A novel class of compounds: synthesis of 5,5′-carbonyl-bis(5,6-dihydro-4H-furo- and thieno-[2,3-c]pyrrol-4-ones)

We hereby report the first synthesis of novel class of compounds, 5,5′-carbonyl-bis(5,6-dihydro-4H-thieno- and furo-[2,3-c]pyrrol-4-one starting from methyl 2-(2-methoxy-2-oxoethyl) thiophene- and furan-3-carboxylate, respectively. The ester functionalities connected to methylene group were regiospecifically converted to the desired monoacyl azides. Curtius rearrangement of acyl azides followed by hydrolysis of the formed isocyanates gave the symmetrical urea derivatives. Cyclization of the ester groups provided the target compounds.     

Efficient and library-friendly synthesis of furo- and thieno[2,3-d] pyrimidin-4-amine derivatives by microwave irradiation

A new, divergent, efficient, and selective synthesis of furo- and thieno[2,3-d]pyrimidin-4-amine derivatives by microwave irradiation has been developed starting from readily available amines and substituted 2-aminofuran-3-carbonitrile or 2-aminothiophene-3-carbonitrile, which are converted into corresponding formamidines in DMF using benzenesulfonyl chloride.     

Oxidation,With Chiral Retention,of Benzyloxycarbonyl Threonine Methyl Ester

A simple oxydative procedure converted Z-L-threonine methyl ester into the corresponding (2S)-β-keto ester: Starting material for the synthesis of labelled threonine derivatives.     

Cytotoxic evaluation of semisynthetic ester and amide derivatives of oleanolic acid

Although a number of chemicals have been isolated from Lantana camara, only a few have been evaluated for their biological significance. As part of our drug discovery program for cytotoxic agents from Indian medicinal plants, roots of L. camara L. were chemically investigated, which resulted in the isolation and identification of a cytotoxic agent, oleanolic acid (1b) as a major constituent. Oleanolic acid was converted into six semi-synthetic ester (2-7) and seven amide (8-14) derivatives. The ester derivatives (2-7) showed 3-6 times more selective activity than 1b against the human ovarian cancer cell line (IGR-OV-1), while amide derivatives 8-14 showed 16-53 times more selective activity against the human lung cancer cell line (HOP-62). Structure activity relationship within the ester (2-7) and amide (8-14) derivatives are discussed.     

Thiazolecarboxylic Acid Derivatives. 1. N-Substituted 2-Amino-4-methylthiazole-5-carboxylic Acid Derivatives

Acylation of the ethyl ester and anilide of 2-amino-4-methylthiazole-5-carboxylic acid gave 2-acetyl(arylsulfonyl)amino derivatives. Methylation of acetylaminothiazole and subsequent deacetylation gave 2-methylamino-4-methylthiazole-5-carboxylic acid, which was then converted into esters. The ethyl ester and anilide of thiazole-2-carboxylic acid were used as starting compounds for the synthesis of 2-dimethylaminoformimino- and 2-chlorobenzenesulfonylureido derivatives.     

The transformation using the soft NO⊕-species

The reaction of NaNO₂ in acidic solution with thiocarbonyl compounds has been studied. Secondary- and tertiary thioamides, 1-benzyl-hexahydro-2H-azepine-2-thione, 5-ethyl-5-phenyl thiobarbituric acid, certain thiourea derivatives, 2H-1-benzopyran-2-thione, O,O-diphenyl-thiocarbonic ester, O,S-diphenyl-dithiocarbonic ester, N,N-dimethyl-S-phenyl-dithiocarbamatic ester, N-ethyl-N-phenyl-O-ethyl-thiocarbamatic ester are all converted into the corresponding carbonyl-analogues. 4,4′-Bis (dimethylamino)-thiobenzophenone (Michler's thioketone) gives 3-nitro-4,4′-bis (dimethylamino)-benzophenone at room temperature. At (?10 °C)-(?5 °C) the expected oxo compound is obtained as the main product together with 4-(N-nitroso-methylamino)-4′-(dimethylamino)-benzophenone.     

