Synthese und Struktur von Imino-bis[1]benzothiopyrano[4,3-b: 4,3-f] [1,5]dithiocinen

Synthesis and Structure of Imino-bis[1]benzothiopyrano[4,3-b:4,3-f][1,5]dithiocines Several substituted 3-Alkyl- respectively 3-Aryl-aminomethylene-2H-[1]benzothiopyran-4-thiones undergo a thermal reaction yielding the light yellow title compounds 2 . For the mechanism of this reaction we propose a condensation reaction of the starting compounds 1 loosing one molecule of amine in the first step followed by electrocyclisation reactions of the intermediates to products 2 . The structure of compounds 2 is elucidated by ¹H nmr spectroscopy and also x-ray analysis in case of compound 2b .     

A facile synthesis of some novel fused [1,2,4]triazolo[3,4-b][1,3,4]thiadiazol derivatives

A series of novel 3-[6-(4-substituted phenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-ylmethyl]-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-one derivatives (7a–7h) have been synthesized from 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (1) through a multi-step reaction sequence. The key intermediate (6) on condensation with various substituted aromatic carboxylic acids in the presence of phosphorus oxychloride afforded the series of title compounds (7a–7h). The structures of all newly synthesized compounds were established on the basis of their IR, ¹H-NMR, ¹³C-NMR and liquid chromatography mass spectrometry spectral data.     

Synthesis of Condensed Benzo[N,N]-Heterocycles by Microwave-Assisted Solid Acid Catalysis

The synthesis of several types of condensed benzo[N,N]-heterocycles such as benzimidazoles, benzodiazepines, quinoxalinones by a microwave-assisted solvent-free solid acid catalyzed method is described. The commercially available, inexpensive K-10 montmorillonite is an excellent catalyst for the synthesis of the target compounds. Our approach is based on the reactions of a wide variety of o-phenylenediamines, with ketones, aldehydes and bifunctional reagents, respectively. The cyclization reactions were initiated by microwave irradiation. The products, in most cases, were obtained in very high yields (up to 98%) and excellent selectivities in very short reaction times. The effective combination of solid acid catalysis, solvent-free conditions and microwave irradiation provides an attractive and highly ecofriendly approach for the synthesis of these important heterocycles.     

[4.4.1]Propellatetraene and Related Propellanes

Reaction of dichlorovinylene carbonate with 1,6-methano[10]annulene ( 2 ) followed by hydrolysis of the intermediate adduct afforded α-diketone 3 . Photolysis of 3 at liquid nitrogen temperature yielded the title compound, 1 . The activation parameters for the thermal isomerization 1 → 2 were ΔH⁺ = 5.1 kcal/mole and ΔS⁻= −19 eu (100 K). The structure of 3 was established by X-ray analysis. This analysis and MM2 calculations on a number of related compounds provide additional examples of the so-called “Klammer” effect in propellanes.     

NMR Study of the Dynamic Stereochemistry of Substituted Bicyclo[4.2.2]decanes and Bicyclo[5.2.2]undecane

Various NMR methods have been applied to investigate the ring-reversal process in the title compounds. In order to measure barriers an exact assignment of proton-exchange connectivities was required. This assignment was made using phase-sensitive NOESY and difference NOE and saturation transfer spectroscopies. The barriers for ring reversal were found to differ substantially between compounds 1–3 on one hand (9–10.5 kcal mol⁻¹), and compound 4 on the other (20.2 kcal mol⁻¹). This was rationalized in terms of the different geometries of the ring systems.     

Synthesis and In Silico Docking of New Pyrazolo[4,3-e]pyrido[1,2-a]pyrimidine-based Cytotoxic Agents

