Novel Synthetic Route of (2S)‐6‐Fluoro‐4‐oxo‐3,4‐dihydro‐2H‐chromene‐2‐carboxylic Acid

(2S)‐6‐Fluoro‐4‐oxo‐3,4‐dihydro‐2H‐chromene‐2‐carboxylic acid, a key intermediate of Fidarestat, was synthesized from natural chiral pool D‐mannitol. Its structure was confirmed by optical analyses, elemental analyses, and IR, ¹H NMR, and ESI‐MS spectra.     

Determination of thiazolidine-4-carboxylates in urine by chloroformate derivatization and gas chromatography-electron impact mass spectrometry

The derivatization method of thiazolidine-4-carboxylic acid (TZCA) and methyl-thiazolidine-4-carboxylic acid (Me-TZCA) in urine with alcohol/chloroformate was achieved. TZCA and Me-TZCA were derivatized in one step in urine with ethyl chloroformate in 1 min at room temperature. The derivatives of TZCA and Me-TZCA had very good chromatographic properties and offered very sensitive response for gas chromatography-electron impact ionization-mass spectrometry (GC-EI-MS). On the basis of derivatization, the method for simultaneous determination of TZCA and Me-TZCA in human urine was developed. Deuterated Me-TZCA (Me-TZCA-d(4)) was synthesized as the internal standard (IS) for the analysis of urine samples. TZCA and Me-TZCA were derivatized and extracted from urine at pH 9.5 with toluene, and then the dried extract was dissolved with 100 microl ethyl acetate and injected in GC/MS system. The recoveries of TZCA and Me-TZCA were about 102 and 103%, respectively, at the concentration of 0.05 mg/l. The method detection limits (MDL) were 1.0 and 0.5 microg/l, respectively, for TZCA and Me-TZCA in 1 ml human urine. The coefficients of variation of TZCA and Me-TZCA were less than 6% at the concentrations of 0.05 and 0.2 mg/l, respectively. To assess the formation of TZCA during inhalation with formaldehyde (FA) (about 3.1 and 38.1 ppm FA in air), urine samples from rats were taken during 3 days after initiation of treatment. The mean amount of TZCA determined was 0.07 mg/l in control group and 0.18 mg/l during treatment with 3.1 ppm. The TZCA levels increased up to about 1.01 mg/l during treatment with 38.1 ppm. It is planned to study whether urinary TZCA can be used as an indicator in the biological monitoring of exposure to FA.     

（R）—N—乙酰四氢噻唑—2—硫酮—4—羧酸与醇的反应

（Ｒ）－Ｎ－乙酰四氢噻唑－２－硫酮－４－羧酸与醇反应，在ＳＯＣｌ２存在下得到乙酸酯及四氢噻唑－２－硫酮－４－羧酸酯；在碳酸钾存在下得到乙酸酯及四氢噻唑－２－硫酮－４－羧酸；在二环己基碳二亚胺（ＤＣＣ）存在下得到缩水产物Ｎ－乙酰四氢噻唑－２－硫酮－４－羧酸酯。     

Analysis of 11-nor-Δ(9) -tetrahydrocannabinol-9-carboxylic acid and its glucuronide in urine by capillary electrophoresis/mass spectrometry

Δ⁹‐Tetrahydrocannabinol is the primary psychoactive component in cannabis, one of the most commonly used illicit drugs in the world. This paper describes a simple and rapid method for direct analysis of major metabolites of Δ⁹‐tetrahydrocannabinol; 11‐nor‐Δ⁹‐tetrahydrocannabinol‐9‐carboxylic acid and its glucuronide in urine by capillary electrophoresis/mass spectrometry. The only pretreatment needed for a urine sample was dilution with methanol containing an internal standard and centrifugation. Electrophoresis was carried out in an untreated fused‐silica capillary (50 µm i.d. × 85 cm) filled with 40 m m ammonium formate (pH 6.4). An analysis could be completed within 10 min. For both compounds, the assay was linear over the range 0.1 ? 10 µg/mL in urine with correlation coefficients (r²) > 0.99 and the limit of detection was 0.5 pg (10 nL injection). The detection yields and reproducibilities were determined at three different concentrations (0.1, 0.5 and 2 µg/mL in urine). The mean detection yields were 60 ? 99%. The intra‐ and inter‐day relative standard deviations of migration times were 0.063 ? 0.19 and 0.18 ? 0.36%, and those of peak areas were 4.2 ? 18 and 5.9 ? 25%, respectively. The proposed method successfully analyzed the urine samples of cannabis users. Copyright © 2012 John Wiley & Sons, Ltd.     