Studies on Reactions of Cyclic Oxalyl Compounds with Hydrazines or Hydrazones. 2. Synthesis and Reactions of 4-Benzoyl-1-(4-nitrophenyl)-5-phenyl-1H-pyrazole-3-carboxylic Acid

4-Benzoyl-1-(4-nitrophenyl)-5-phenyl-1H-pyrazole-3-carboxylic acid, obtained from the corresponding furan-2,3-dione and N-benzylidene-N'-(4-nitrophenyl)hydrazine, was converted via reactions of its acid chloride with various alcohols or N-nucleophiles into the corresponding ester or amide derivatives. The nitrile of the starting acid and 1-(4-aminophenyl)-4-benzoyl-5-phenyl-1H-pyrazole-3-carboxylic acid were also obtained. While cyclocondensation reactions of the two acids and the nitrile mentioned with hydrazines lead to pyrazolo[3,4-d]pyridazine derivatives, the reaction of starting acid with 2-hydrazinopyridine provided the hydrazonopyrazole acid derivative.     

Diethylhydrogensilyl-cyclic diethylsilylene derivatives in gas chromatography-mass spectrometry of prostanoids. III. F alpha-prostaglandins and thromboxane B2 derivatives

The gas chromatographic (GC) and GC-mass spectrometric properties of the diethylhydrogensilyl-cyclic diethylsilylene (DEHS-DES) derivatives of prostaglandin (PG) F1 alpha methyl ester, PGF2 alpha methyl ester, 6-keto-PGF1 alpha methyl ester-alkyloxime and thromboxane (TX) B2 methyl ester-alkyloxime and the DES derivative of 13,14-dihydro-15-keto-PGF2 alpha methyl ester-alkyloxime were studied. When the ketonic PGs and TXB2 were converted into their methyloxime derivatives, the methylene unit values of these five prostanoid derivatives were slightly greater than those of the corresponding dimethylethylsilyl ether derivatives. When the ketonic PGs were converted into their corresponding ethyloxime derivatives, baseline separation was achieved in 20 min by use of a methylsilicone cross-linked fused-silica capillary column. The mass spectra of these derivatives were characterized by the ion at m/z 157 for F alpha prostaglandins and m/z 269 for TXB2. The major fragmentations were directed by the DES group, and other fragmentations common to the prostanoid derivatives were losses of an ethyl radical at the silicon atom, C5H11 hydrocarbon fragment, diethylhydrogensilanol and C15-C20 hydrocarbon fragment. The mass fragmentations of these prostanoid derivatives are briefly discussed. GC with high-resolution selected-ion monitoring was carried out for the TXB2 derivative at a resolution of 8000 by monitoring the ion at m/z 269.1573. A 25-pg amount of this derivative showed a well shaped doublet with a signal-to-noise ratio of more than 300:1.     

L-cysteine, a versatile source of sulfenic acids. Synthesis of enantiopure alliin analogues

[reaction: see text] l-Cysteine is a stimulating starting product for the generation of transient sulfenic acids, such as 4, 6, 9, and 15, which add to suitable acceptors, allowing formation of sulfoxides showing a biologically active residue. These sulfoxides are easily isolated in enantiomerically pure form. For instance, N-(tert-butoxycarbonyl)-l-cysteine methyl ester (1a) furnished in few steps sulfenic acid 9a, which was readily converted into (R,S(S))-(2-tert-butoxycarbonylamino-2-methoxycarbonyl-ethylsulfinyl)ethene (22), the methyl ester of Boc-protected nor-alliin. Moreover, the addition of 9a to 2-methyl-1-buten-3-yne has led to a sulfur epimeric and separable mixture of (R)-2-(2-tert-butoxycarbonylamino-2-methoxycarbonyl-ethylsulfinyl)-3-methyl-buta-1,3-dienes 10a and 11a, still possessing a "masked" sulfenic acid function, producible from their cysteine moieties once the dienes have been converted into the desired derivatives.     