To explore a new set of anticancer agents, a novel series of pyrazolo[4,3-e]pyrido[1,2-a]pyrimidine derivativeshave been designed and synthesized viacyclocondensation reactions of pyrazolo-enaminone with a series of arylidenemalononitriles; compound 5 was obtained from 5-amino-4-cyanopyrazole. The structures of the target compounds were investigated by spectral techniques and elemental analysis (IR, UV–Vis, ¹H NMR, ¹³C NMR and ESI-MS). All compounds were evaluated for their in vitro cytotoxicity employing a panel of different human tumor cell lines, A375, HT29, MCF7, A2780, FaDu as well as non-malignant NIH 3T3 and HEK293 cells. It has been found that the pyrazolo-pyrido-pyrimidine analog bearing a 4-Br-phenyl moiety was the most active toward many cell lines with EC₅₀ values ranging between 9.1 and 13.5 µM. Moreover, in silico docking studies of the latter with six anticancer drug targets, i.e., DHFR, VEGFR2, HER-2/neu, hCA-IX, CDK6 and LOX5, were also performed, in order to gain some insights into their putative mode of binding interaction and to estimate the free binding energy of this bioactive molecule.     

Microwave-assisted synthesis of [Cr]APO-5

The synthesis of the chromium-substituted aluminophosphate [Cr]APO-5 (AFI) using microwave irradiation was investigated systematically. The prepared materials were characterized by chemical analysis (ICP-AES), XRD, SEM, DR–UV–Vis spectroscopy, and sorption of different probe molecules, i.e., water, benzene, and nitrogen. Stable chromium incorporation into the AFI-framework can be achieved up to a chromium content of at least 3.2 mol% (5.6 wt.%). Besides the content of chromium and water, the nature and content of co-templates such as acetic acid or ethylene glycol in the gel for the microwave-assisted synthesis were varied. The concentration of the co-template is a key factor for successful [Cr]APO-5 synthesis. The microwave-assisted crystallization of [Cr]APO-5 was completed within 30 min whereas the conventional hydrothermal crystallization took at least 6 h for completion. Nevertheless, the yields and quality of [Cr]APO-5 obtained from hydrothermal and microwave-assisted synthesis are comparable.     

Solid‐phase extraction of phenolic compounds with poly[metalloprotoporphyrin IX]

A highly insoluble metalloporphyrin polymeric material was used as sorbent for the solid‐phase extraction of phenolic compounds. Substantial quantities of phenols (40 to 60 mg/g polymer) were absorbed from aqueous solution comparing satisfactorily with other extraction methods. The polymeric phase presented similar K_SPE values for the hydrophobic compounds tested such as p‐chlorophenol, BPA, p‐nitrophenol, and a significant lower value for the more hydrophilic p‐aminophenol and cresol. Several metallic complexes of protoporphyrin IX (Co²⁺, Cu²⁺, Ni²⁺, Zn²⁺, and Fe³⁺) have been tested. The analytes were extracted with high recoveries at acid and neutral pH values, whereas at pH 10 low recoveries were obtained. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 81: 3038–3043, 2001     

Synthese und 13C-NMR-Spektroskopie einiger Pyrrolo[2,1-b]chinazoline

Synthesis and ¹³C-N.M.R.-Spectroscopy of Pyrrolo-[2,1,-b]quinazoline In 6- or 7-position substituted pyrrolo-[2,1-b]quinazoline derivatives were synthesized by reacting substituted anthranilic acid derivatives with either 4-amino-butyric acid or 2-methoxy-Δ¹-pyrroline. Furthermore some at C-3 substituted desoxyvasicinone derivatives were prepared. Using these compounds and different n.m.r. spectroscopie techniques the ¹³C resonance signals of all carbon atoms in peganine were assigned.     

