LC-MS/MS analysis of 2-aminothiazoline-4-carboxylic acid as a forensic biomarker for cyanide poisoning

AIM: To demonstrate the potential of using 2-aminothiazoline-4-carboxylic acid(ATCA) as a novel biomarker/forensic biomarker for cyanide poisoning. METHODS: A sensitive method was developed and employed for the identification and quantification of ATCA in biological samples, where the sample extraction and clean up were achieved by solid phase extraction(SPE). After optimization of SPE procedures, ATCA was analyzed by high performance liquid chromatographytandem mass spectrometry. ATCA levels following the administration of different doses of potassium cyanide(KCN) to mice were measured and compared to endogenous ATCA levels in order to study the significance of using ATCA as a biomarker for cyanide poisoning.RESULTS: A custom made analytical method was established for a new(mice) model when animals were exposed to increasing KCN doses. The application of this method provided important new information on ATCA as a potential cyanide biomarker. ATCA concentration in mice plasma samples were increased from 189 ± 28 ng/mL(n = 3) to 413 ± 66 ng/mL(n = 3) following a 10 mg/kg body weight dose of KCN introduced subcutaneously. The sensitivity of this analytical method proved to be a tool for measuring endogenous level of ATCA in mice organs as follows: 1.2 ± 0.1 μg/g for kidney samples, 1.6 ± 0.1 μg/g for brain samples, 1.8 ± 0.2 μg/g for lung samples, 2.9 ± 0.1 μg/g for heart samples, and 3.6 ± 0.9 μg/g for liver samples. CONCLUSION: This finding suggests that ATCA has the potential to serve as a plasma biomarker / forensic biomarker for cyanide poisoning.

Synthesis of (2S,4S)-2-Substituted-3- (3-Sulfanylpropanoyl)-6- Oxohexahydropyrimidine-4-Carboxylic Acids as Potential Antihypertensive Drugs

Proceeding from natural amino acid L-asparagine and commercially available aldehydes a stereoselective synthesis was developed of (2S,4S)-2-alkyl(aryl)-3-(3-sulfanylpropanoyl)-6-oxohexahy- dropyrimidine-4-carboxylic acids, potential antihypertensive drugs, inhibitors of the angiotensin converting enzyme.

Structure and Luminescent Property of a Novel 4-Hydroxyquinoline-2-carboxylate Based Zn(Ⅱ) Complex

A 3D coordination polymer [Zn2（hqc）2（H2O）]n has been obtained from the reaction of 4-hydroxyquinoline-2-carboxylic acid （H2hqc） with zinc（II） salt under hydrothermal condition, and characterized by elemental analysis, IR, TGA, PXRD and X-ray single-crystal diffraction. The complex crystallizes in the monoclinic system, space group P21/c with a = 14.305（2）, b = 9.132（2）, c = 15.356（2）, β = 103.586（7）o, V = 1949.9（4）3, Z = 4, Dc = 1.782 g/cm3, μ = 2.508 mm-1, Mr = 523.06, F（000） = 1048, T = 293（2） K, λ（MoKα） = 0.71073, S = 1.008, the final R = 0.0329 and wR = 0.0745 for 3849 observed reflections （I 〉 2σ（I））. The title complex features a 3D framework via Zn（2） linking the 1D {Zn1（hqc）2}n chains. Thermogravimetric analysis shows that its framework is highly thermally stable up to 556 ℃ in the solid state.

Esterification and Chemoselective Synthesis of R-Tetrahydrothiazo-2-thione-4-carboxylic Esters Catalyzed by TiCl_4

A series of esters of R-tetrahydrothiazo-2-thione-4-carboxylic acid [ R-TTCA ] was synthesized by direct esterifica- tion of R-TTCA with alcohols（CH3OH, C2H5OH, n-C3HTOH, i-C3HTOH, n-C4H9OH, sec-C4H9OH） in the presence of TiCl4 as the catalyst at room temperature without using any other solvent or dehydrant in high yields, 91.6%-99.1% for primary alcohols and 55%- 80% for secondary alcohols. The catalyst has a strong chemoselec-tive activity for the esterification of primary alcohols with R-TTCA in the presence of secondary alcohols. Owing to high yield, high chemoselectivity, and mild conditions used, this is an efficient method for the esterification of prima-ry alcohols with R-TTCA.

Design, Synthesis, Antifungal Activities and SARs of （R）-2-Aryl-4,5-dihydrothiazole-4-carboxylic Acid Derivatives

Based on the structure of natural product 2-aryl-4,5-dihydrothiazole-4-carboxylic acid, a series of novel （R）-2-aryl-4,5-dihydrothiazole-4-carboxylic acid derivatives were designed and synthesized. Their structures were characterized by ^1H NMR, ^13C NMR and HRMS. The single crystal structure of compound 9b was determined by X-ray diffraction analysis. The antifungal activities were evaluated for the first time. The bioassay results indicated that most compounds exhibited moderate to good antifungal activities. The antifungal activities of compound 13a （against Cercospora arachidicola Hori）, 13d （against Alternaria solani）, and 16e （against Cercospora arachidieola Hori） were 61.9%, 67.3% and 61.9%, respectively, which are higher than those of the commercial fungicides chlorothalonil and carbendazim. Moreover, compound 13d exhibited excellent antifungal activities against 7 kinds of the fungi tested （66.7%, 77.3%, 63.0%, 87.9%, 70.0%, 70.0% and 80.0% at 50 μg/mL）. Therefore, 13d can be used as a new lead structure for the development of antifungal agents.