Novel affinity purification of monomeric sarcosine oxidase expressed in Escherichia coli

An efficient affinity‐purification protocol for Bacillus monomeric sarcosine oxidase (SOX) expressed in Escherichia coli BL21 (DE3) was developed. 4‐Aminopyrrole‐2‐carboxylic acid was chosen as the affinity ligand, which was coupled with Sepharose CL 4B via spacers composed of epichlorohydrin and ethylenediamine. With the affinity medium, the purification process consisted of only one affinity chromatography step to capture monomeric SOX. The purified SOX was 94 and 96% pure when analyzed on an HPLC Vydac C₈ column and reducing SDS‐PAGE. Meanwhile, the recoveries of typical SOX activity and protein were 90.8 and 37.5%, respectively, which were higher than other reported traditional protocols. Reducing SDS‐PAGE analysis revealed that the enzyme was a single polypeptide with the mass of ～46 kDa. The desorption constant K_d and theoretical maximum absorption Q_max were 35 μg/mL and 52.7 mg/g, respectively, in absorption analysis. All results indicated that the method would be of great potential for purifying monomeric SOX on an industrial scale.     

Synthesis, Characterization and Crystal Structure of [Na2(APZC)2(μ-H2O)2(μ3-H2O)]n

The synthesis and spectroscopic properties of a Na^＋ complex with ligand 3-aminopyrazine-2-carboxylic acid were described. The resulting complex was characterized by elemental analysis, IR, UV-Vis, NMR spectroscopy and single crystal X-ray diffraction method. The title compound crystallizes in the triclinic system with space group . The crystalline structure of this compound consists of supramolecular architectures involving strong intramolecular N—H…O in pyrazine molecules and intermolecular O—H…N, O—H…O, and N—H…N hydrogen bonds between substituted pyrazine and water molecules.     

Characterization of two hydroxytrichloropicolinic acids: application of the one-bond chlorine-isotope effect in 13C NMR

The structures of 4-hydroxy-3,5,6-trichloropyridine-2-carboxylic acid (1a) and 6-hydroxy-3,4,5-trichloro-2-carboxylic acid (1b) were verified by the NMR analysis of their corresponding methylated and decarboxylated derivatives 2,3,5-trichloro-4-methoxypyridine (5) and 3,4,5-trichloro-2-methoxypyridine (8), respectively. The 6-hydroxy isomer (1a) was found to be in equilibrium with its pyridinone tautomer as evidenced by the formation of significant amounts of 3,4,5-trichloro-1-methyl-6-oxo-1,6-dihydropyridine-2-carboxylic acid methyl ester (6b) on exhaustive methylation. The one-bond chlorine-isotope effect was used and shown to be an effective tool for the identification of chlorinated carbons in (13)C NMR spectra providing an additional tool for solving structural problems in chlorinated compounds.     

1H, 13C and 15N NMR spectroscopic characterization of unexpected degradation products of the nifedipine analogue bis(2‐cyanoethyl) 2,6‐dimethyl‐4‐(2‐nitrophenyl)‐1,4‐dihydro‐3,5‐pyridinedicarboxylate