A Versatile Synthetic Platform Based on Bicyclo[4.1.0]heptenes

Bicyclo[4.1.0]heptenes, which are readily accessible molecules via the transition metal-catalyzed cycloisomerization of 1,6-enynes, and have served as useful building blocks in organic synthesis. These molecules can undergo a variety of ring-opening reactions given that the release of the cyclopropyl ring strain (27.5 kcal/mol) may serve as a thermodynamic driving force for reactions, and the double bond within the skeleton can afford the kinetic opportunity to initiate the ring-opening via a coordination to a metal species. Even though the chemistry of the cyclopropyl group has been widely explored in organic chemistry, less attention has been paid to the chemistry of bicyclo[4.1.0]heptenes. However, during the past 5 years, we have been engaged in the exploration of the chemistry of bicyclo[4.1.0]heptenes. This review describes the chemistry developed in our laboratory. Depending upon the position, number, and identity of the substituent(s), the identity of the tether group, and the nature of the catalytic system, bicyclo[4.1.0]heptenes can undergo a variety of transformations. Our studies have revealed the reaction patterns of bicyclo[4.1.0]heptenes which include thermal reactions, nucleophilic addition, and rhodium-catalyzed reactions, that can proceed both with and without opening of the cyclopropyl ring. The chemistry described in this review can be used to produce a variety of new compounds such as 2,4-pentadienals, 3-methylene-4-vinylcyclohex-1-enes, bicyclo[3.2.2]nonadienes, 1,6,7,9a-tetrahydrocyclohepta[c] pyrans and -pyridines, hexahydroisoquinolines, 4-oxa-6-azatricyclo[3.3.0.0^2,8]octanes, and heterotricyclo[3.3.1.0^2,8]nonanes.     

Oxidation of p-[125I]Iodobenzoic Acid and p-[211At]Astatobenzoic Acid Derivatives and Evaluation In Vivo

The alpha particle-emitting radionuclide astatine-211 (²¹¹At) is of interest for targeted radiotherapy; however, low in vivo stability of many ²¹¹At-labeled cancer-targeting molecules has limited its potential. As an alternative labeling method, we evaluated whether a specific type of astatinated aryl compound that has the At atom in a higher oxidation state might be stable to in vivo deastatination. In the research effort, para-iodobenzoic acid methyl ester and dPEG₄-amino acid methyl ester derivatives were prepared as HPLC standards. The corresponding para-stannylbenzoic acid derivatives were also prepared and labeled with ¹²⁵I and ²¹¹At. Oxidization of the [¹²⁵I]iodo- and [²¹¹At]astato-benzamidyl-dPEG₄-acid methyl ester derivatives provided materials for in vivo evaluation. A biodistribution was conducted in mice with coinjected oxidized ¹²⁵I- and ²¹¹At-labeled compounds. The oxidized radioiodinated derivative was stable to in vivo deiodination, but unfortunately the oxidized [²¹¹At]astatinated benzamide derivative was found to be unstable under the conditions of isolation by radio-HPLC (post animal injection). Another biodistribution study in mice evaluated the tissue concentrations of coinjected [²¹¹At]NaAtO₃ and [¹²⁵I]NaIO₃. Comparison of the tissue concentrations of the isolated material from the oxidized [²¹¹At]benzamide derivative with those of [²¹¹At]astatate indicated the species obtained after isolation was likely [²¹¹At]astatate.     

Synthesis,Anticonvulsant, Sedative and Anxiolytic Activities of Novel Annulated Pyrrolo[1,4]benzodiazepines

Four new pentacyclic benzodiazepine derivatives (PBDTs 13–16) were synthesized by conventional thermal heating and microwave-assisted intramolecular cyclocondensation. Their anticonvulsant, sedative and anxiolytic activities were evaluated by drug-induced convulsion models, a pentobarbital-induced hypnotic model and an elevated plus maze in mice. PBDT 13, a triazolopyrrolo[2,1-c][1,4]benzodiazepin-8-one fused with a thiadiazolone ring, exhibited the best anticonvulsant, sedative and anxiolytic effects in our tests. There was no significant difference in potency between PBDT 13 and diazepam, and we proposed that the action mechanism of PBDT 13 could be similar to that of diazepam via benzodiazepine receptors.     

Novel Zinc(II) Complexes [Zn(atc-Et)2] and [Zn(atc-Ph)2]: In Vitro and in Vivo Antiproliferative Studies

