A convenient synthesis of 5-benzylidenethiazolidine-2, 4-diones under microwave irradiation without solvent

A series of 5-benzylidenethiazolidine-2,4-diones was synthesised by the Knoevenagel condensation of aromatic aldehydes with thiazolidine-2,4-dione in the presence of catalytic amounts of piperidine and acetic acid under microwave irradiation without solvent in good yields.

Mechanistic studies on the degradation of gasoline oxygenates by advanced oxidation technologies and the reaction of 4-methyl-1,2,4-triazoline-3,5-dione with tetracyclopropylethylene

Gasoline oxygenates (MTBE, methyl tert-butyl ether; DIPE, di-isopropyl ether; ETBE, ethyl tert-butyl ether; TAME, tert-amyl ether) are added to gasoline to boost octane and enhance combustion. The combination of large scale use, high water solubility and only minor biodegradability has now resulted in a significant gasoline oxygenate contamination occurring in surface, ground, and drinking water systems. Combination of hydroxyl radical formation and the pyrolytic environment generated by ultrasonic irradiation (665 kHz) leads to the rapid degradation of MTBE and other gasoline oxygenates in aqueous media. ^ The presence of oxygen promotes the degradation processes by rapid reaction with carbon centered radicals indicating radical processes involving O 2 are significant pathways. A number of the oxidation products were identified. The formation of products (alcohols, ketones, aldehydes, esters, peroxides, etc) could be rationalized by mechanisms which involve hydrogen abstraction by OH radical and/or pyrolysis to form carboncentered radicals which react with oxygen and follow standard oxidation chain processes. ^ The reactions of N-substituted R-triazolinediones (RTAD; R = CH 3 or phenyl) have attracted considerable interest because they exhibit a number of unusual mechanistic characteristics that are analogous to the reactions of singlet oxygen (1O2) and offer an easy way to provide C-N bond(s) formation. The reactions of triazolinedione with olefins have been widely studied and aziridinium imides are generally accepted to be the reactive intermediates. ^ We observed the rapid formation of an unusual intermediate upon mixing tetracyclopropylethylene with 4-methyl-1,2,4-triazoline-3,5-dione in CDCl 3. Detailed characterization by NMR (proton, 13C, 2-D NMRs) indicates the intermediate is 5,5,6,6-tetracyclopropyl-3-methyl-5,6-dihydro-oxazolo[3,2- b][1,2,4]-triazolium-2-olate. Such products are extremely rare and have not been studied. Upon warming the intermediate is converted to 2 + 2 diazetidine (major) and ene product (minor). ^ To further explore the kinetics and dynamics of the reaction activation energies were obtained using Arrhenius plots. Activation energies for the formation of the intermediate from reactants, and 2+2 adduct from the intermediate were determined as 7.48 kcal moll and 19.8 kcal mol−1 with their pre-exponential values of 2.24 × 105 dm 3 mol−1 sec−1 and 2.75 × 108 sec−1, respectively, meaning net slow reactions because of low pre-exponential values caused by steric hindrance. ^

Neue und selektive GSTP1-Inhibitoren mit 1,2,4-Trioxanstruktur als Grundlage für die Entwicklung einer effektiven Tumortherapie

Im Rahmen dieser Arbeit wurden selektive Inhibitoren der Glutathion-Transferase P1 (GSTP1) mit 1,2,4-Trioxanstruktur als potentielle Wirkstoffe gegen multiresistente Tumore synthetisiert. Die Darstellung dieser Substanzen erfolgte über Typ-II-Photooxygenierung allylischer Alkohole mit anschließender Säure-katalysierter Peroxyacetalisierung unter Verwendung von 4-Nitrobenzaldehyd. Über diesen Syntheseweg konnten unterschiedlich substituierte 1,2,4-Trioxane dargestellt werden. Die höchste biologische Aktivität zeigten Verbindungen mit aromatischen Estersubstituenten am 1,2,4-Trioxanring. Es wurde eine Leitstruktur entwickelt, die einen α,β-ungesättigten aromatischen Estersubstituenten in Position 6 des 1,2,4-Trioxangerüsts und in Position 3 einen 4-Nitrophenylsubstituenten aufweist. Die Verbindungen dieser Substanzklasse zeigen Inhibition der GSTP1 im niedrig mikromolaren Bereich. Durch Aktivitätsstudien an den GST-Klassen A und M konnte gezeigt werden, dass die Verbindungen selektiv GSTP1 inhibieren. Nachdem mittels quantitativer PCR 12 Krebszelllinien, die hohe GSTP1-Expressionsniveaus zeigen, identifiziert worden waren, wurde die Aktivität der 1,2,4-Trioxane gegenüber GST, die in Krebszelllysaten vorkommt, nachgewiesen. Die GST in der Brustkrebsepithelzelllinie HBL100 und der Lungenkarzinomzelllinie SK-MES-1 wird durch 1,2,4-Trioxane noch effektiver inhibiert als aufgereinigte GSTP1 (IC50 im nanomolaren Bereich).

