Activated nitriles in heterocyclic synthesis: A Novel Synthesis of Pyrimidine Derivatives

The reaction of 3-amino-2,4-diethoxycarbonylcrotononitrile with cinnamonitrile derivatives afforded the pyrimidines 5a--d and not the pyridines 4 as expected from literature. Similarly pyrimidines 5e--h were produced when 3-amino-2,4-dicyanocrotononitrile was treated with the same reagent. The structure was established based on MS and high resolution ¹H-n.m.r. spectroscopy.     

Activated nitriles in heterocyclic synthesis: Novel Synthesis of Pyrimidine and of Pyridine Derivatives

α-Cyanochalcone reacted with thiourea and guanidine to yield the corresponding pyrimidine derivatives 2 and 4 . On the other hand, urea reacted with the same reagent under the same experimental conditions to yield the known urea derivatives 3 . A new synthesis of polyfunction pyridine via reaction of 1a with malononitrile in presence of aniline could be developed. Similar to the behaviour of 1a , Compounds 1b , c reacted with malononitrile in presence of aniline to yield compounds 8 and 9 . In contrast to the behaviour of compounds 1a – c , 1d reacted with malononitrile to yield the malononitrile derivatives 10 or 11 based on the reaction conditions. Mechanisms to account for formation of the reaction products were suggested.     

含噻二唑环吡唑并[3,4-d]嘧啶类含氟衍生物的合成及抗菌活性

通过5-氨基-4-氰基-1-苯基-1H-吡唑与三氟乙酸、三氯氧磷反应"一锅法"制得1-苯基-6-三氟甲基-4-氯-1H-吡唑并[3,4-d]嘧啶,收率为61%,再与5-芳基-2-巯基-1,3,4-噻二唑发生芳香族亲核取代反应合成8种含噻二唑环吡唑并[3,4-d]嘧啶类含氟衍生物,收率为79%～87%。目标化合物的结构经红外光谱、核磁共振氢谱、质谱与元素分析表征。并将其用于两种细菌(金黄色葡萄球菌和大肠埃希菌)的抑菌实验研究。结果表明,该类化合物对金黄色葡萄球菌均有抑制作用,其中化合物Ⅳb和Ⅳh的抑制活性相对较高。     

含噻二唑环噻吩并[2,3-d]嘧啶类含氟衍生物的合成及抗肿瘤活性

通过2-氨基-3-氰基噻吩与三氟乙酸、三氯氧磷反应"一锅法"制得2-三氟甲基-4-氯噻吩并[2,3-d]嘧啶,收率为60%,再与2-氨基-5-(取代苄硫基)-1,3,4-噻二唑发生芳香族亲核取代反应合成10个含噻二唑环噻吩并[2,3-d]嘧啶类含氟衍生物,收率为64%~75%。目标化合物的结构经红外光谱、核磁共振氢谱、质谱与元素分析表征,并采用MTT法对其进行初步的体外抗肿瘤活性筛选。结果表明,化合物Ⅳc和Ⅳf对Hep G2和BGC-823细胞的抑制活性高于对照样吉非替尼。     

新型吡唑衍生物1-甲基-4-乙氧羰基-5-羟基吡唑的合成

1-甲基-4-乙氧羰基-5-羟基吡唑是合成吡唑类HPPD酶抑制剂的-种很重要的有机合成中间体。笔者以丙二酸二乙酯与原甲酸三乙酯反应得到乙氧亚甲基丙二酸二乙酯,再与水合甲基肼反应、关环后得到1-甲基-4-乙氧羰基-5-羟基吡唑。探讨了反应温度及溶剂对反应的影响,以水为溶剂,反应温度为回流温度．收率较有机溶剂法有较大幅度提高。     

Effect of Antibiotic Amphotericin B Combinations with Selected 1,3,4-Thiadiazole Derivatives on RPTECs in an In Vitro Model