New routes to 1α-hydroxyvitamin D3

The sulphone (2) and the methyl ester (3, R=H) were used in stereo-selective syntheses of derivatives of 1α-hydroxyprecalciferol₃ and 1α-hydroxytachysterol₃, which were then converted into the title compound.     

Highly efficient synthesis of β-amino esters via Mannich-type reaction under solvent-free conditions using ZnCl_2 catalyst

β-Amino esters were synthesized via ZnCl_2-catalyzed Mannich-type reaction of imines and malonate esters under solvent-free conditions in 6 min.Theβ-amino ester was converted into the corresponding aspartic acid derivatives.     

Novel pyrano[3,2-b]indole derivatives: synthesis and some properties

Acid treatment of β-(3-acetoxyindol-2-yl)-α-cyanoacrylic acid derivatives (ethyl ester and nitrile) with aqueous or gaseous HCl afforded novel 3-substituted 2-oxo-2,5-dihydropyra-no[3,2-b]indoles. 2-Oxo-2,5-dihydropyrano[3,2-b]indole-3-carbonitrile was converted into ethyl 2-oxo-2,5-dihydropyrano[3,2-b]indole-3-carboximidate.     

Spectral,Luminescent, and Photochemical Properties of Derivatives of Hydrogenated Furo- and Thienoquinolines

High Energy Chemistry - New derivatives of hydrogenated furo- and thioenoquinolines have been synthesized, and their spectral and luminescent properties and photochemical transformations have been...     

四正丁基过硫酸铵氧化裂解2，4-二硝基苯腙衍生物的反应研究

四正丁基过硫酸铵在1,2二氯乙烷溶剂中可高产率地使醛和酮的2,4-二硝基苯腙衍生物氧化裂解成相应的羰基化合物,其分子中碳碳双键,氰基,酯基和缩醛基等基团均不受影响。同时探讨了可能的反应机理和反应溶剂对氧化裂解反应的影响。     

Gas-liquid chromatographic analysis of protein amino acids as N-isobutyloxycarbonylamino acid methyl esters.

A practical method for the quantitative determination of protein amino acids by gas-liquid chromatography (GLC) is described. All of the common protein amino acids except arginine can be readily converted into their N-isobutyloxycarbonyl (N-isoBOC) methyl ester derivatives by a simple procedure involving isobutyloxycarbonylation with isobutyl chloroformate in aqueous medium, followed by methylation with diazomethane. Arginine was converted into N-isoBOC ornithine methyl ester by treatment with arginase, followed by the above derivatization procedure. The resulting N-isoBOC methyl esters of the amino acids have good GLC properties. Complete resolution of the derivatives of 20 protein amino acids was achieved by using a dual-column system consisting of a 0.65% Poly-A-101A column and a 0.70% FFAP-Poly-A-101A (1:1, w/w) column. The reproducibility of response was found to be good for derivatives carried through the entire chemical and chromatographic procedure. The calibration graphs were linear and showed no statistical bias. The results of recovery experiments with synthetic mixtures containing known amounts of the amino acids were satisfactory, the recoveries ranging from 94.3 to 106.2%.     

Determination of Enantiomeric Purity and Absolute Configuration of β-Lactams by High-Performance Liquid Chromatography on Chiral Columns

Enantiomers of β-lactams bearing aryl, furyl or styryl substituents in the 4-position were chromatographically separated by means of high-performance liquid chromatography on chiral column packed with amino acid-derived chiral stationary phase. Separation factors are generally modest. To improve further the resolution of enantiomers, the rings of these β-lactams were opened with octanol in acidic conditions and converted into N-3,5- dinitrobenzoyl ester derivatives of the resulting β-amino acids. Enantiomers of these derivatives are efficiently separated on an amide-derived chiral stationary phase. The chromatographic separations enable accurate determination of optical purity of the chiral β- lactams, prepared from homochiral ester enolate-imine condensation. The absolute configuration of the major enantiomer of the β-amino acid derivatives was determined from elution order on a chiral column.     