Cisplatin and its derivatives are the main metallodrugs used in cancer therapy. However, low selectivity, toxicity and drug resistance are associated with their use. The zinc(II) (Zn^II) thiosemicarbazone complexes [Zn(atc-Et)₂] (1) and [Zn(atc-Ph)₂] (2) (atc-R: monovalent anion of 2-acetylpyridine N4-R-thiosemicarbazone) were synthesized and fully characterized in the solid state and in solution via elemental analysis, Fourier transform infrared (FTIR), ultraviolet-visible (UV-Vis) and proton nuclear magnetic resonance (¹H NMR) spectroscopy, conductometry and single-crystal X-ray diffraction. The cytotoxicity of these complexes was evaluated in the HepG2, HeLa, MDA-MB-231, K-562, DU 145 and MRC-5 cancer cell lines. The strongest antiproliferative results were observed in MDA-MB-231 and HepG2 cells, in which these complexes displayed significant selective toxicity (3.1 and 3.6, respectively) compared with their effects on normal MRC-5 cells. In vivo studies were performed using an alternative model (Artemia salina L.) to assure the safety of these complexes, and the results were confirmed using a conventional model (BALB/c mice). Finally, tests of oral bioavailability showed maximum plasma concentrations of 3029.50 µg/L and 1191.95 µg/L for complexes 1 and 2, respectively. According to all obtained results, both compounds could be considered as prospective antiproliferative agents that warrant further research.     

Regioselective synthesis and pharmacological activities of spirodibenzo[a,d]cycloheptene-5,2′-[1,3,4]thiadiazole derivatives

Some new 3^′,5^′-substituted-5H,3^′ H-spirodibenzo[a, d]cycloheptene-5,2^′-[1,3,4]thiadiazole and 10,11-dihydro-5H,3^′ H-spirodibenzo[a, d]cycloheptene-5,2^′-[1,3,4]thiadiazole derivatives 3a–n were regioselectively synthesized under 1,3-dipolar cycloaddition of 5-thiooxo-5H-dibenzo[a, d]cyclo-heptene and 5-thiooxo-10,11-dihydro-5H-dibenzo[a, d]cycloheptene with a variety of nitrilimines (generated in situ via dehydrohalogenation of the corresponding hydrazonoyl chlorides in the presence of triethylamine). The new products were tested for antiinflammatory, analgesic, and ulcerogenic score activities comparable to Indomethacin. Compounds 3i–l showed significant activity compared to Indomethacin.     

Electrochemistry and ion-sensing properties of calix[4]arene derivatives

The cyclic voltammetric properties of several substituted calix[4]arenes were examined in acetonitrile and dichloromethane. The compounds that contained one phenolic group in the macrocyclic cavity were able to be electrochemically oxidised at positive potentials. In acetonitrile, cyclic voltammetry experiments indicated that the phenolic compounds were oxidised in a two-electron (one-proton) process over all measured scan rates (up to 50 V s⁻¹), while in dichloromethane, the oxidation process occurred by one-electron at scan rates ≥5 V s⁻¹, to most likely form the radical cations. In both solvents, longer timescale (minutes to hours) controlled potential coulometry experiments indicated that the oxidation process occurred by two-electrons per molecule, to form reactive diamagnetic cations that could not be reduced back to the starting materials under electrolysis conditions. The ion-sensing properties of the compounds were investigated in polymer membrane ion-selective electrodes and it was found that they responded reversibly in a Nernstian fashion to Groups 1 and 2 metals and had the highest selectivity to the cesium cation.     

杯[4]芳烃咪唑盐的微波合成及在氟化反应中的应用

以杯[4]芳烃为起始原料,首先制得中间体杯[4]芳烃双溴代烷基衍生物,然后经微波辐射和阴离子交换,共得9种杯[4]芳烃咪唑盐衍生物,化合物的结构与构象经元素分析、IR、1HNMR、19FNMR、31PNMR表征.研究了它们在对氯硝基苯氟化反应中的催化性能以及对K+的萃取性能.结果表明,这9种化合物在氟化反应中的催化效果良好,对氟硝基苯的收率为80.89％～92.67％;同时化合物对K+具有较好的萃取效果,其中以化合物25,27-二[4-(3-甲基咪唑)乙氧基]-26,28-二羟基-5,11,17,23-四叔丁基杯[4]芳烃六氟磷酸盐的萃取效果最好,萃取率可达75.45％.     