4-(5-methyl-1,3,4-thiadiazole-2-yl) benzene-1,3-diol (C1) and 4-[5-(naphthalen-1-ylmethyl)-1,3,4-thiadiazol-2-yl] benzene1,3-diol (NTBD) are representative derivatives of the thiadiazole group, with a high antimycotic potential and minimal toxicity against normal human fibroblast cells. The present study has proved its ability to synergize with the antifungal activity of AmB. The aim of this work was to evaluate the cytotoxic effects of C1 or NTBD, alone or in combination with AmB, on human renal proximal tubule epithelial cells (RPTECs) in vitro. Cell viability was assessed with the MTT assay. Flow cytometry and spectrofluorimetric techniques were used to assess the type of cell death and production of reactive oxygen species (ROS), respectively. The ELISA assay was performed to measure the caspase-2, -3, and -9 activity. ATR-FTIR spectroscopy was used to evaluate biomolecular changes in RPTECs induced by the tested formulas. The combinations of C1/NTBD and AmB did not exert a strong inhibitory effect on the viability/growth of kidney cells, as evidenced by the negligible changes in the apoptotic/necrotic rate and caspase activity, compared to the control cells. Both NTBD and C1 displayed stronger anti-oxidant activity when combined with AmB. The relatively low nephrotoxicity of the thiadiazole derivative combinations and the protective activity against AmB-induced oxidative stress may indicate their potential use in the therapy of fungal infections.     

Pyrolytic Reactions of Carbohydrates. Part IV. Anhydro-Sugar Formation and Transglycosylation in the Thermal Reactions of Various Glucose Derivatives

The formation of levoglucosan and 1,6-anhydroglucofuranose in the thermal decomposition of glucose derivatives, such as methyl and phenyl glucosides and oligosaccharides was studied. It was found that the cleavage of glucosidic linkages in general involves both transglycosylation and hydrolysis. Some conclusions relating to the thermal stability of the various glucosides were drawn and the mechanisms of the reaction are discussed.     

Synthesis and Characterization of Mesoporous Silica Functionalized with Calix[]arene Derivatives

This work reports a new method to covalently attach calix[4]arene derivatives onto MCM-41, using a diisocyanate as a linker. The modified mesoporous silicates were characterized by fourier transform infrared spectroscopy (FTIR), thermal analysis (TGA) and elemental analysis. The FTIR spectra and TGA analysis verified that the calix[4]arene derivates are covalently attached to the mesoporous silica. The preservation of the MCM-41 channel system was checked by X-ray diffraction and nitrogen adsorption analysis.     

1，3，4-噻二唑衍生物的合成和生物活性研究进展

1,3,4一噻二唑类杂环化合物不仅具有优良的杀虫,除草,抗植物病毒,杀菌、抗菌等多种生物活性,而且具有选择性好,活性高,毒性低,环境相溶性好等优点。故在医药和农药的研究和开发当中发挥着重要作用。习前,1,3,4-噻二唑类化合物已成为研制新农药的一个活跃领域,受到人们的广泛关注。因此,对具有杀菌活性的1,3,4-噻二唑化合物的分子设计、合成方法及其生物活性研究成为绿色新农药及药物研究的一个热点。文章对近年来的相关研究工作作一综述介绍。     

1,3,4-噁二唑-2-酮类化合物的合成及生物活性

研究合成了一系列5-苯基-3-氢-1,3,4-噁二唑-2-酮的衍生物,其结构经1H NMR和质谱确认.所有目标化合物经生物活性测试,发现具有一定的杀菌、杀虫活性.     

Reactions of acylium salts with aryl nitriles. A convenient Synthesis of Aryl Substituted bis- and tris-1, 3, 5-oxadiazinium salts

Bis-l, 3,5-oxadiaziniumalkanes ( 5a – u ) and tris-1, 3, 5-oxadiaziniumbenzene ( 6a – d ) were prepared from the reaction of diacylium and triacylium salts with aryl nitrites, respectively. All new compounds are fully characterized by spectroscopic methods and elemental analysis.     