In the course of saponification experiments with bis(2‐cyanoethyl) 2,6‐dimethyl‐4‐(2‐nitrophenyl)‐1,4‐dihydro‐3,5‐pyridinedicarboxylate ( 1 ), an analogue of the calcium channel blocker nifedipine, three unexpected degradation products were isolated. The compounds were identified as 3‐(2‐acetamido‐1‐carboxy‐1‐propenyl)‐1‐hydroxy‐2‐indolecarboxylic acid ( 3 ), 9‐hydroxy‐1,3‐dimethyl‐β‐carboline‐4‐carboxylic acid ( 4 ) and 6‐hydroxy‐2,4‐dimethyl‐5‐oxo‐5,6‐dihydrobenzo[c][2,7]naphthyridine‐1‐carboxylic acid ( 6 ). The structures of these compounds were deduced from one‐ and two‐dimensional ¹H, ¹³C and natural abundance ¹⁵N NMR experiments (¹H,¹H‐COSY, gs‐HSQC, gs‐HMBC, ¹⁵N gs‐HMBC), and corroborated by comparison of their NMR data with the respective data for structurally similar compounds. Copyright © 2002 John Wiley & Sons, Ltd.     

Complete 1H and 13C NMR assignments of the epimeric menthane-1-carboxylic acids

Complete NMR analyses with full assignments for (1)H and (13)C NMR spectral data for both epimers of menthane-1-carboxylic acid are described. The NMR properties of the recently synthesized axial isomer had not been previously described, and through use of a variety of 1D and 2D techniques, additional information is provided for the equatorial isomer. As well as assignments of chemical shifts, homonuclear coupling constants were determined for the equatorial isomer and most of coupling constants were measured for the axial isomer.     

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 arachidicola 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.     

微波辐射下的1,4-二甲基咔唑-9-羧酸的快速合成

以ＤＭＦ为溶剂,在微波辐射下由１,４－二甲基咔唑和相应的溴酯快速合成了两种１,４－二甲基咔唑－９－羧酸化合物,在最佳反应条件下,产率分别为８５．２％和８３．１％。     

Convenient Synthesis of tert‐Butyl Esters of Indole‐5‐carboxylic Acid and Related Heterocyclic Carboxylic Acids

The tert‐butyl esters of indole‐5‐carboxylic acid and related compounds such as benzofuran‐ and benzothiophene‐5‐carboxylic acid were readily accessed by reacting the appropriate carboxylic acids with tert‐butyl trichloroacetimidate. To obtain the tert‐butyl esters of the 5‐carboxylic acids of 1H‐benzotriazole and 1H‐benzimidazole, position 1 of these heterocycles had to be protected by acetylation prior to reaction with tert‐butyl trichloroacetimidate. Cleavage of the acetyl residue of the obtained intermediates by dilute aqueous NaOH in ethanol led to the desired tert‐butyl 1H‐benzotriazole‐and 1H‐benzimidazole‐5‐carboxylates.     

Syntheses of 9-Triptycylisothiocyanate, (10-Amino-9-triptycyl)carboxylic Acid,and Their Derivatives

In the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 9-triptycylisothiocyanate has been synthesized in 91% yield from carbon disulfide and sterically hindered 9-triptycylamine at room temperature. 9-Triptycylisothiocyanate can be further converted to 1-benzyl-3-(9-triptycyl)thiourea. (10-Amino-9-triptycyl)carboxylic acid has also been successfully synthesized via a three-step route starting from methyl 10-nitroanthracene-9-carboylate. Its amino and carboxylic groups can undergo acetylation and amidation, respectively.     

1,2,3-三唑取代的1,4-二氢-4-氧代-1,5-二氮杂萘-3-羧酸衍生物的设计、合成与HIV整合酶抑制活性评价

一价铜催化端炔与叠氮化物的1, 3-环加成反应是一种快速构建小分子库并筛选其可能性质的的主要方法。本文报道了1,2,3-三唑取代的1,4-二氢-4-氧代-1,5-二氮杂萘-3-羧酸衍生物的设计与合成。在该类化合物中,疏水性与亲水性片段通过Click反应有效地连接。所设计化合物8和12的结构通过光谱手段进行了表征;其可能的HIV整合酶抑制活性也进行了筛选。     

Simple and Convenient One‐Pot Synthesis of Benzimidazoles and Benzoxazoles using N,N‐Dimethylchlorosulfitemethaniminium Chloride as Condensing Agent

N,N‐Dimethylchlorosulfitemethaniminium chloride (SOCl₂‐DMF) has been found to be an efficient reagent for the one‐pot synthesis of benzimidazoles and benzoxazoles in excellent yield by condensation of carboxylic acids with o‐phenylenediamine/2‐amino‐phenol.     

