolicibacterium neoaurum via coupled cofactor and reconstructed electron transport system

14α-hydroxy-androst-4-ene-3,17-dione(14α-OH-AD)is an important precursor for the synthesis of steroid drugs with anticancer and carcinolytic activity.Initially,14α-OH-AD was mostly synthesized by whole-cell fermentation of mold fungi using androstenedione(AD)as a substrate,which had difficulties in product isolation and purification as well as problems of high production cost.In this study,the source of the 14α-hydroxylase gene was expanded.And 14α-hydroxylase genes were heterologously expressed in Mycolicibacterium neoaurum(MNR)M3ΔksdD,which enabled the one-step biotransformation from the cheap substrate phytosterols(PS)to 14α-OH-AD,reducing the difficulty of product purification and production cost.What is more,to alleviate the problem of poor activity of 14α-hydroxylase,the 14α-hydroxylase gene was co-expressed with the electron transport chain element genes and the coenzyme regeneration genes,and a superior engineered strain MNR M3ΔksdD/pMV261-14α-G6PDH was obtained.Finally,the transformation conditions were optimized for the transformation of PS by the engineered strain.The molar yield of 14α-OH-AD reached to 60.4±2.3%(about 0.22 g/L productivity).This study investigated for the first time the effects of the tandem electron transport chain element genes and the tandem coenzyme regeneration genes on the 14α-hydroxylation reaction,providing a theoretical basis for the industrial production of 14α-OH-AD.

阳桃根中苯醌类化合物的分离鉴定与含量测定

目的：研究阳桃根（ACLR）中苯醌类化学成分的类型及含量测定方法。方法：利用色谱分离法、核磁共振技术对阳桃根药材60％乙醇提取物中的环己烷萃取部位进行分离、鉴定，并应用HPLC法对药材中的苯醌类化学成分进行含量测定。结果：分离得到2个苯醌类化合物：2-methoxy-6-nonyl-cyclohexa．2，5-diene-1，4-dione（MNDD）；2-dodecyl-6-methoxy-cyclohexa-2，5-diene-1，4-dione（DMDD）；MNDD，DMDD分别在0．177～2．657斗g和0．094～1．416μg进样量与峰面积有良好的线性关系；平均加样回收率为98．96％（RSD1．59％），99．55％（RSD0．98％）。结论：首次从植物中分离得到2个苯醌类化合物；HPLC测定方法简便、快速、稳定、准确可靠、重复性好，可用于阳桃根药材中MNDD，DMDD的质量控制。

A streamlined high throughput screening method for the Mycobacterium neoaurum mutants with expected yield of biotransformation derivatives from sterols

Steroidal drugs have wide indications such as anti-inflammation, anti-tumor, endocrine regulation,fertility management. Phytosterol is the main starting materials for the industrial synthesis of steroid drugs. Microbial transformation of phytosterol is a simple and environmentally friendly process. Efficient microbial strains for industrial phytosterol transformation are critical for the commercial success. To this end, a 96-well plate based method was developed to discriminate the mixture of 4-androstene-3,17-dione, androsta-1,4-diene-3,17-dione, and bisnoraldehyde, with different ratio of the 3 components in the mixture, which mimics the sterol bioconversion products by using the Mycobacterium neoaurum. The M. neoaurum bioconversed broth test using phytosterol as substrate also found that the spectrum methodology can evaluate the relative content of different compounds. The method is practical, high throughput and can replace the conventional HPLC-based assay for rapid selection of desired microbial strains.