Resolution of racemic R.S-α-arylethylamine by a new resolving agent (R)thiazolidine-2-thione-4-carboxylic acid

Racemic R.S-α-arylethylamine was resolved by R (-) thiazolidine-2-thione-4-carboxylic acid, a new resolving agent abbreviated as [R (-) TTCA], by which R (-) TTCA.S(-) arylethylamine salts2a-2e, [α] D 20 =-47.24° — 64.40° and optically active R(+)-a-arylethylamines3a – 3e, 74. 54%-94. 45% e, e., were obtained. Optically active S (-) -α-arylethylamines4a-4e, 72.84%-90.36% e.e., were obtained by the decomposition of2a-2e in basic solutions. The influence of substitutive group of the benzene ring on the basicity of the amino group was studied by semiempirical PM3 method. The structures of the R (-) TTCA.S (-) -α-phenylethylamine salt (2a(R-S) configuration) and R (-) TTCA-R(+)-a-phenylethylamine salt (2a(R-R) configuration) have been established by means of X-ray diffraction. They crystallize in a monoclinic system. Space group isP21. The cell constants of2a(R-S) configuration were obtained as follows: α = 1.387 8(2), b = 0.664 05(101,c = 1.580 O(2) nm; β = 90.844(10)° Z = 4; those obtained for2a(R-R) configuration were α = 1.080 6(2),b = 0.584 80(12),c = 1.2188(2) nm, β= 110.38(3)dg, V = 0.7220nm3,Z = 2. There are intermolecular hydrogen bonds in the crystals of the two kinds of configurations of the amine salt. The hydrogen bond number in the unit cell of R (-) TTCA.S (-)-α-phenylethylamine salt is twice as much as that of R (-) TTCA.R(+)-a-phenylethylamine salt.

Synthesis,Structure,and Magnetic Property of One Snake-shaped Copper(Ⅱ)-organic Compound:Cu[Cu_2(PP)_2](CBPC)_2]·2(H_2O)

One novel copper（II）-organic compound,namely Cu[Cu2（PP）2]（CBPC）2]·2（H2O）（1,H2CBPC = 1-[（2＇-carboxybiphenyl-4-yl）methyl]-2-propylimidazole-4-carboxylic acid,HPP = 3-（2-pyridyl）pyrazole）,was designed and synthesized under hydrothermal conditions.X-ray diffraction analysis reveals that two Cu（II）ions in the quasi-planar dimmer of [Cu2（PP）2] are linked by the carboxylate oxygen atoms on the phenyl ring and the imidazole ring,respectively,yielding one snake-shaped structure.Magnetic measurements reveal that compound 1 shows the strongly antiferromagnetic property.Crystal data of 1：C58H52Cu3N10O10,Mr = 1239.72,monoclinic,P21/c,a = 14.900（7）,b = 15.029（7）,c = 12.308（6）,β = 102.519（9）o,V = 2691（2）3,Z = 2,Dc = 1.530 g/cm3,F（000）= 1274,μ = 1.246 mm-1,R = 0.0416,wR = 0.0780（I 2σ（I））and S = 0.999.

Hydrothermal Synthesis and Crystal Structure of One Novel 1-D Copper(Ⅱ)-organic Framework:{[Cu_2(PP)_2(CBPC)]_2·7H_2O}_n

One novel 1-D copper（Ⅱ）-organic compound,namely {[Cu2（PP）2（CBPC）]2·7H2O}n（1,H2CBPC=1-[（2＇-carboxybiphenyl-4-yl）methyl]-2-propylimidazole-4-carboxylic acid,HPP=3-（2-pyridyl）pyrazole）,was synthesized under hydrothermal conditions.X-ray diffraction analyses reveal that the two Cu（Ⅱ） ions in the distorted dimer [Cu2（PP）2] of 1 are linked by the carboxylate oxygen atoms on the phenyl and imidazole rings,respectively,forming one interesting snake-like chain.Single-crystal X-ray analyses reveal that it crystallizes in monoclinic,space group C2/c with a=30.656（8）,b=12.715（3）,c=22.405（5）,β=122.758（3）°,V=7344（3）3,Z=4,Mr=1681.65,Dc=1.521 g/cm3,F（000）=3464,μ=1.221 mm-1,the final R=0.0453 and wR=0.1023 for 4617 observed reflections with Ⅰ 〉2σ（Ⅰ）.