1H and 13C NMR study of 2‐hydroxyglutaric acid and its lactone

Determination of the level and absolute configuration of 2‐hydroxyglutaric acid in a patient's urine is a method of diagnosing two metabolic diseases. Such a determination can be done with the aid of NMR spectroscopic methods. In this paper the careful interpretation of ¹H and ¹³C NMR spectra of this metabolite and its lactone measured under conditions used in biomedical assays is reported. The ¹H chemical shifts and spin–spin coupling constants were derived using the total lineshape analysis method. Copyright © 2002 John Wiley & Sons, Ltd.     

Differentiation of α‐COOH from β‐COOH in aspartic acids by N‐phosphorylation

The biomimic reactions of N‐phosphoryl amino acids, which involved intramolecular penta‐coordinate phosphoric‐carboxylic mixed anhydrides, are very important in the study of many biochemical processes. The reactivity difference between the α‐COOH group and β‐COOH in phosphoryl amino acids was studied by experiments and theoretical calculations. It was found that the α‐COOH group, and not β‐COOH, was involved in the ester exchange on phosphorus in experiment. From MNDO calculations, the energy of the penta‐coordinate phosphoric intermediate containing five‐member ring from α‐COOH was 35 kJ/mol lower than that of the six‐member one from β‐COOH. This result was in agreement with that predicted by HF/6‐31G** and B3LYP/6‐31G** calculations. Theoretical three‐dimensional potential energy surface for the intermediates predicted that the transition states 4 and 5 involving α‐COOH or β‐COOH group had energy barriers of ΔE=175.8 kJ?mol^?1 and 210.4 kJ?mol^?1, respectively. So the α‐COOH could be differentiated from β‐COOH intramolecularly in aspartic acids by N‐phosphorylation. © 2001 John Wiley & Sons, Inc. Int J Quant Chem 83: 41–51, 2001     

Syntheses and Crystal Structures of Copper(II) and Silver Complexes with 5‐Methyl‐1‐(4‐Methylphenyl)‐1,2,3‐Triazol‐4‐Carboxylic Acid

Two novel complexes [Cu L ₂(MeOH)] ( 1 )and [Ag₂ L (H L )₂(MeOH)] ( 2 ) ( L = 5‐methyl‐1‐(4‐methylphenyl)‐1,2,3‐triazol‐4‐carboxylic acid) were synthesized and characterized by elemental analysis, IR and X‐ray diffraction. Complex 1 is a mononuclear structure; the molecules were assembled into an infinite 2–D supramolecular by the C–H···O weak interactions. Complex 2 is a centrosymmetric dinuclear structure with bis(unidentate) carboxylato co‐ordination mode, and the molecules were assembled into 2–D layers by C–H···O and O–H···O weak interactions.     

R-四氢噻唑-2-硫酮-4-羧酸二聚反应的量子化学研究

R-四氢噻唑-2-硫酮-4-羧酸反应得到有光学活性的二聚体酰胺双四氢噻唑-2-硫酮并二氧代氢化吡嗪,用半经验量子化学PM3方法研究了反应物、中间产物和二聚体的电子结构.     

基于哌嗪与二羧酸/羟基羧酸的二元体系的超分子自组装

本文选择哌嗪 (pip) 为研究中心,分别和1,4-环己二甲酸 (H2chda)、间苯二甲酸(H2mpda)、6-羟基-2-萘甲酸 (Hohna)、1-羟基-2-萘甲酸 (Hshna) 进行超分子自组装,得到了四种新的氢键超分子体系：H2pip·chda (1), H2pip·2Hmpda (2), H2pip·ohna·2H2O (3),H2pip·shna (4)。单晶结构分析表明：1-3为三维氢键超分子结构,而 4为一维链状氢键结构。