Synthesis of novel L-2',3'-dideoxy-2'-trifluoromethyl-4'- thiocytidines from alpha-trifluoromethyl-alpha,beta-unsaturated ester

A short and efficient synthesis of L-2',3'-dideoxy-2'-trifluoromethyl-4'-thiocytidines is described. (2R,4S/2S,4S)-5-(tert-Butyldimethylsiloxy)-2-trifluoromethylpentan-4-olide (3a and 3b) are prepared from alpha-trifluoromethyl-alpha,beta-unsaturated ester (1) in three steps and converted to compounds 6a and 6b. The corresponding 1-O-acetyl derivatives 8a and 8b were obtained via the usual Pummerer rearrangement from 6a and 6b in two steps, which were in turn used to synthesize L-4'-thiocytidines 10a and 10b.     

Derivatization of prostaglandins and related compounds to (methoxime) alkyl ester alkyl ether derivatives for gas chromatographic analysis

Rapid and convenient methods are described for the exhaustive derivatization of carbonyl, carboxyl and hydroxyl groups of prostaglandins and related compounds to methoxime, alkyl ester and alkyl ether compounds respectively. Optimal reaction conditions were established for each group. The reactions were carried out in polar aprotic solvents. Alkyl ester alkyl ether derivatives were obtained quantitatively and rapidly in one step with n-alkyl (C1-C4) halides in the presence of sodium hydroxide. Methyl ester methyl ether derivatives have the highest volatility, but propyl ester propyl ether derivatives improved the separation of complex mixtures. The carbonyl group sometimes induced side-products, so the carbonyl group was converted into methoxime. Methoximation was achieved quantitatively by using methoxylamine in the presence of hydrochloric acid or sodium hydroxide, followed by alkylation in same reaction medium. Methoximation gave syn- and anti-isomers, which were separated chromatographically, decreasing the resolution for complex samples.     

叶绿素-a及其衍生物的Qy轴向氧化反应和E-环重排反应

在酸碱性条件下对叶绿素-a (1)进行空气氧化反应, 分别得到卟吩衍生物2b～4b; 通过酯交换和去金属镁离子, 将叶绿素-a转化为脱镁叶绿酸-a甲酯(MPa) (5), 其3-位碳碳双键与氯化氢的加成生成卟吩醇(6), 经碱性空气氧化和E-环重排则转化成紫红素-18衍生物7. 选用四氧化锇和高碘酸钠将5氧化成卟吩醛(8), 在丁醇中以丁醇钠作催化剂, 8的氧化和重排反应给出3-甲酰基紫红素-18酯(9)和紫红素-7三甲酯衍生物10. 异构体4的空气氧化和重排反应也生成紫红素-18酯(3), 进一步与2-甲基丁胺进行缩合反应, 得到N-烷基紫红素-18酰亚胺(11a)以及氧化重排产物3-甲酰基-N-烷基紫红素-18酰亚胺(11b). 所得叶绿素衍生物均经UV, IR, 1H NMR及元素分析证明其结构, 并对相应的反应提出可能的反应机理.     

Furopyridines. XXII. Elaboration of the C-substituents alpha to the heteronitrogen atom of furo[2,3-b] -, -[3,2-b] -, -[2,3-c]- and -[3,2-c]pyridine

The Grignard reaction of fused ring cyanopyridine derivatives 1a-d with methyl- and phenylmagnesium bromide yielded the corresponding acylpyridine compounds 2a-d and 3a-d . Furopyridine N-oxides 4a-d were converted into the compounds having a phenyl group at the α-position to the ring nitrogen 5a-d . Reduction of 1a-d and the carboxylic esters 6a-d with diisobutylaluminium hydride yielded the corresponding amines 7a-d and aldehydes 9a-d . The aldehydes were converted to nitroethanol derivatives 10a-d by condensation with nitromethane and acrylic ester compounds 11a-d by the Wittig-Horner reaction with methyl diethyl phosphonoacetate.