Synthesis and photochemical reaction of benzo[a]quinoxalino[2,3‐c]phenazine dyes

Novel dyes based on the benzo[a]quinoxalino[2,3‐c]phenazine skeleton and necessary intermediates (benzo[a]phenazine‐5,6‐diones) were synthesized. The heterocyclic dyes and benzo[a]phenazine‐5,6‐diones were characterized using ¹H nuclear magnetic resonance (NMR) spectroscopy and chemical ion (CI) mass spectrometry. Their spectral properties, such as absorption and emission spectra and fluorescence quantum yield, were also measured. Experimental results demonstrated that photolysis of benzo[a]quinoxalino[2,3‐c]phenazine dyes in 2‐propanol and cyclohexene oxide leads to dihydro derivatives. The same product is formed during irradiation of dye/iodonium salt photoredox pairs in monomers. These compounds absorb incident light at longer wavelength and act as in situ sensitizers. Thus, when a composition was irradiated with a xenon lamp through a 395 cutoff filter, higher conversion was achieved than under monochromatic light.     

Ring closure reaction of 5-hydroxy-pyrido[2,3-d]pyrimidine-2,4,7-triones to benzo[b]pyrimido[4,5-h]1,6-naphthyridine-1,3,6-triones

N-Substituted aminouracils ( 1 ) react with malonates by cyclocondensation to 5-hydroxy-pyrido[2,3-d]pyrimidine-2,4,7-triones ( 2 ), which give with triethylorthoformate and aniline 6-(phenylaminomethylene)-pyrido[2,3-d]pyrimidine-tetraone ( 3 ). Halogenation of 2a - d (with R² = Me) with phosphorylchloride leads to 5,7-dichloro-pyrido[2,3-d]pyrimidine-2,4-diones ( 4 ) by cleavage of the methyl group at N-8, whereas Vilsmeier reaction of 2 affords 5-chloro-6-formyl derivatives ( 6 ), which cyclize with arylamines to give benzo[b]pyrimido[4,5-h] 1,6-naphthyridines ( 9 ). Compounds 9 were obtained independently by amination of the tosylates 5 to the 5-arylamino compounds 8 , and Vilsmeier formylation to yield 9 .     

Hexachloroplatinate(IV) anion-induced cucurbit[5]uril and cucurbit[8]uril supramolecular assemblies with linear channels

Two Q[n]-based porous compounds, Q[5]·[PtCl₆]^2 −·2H₃O·12H₂O and 2Q[8]·[PtCl₆]^2 −·2H₃O·74H₂O in cooperating the hexachloroplatinate(IV) anion ([PtCl₆]^2 −) as an inorganic structure directing agent are demonstrated. The driving forces for the formation of such novel Q[n]-based porous compounds are considered to be the outer surface interactions of Q[n]s, including dipole interactions between Q[n]s and ion-dipole interactions between [PtCl₆]^2 − anions and Q[n]s. Moreover, the Q[5]-based porous compound displays absorption distinctness for tetrachloromethane, whereas the Q[8]-based porous compound displays absorption distinctness for methanol.     

Synthesis and characterization of calix[4]arene-based copolyethers and polyurethanes. Ionophoric properties and extraction abilities towards metal cations of polymeric calix[4]arene urethanes

Copolyethers and polyurethanes containing lower and upper rim calix[4]arene units in the fixed cone conformation were prepared in good yield by polycondensation reactions of distal calix[4]arene diols with bisphenol-A/dibromomethane and 2,4-tolylendiisocyanate (TDI), respectively. In a similar way were prepared calix[4]arene-crown-5 and -crown-6 polyurethanes in the fixed 1,3-alternate conformation by condensation of TDI with lower rim calixcrown-5 and calixcrown-6 diols. However, the poor solubility in common organic solvents of the copolyether derivatives (M_w=11,100-11,600 g/mol) hampered further studies on their ionophoric properties. Aiming to obtain model compounds for the investigation of both extraction abilities and ionophoric properties of the polyurethane materials, several bis-urethanes were also synthesized by reaction of the calix[4]arene diols with p-tolylisocyanate (TI). The extraction ability measurements of monomeric and polymeric calix[4]arene urethanes (M_w=12,300-83,500 g/mol) towards alkali metal cations (Li⁺, Na⁺, K⁺, Rb⁺, Cs⁺) and Ag⁺showed a remarkable efficiency and selectivity of calixcrown-6 polyurethane toward Rb⁺, Cs⁺and Ag⁺.