Synthesis of Ecofriendly Functionalized Oxadiazole,Imidazole, Triazole and Pyridine Derivatives

5-Pentadecyl-1,3,4-oxadiazol-2-amine (2) was employed as key intermediate for the synthesis of some new functionalized five and six membered heterocyclic derivatives. The synthesized compounds were reacted with propylene oxide to obtain surface active agents having good surface activity, high solubility in water and good biodegradability. Moreover, the functionalized surfactants showed good antimicrobial activity against gram negative and gram positive organisms. The new compounds are easily synthesized, economical and environmentally friendly and are expected to constitute an important class of organic compounds for medicinal purposes in the future.     

α,β-Unsaturated nitriles in heterocyclic synthesis. II. Synthesis of Pyrazolo[3,4-b]pyridine and Pyrazolo[1,5-a]pyrimidine derivatives of antipyrine

5-Amino-3-antipyrinyl-pyrazole ( 1 ) reacted with cinnamonitriles 2a and 2c , d to afford 5-amino-4-benzylidene-pyrazole derivatives 3a , b . Compound 1 reacted with two moles of 2a to yield pyrazolo[3,4-b]pyridine derivative 7a which could be also obtained from the reaction of 3a with 2a . The reaction of 1 with α-cyanochalcone 2e resulted in the formation of pyrazolo-[1,5-a]pyrimidine derivative 8 .     

Ketene N,S-acetals in heterocyclic synthesis: Part 1: Synthesis of N-phenyl-2-ylidene and 2,5-diylidene-4-thiazolidinone derivatives

Ketene N,S-acetal potassium salts (2a–g), prepared via reaction of active methylenes (1a–g) with phenyl isothiocyanate in the presence of potassium hydroxide, were allowed to react with ethyl chloroacetate or chloroacetamide to afford the corresponding 2-ylidene-4-thiazolidinones (3a–g) in good yields. Compounds (3a–g) reacted with a variety of aromatic aldehydes to afford the corresponding 5-arylidene-2-ylidene-4-thiazolidinone derivatives (10a–e). Reaction of compound (3a) with triethylorthoformate afforded 5-ethoxymethylene-2-ylidene-4-thiazolidinone derivative (7), which was allowed to react with ammonia or phenyl hydrazine to give the corresponding enamino or hydrazino derivatives (8a) or (8b), respectively.     

Copper‐Catalyzed Highly Efficient Multicomponent Reactions of Terminal Alkynes,Acid Chlorides,and Carbodiimides: Synthesis of Functionalized Propiolamidine Derivatives

Functionalized propiolamidine derivatives were prepared in good to excellent yields under very mild conditions via a copper‐catalyzed multicomponent reaction (MCR) of readily available terminal alkynes, acid chlorides and carbodiimides with the assistance of triethylamine. The mechanism of this MCR is postulated.     

Photoreactions of Aromatic Compounds. XXXVII.1 Photosubstitution Reactions of Nitronaphthalene Derivatives

A systematic investigation was made of the photochemical properties of 12 fluoronitronaphthalenes and some methoxynitronaphthalenes in the presence of hydroxide ions, methoxide ions and methylamine. Results show that photosubstitution of fluorine in fluoronitronaphthalenes by methoxide or hydroxide must be a consequence of the activating effect of the nitro group. This effect is also clearly present when the nitro group and the fluorine atom are in different rings.     

Reactions of hydrazonoyl halides 44 [1]: synthesis of some new 1,3,4-thiadiazolines, 1,3,4-selenadiazolines and triazolino[4,3- a ]pyrimidines

1,3,4-Thiadiazolines, 1,3,4-selenadiazolines and triazolino[4,3-a]pyrimidines have been synthesized from 3-aza-[2,4-dimethyl(1,3-thiazol-5-yl)-2-bromo-3-substituted-amino]prop-2-en-1-ones with potassium thiocyanate, potassium selenocyanate, alkyl carbodithioates and 6-methyl-2-methylthio-4-substituted 3,4-dihydropyrimidine-5-carboxylates. Structures of the newly synthesized compounds have been established by elemental analysis, spectral data and alternative synthesis whenever possible. Some of products have been tested towards bacteria.