A Facile Synthesis of 9,10-Dimethoxybenzo[6,7]- ox-epino[3,4-<i>b</i>]quinolin-13(6<i>H</i>)-one and Its Derivatives

A concise and efficient method for the synthesis of novel 9,10-imethoxybenzo[6,7]oxepino[3,4-b]quinolin13(6H)-one and its derivatives 7a-p has been developed via the intramolecular Friedel-Crafts acylation reactions of 6,7-dimethoxy-2-(phenoxymethyl)quinoline-3-carboxylic acids 6a-p with polyphosphoric acid (PPA) as catalyst and solvent under mild conditions. The key intermediates 6a-p were prepared through the in situ formation of ethyl 6,7-dimethoxy-2-(phenoxymethyl)quinoline-3-carboxylates 5a-p followed by hydrolysis with aqueous ethanolic sodium hydroxide solution. The novel synthetic method has the advantages of good yields, easy work-up, and environmentally friendly character, which may provide a novel highly efficient process for making quinoline and related azaheterocycle libraries.

Indole Alkaloids from the Roots of Ervatamia hainanensis

Two new indole alkaloids, named ibogamine-18-carboxylic acid, 3, 4-didehydro-7, 8-dioxo-methyl ester 1, ibogamine-18-carboxylic acid, 16, 17-didehydro-9, 17-dihydro-9-hydroxy （2-oxopropyl）-methyl ester 2, were isolated from Ervatamia hainanensis. Their structures were elucidated on the basis of spectroscopic methods.

百尾参化学成分的分离与鉴定

目的研究百尾参Disporum cantoniense的化学成分。方法利用各种色谱技术进行分离,运用现代光谱技术鉴定化合物结构。结果从百尾参中分离得到16个化合物,分别鉴定为马来酸酰亚胺-5-肟(1)、4-methylene-5-oxopyrrolidine-2-carboxylic acid(2)、胸腺嘧啶(3)、腺嘌呤核苷(4)、5′-deoxy-5′-methylamino-adenosine(5)、乙基-α-L-鼠李糖(6)、岩白菜素(7)、4-羟基-2-甲氧基苯基-6-脱氧-α-L-吡喃木糖苷(8)、(-)-表儿茶素(9)、(6R,9R)-roseoside(10)、3-(4-羟基-3,5-二甲氧基苯基)-丙烷-1,2-二醇(11)、3-羟基-5-(p-羟基苯基)-戊酸(12)、1-核糖醇基-2,3-二酮-1,2,3,4-四氢-6,7-二甲基-喹喔啉(13)、(6S,9R)-vomifoliol(14)、3,4-二羟基苯酰甲醇(15)和1,2-二羟基-1-(4-羟基-3,5-二甲基苯基)-乙烷(16)。结论化合物1、2、5~9、12~16为首次从该属植物中分离得到;化合物1、2、5~10、12~16为首次从该植物中分离得到。

Three pairs of alkaloid enantiomers from the root of Isatis indigotica

Three pairs of enantiomerically pure alkaloids with diverse structure features, named isatindigoticoic acid A and epiisatindigoticoic acid A [(—)-1 and(+)-1], phaitanthrin A and epiphaitanthrin A [(—)-2 and(+)-2], and isatindopyrromizol A and epiisatindopyrromizol A [(—)-3and(+)-3], respectively, were isolated from an aqueous extract of the roots of Isatis indigotica. Racemic and scalemic mixtures of these enantiomers were separated by HPLC on a chiral semi-preparative column.Their structures including absolute configurations were determined by extensive spectroscopic analysis in conjunction with the calculation of electronic circular dichroism(ECD) spectra. The enantiomer pairs possess parent structures of 2-oxo-1,2,3,4-tetrahydroquinoline-4-carboxylic acid, indolo[2,1-b]quinazolinone, and 3-thioxohexahydro-1H-pyrrolo[1,2-c]imidazol-1-one, respectively. Except for phaitanthrin A[(—)-2] which the configuration was previously undetermined, these compounds are new enantiomeric natural products.

Constituents from the Roots of Semiaquilegia adoxoides

In present literature search, some cyano-containing compounds, which are very rare in plants, from the traditional anticancer herb Tiankuizi were reported. To find more cyano-containing compounds in the important plant Semiaquilegia adoxoides （DC） Makino （Chinese name Tiankuizi）, the isolation of the chemical constituents was investigated for advancing the research. Two new compounds, a new alkaloid, 1,2,3,4-tetrahydro-6-hydroxy-1[（3,4-dihydroxyphenyl）methyl]-7-methoxy-2,2-dimethyl-isoquinolinium, named Semiaquilegine A （1）, and a new ester, 3-（4＇-hydroxyphenyl）-2-propenoic acid （4＂-carboxyl）-phenyl ester （2）, and four cyano-containing compounds, （Z）-6a-（β-D-glucosyloxy）-4a,5a-dihydroxy-2-cyclohexene-△^1,a-acetonitrile （3）, （L0-6α-（β-D-glucosyloxy）-4α-hydroxy-2-cyclohexene-△^1,α-acetonitrile （4）, lithospermoside （5）, ehretioside B （6）, as well as eleven known compounds, were isolated from the roots of Semiaquilegia adoxoides. The structures of new compounds 1 and 2 were elucidated mainly by 1D/2D-NMR techniques. Very unusual cyano-containing compounds 3 and 4 were first isolated from Ranunculaceae family. Hitherto, there were six cyano-containing compounds found in the herb.