CIL I(2): 2.4, 2965 – Epitaph of Sextus Aemilius Baro, a grain merchant

Squeeze and photograph

Selective Sonogashira Couplings in 1,2,4,5-tetrazine derivatives

1,2,4,5-Tetrazines are six-membered heterocyclic compounds in which the four nitrogen atoms are displayed in a symmetric fashion. Their reactivity is quite different from other heterocyclic aromatic systems due to its unique electron-withdrawing character, comparable to tetra-nitrobenzene. 1 In particular, 1,2,4,5- tetrazines are known to take part in [4+2] inverse-Diels–Alder cycloaddition processes which efficiently lead to the construction of substituted pyridazine systems that are important in drug development and biomarker applications. 2 However, the electronic character of 1,2,4,5-tetrazines hampered the development of 3- ethynyl- and 3,6-diethynyl-1,2,4,5-tetrazine derivatives for molecular electronic applications, proved by the scarcity of examples found in the literature. 3 Herein, we describe the synthesis and characterization of two novel ethynyl-based 1,2,4,5-tetrazine derivatives. Synthesis of 3,6-(4-bromophenyl)-1,2,4,5-tetrazine precursor (1) was achieved in good yield by Pinner’s method, starting from 4-bromobenzonitrile. Despite its low solubility in common organic solvents, this precursor was found to react smoothly under typical Sonogashira coupling conditions to selectively afford the 3-ethynyl (2) and 3,6-diethynyl (3) protected derivatives (Figure 1). Reaction conditions were evaluated in order to provide the best yields and to promote selectivity of the mono- or disubstituted ethynyl derivatives. Finally, deprotection was achieved affording, in the case of compound 3, an unprecedented 3,6- diethynyl-1,2,4,5-tetrazine compound. Time-Dependent Density Functional Theory (TDDFT) calculations for both deprotected ethynyl derivatives were used to simulate electronic spectra. A deep knowledge of the relevant electronic transitions involved and quantitatively satisfactory results of the calculated electronic excitations in comparison with experimental data were obtained.

Crystal Structure Of (3e)-3-(2,4-di-nitro-phen-oxy-meth-yl)-4-phenyl-but-3-en-2-one.

In the title compound, C17H14N2O6, the conformation about the C=C double bond [1.345 (2) Å] is E, with the ketone moiety almost coplanar [C-C-C-C torsion angle = 9.5 (2)°] along with the phenyl ring [C-C-C-C = 5.9 (2)°]. The aromatic rings are almost perpendicular to each other [dihedral angle = 86.66 (7)°]. The 4-nitro moiety is approximately coplanar with the benzene ring to which it is attached [O-N-C-C = 4.2 (2)°], whereas the one in the ortho position is twisted [O-N-C-C = 138.28 (13)°]. The mol-ecules associate via C-H⋯O inter-actions, involving both O atoms from the 2-nitro group, to form a helical supra-molecular chain along [010]. Nitro-nitro N⋯O inter-actions [2.8461 (19) Å] connect the chains into layers that stack along [001].

Inhibition Of Tumor Necrosis Factor-alpha And Cyclooxigenase-2 By Isatin: A Molecular Mechanism Of Protection Against Tnbs-induced Colitis In Rats.

Isatin, an indole alkaloid has been shown to have anti-microbial, anti-tumor and anti-inflammatory effects. Due to its findings, we evaluated whether this alkaloid would have any effect on TNBS-induced colitis. Animals (male Unib:WH rats, aged 8 weeks old) were induced colitis through a rectal administration of 2,4,6-trinitrobenzene sulphonic acid using a catheter inserted 8 cm into the rectum of the animals. The rats were divided into two major groups: non-colitic and colitic. The colitic group was sub-divided into 6 groups (10 animals per group): colitic non-treated, Isatin 3; 6; 12.5; 18.75 and 25 mg/kg. Our main results showed that the oral treatment with Isatin 6 and 25 mg/kg were capable of avoiding the increase in TNF-α, COX-2 and PGE₂ levels when compared to the colitic non-treated group. Interestingly, the same doses (6 and 25 mg/kg) were also capable of preventing the decrease in IL-10 levels comparing with the colitic non-treated group. The levels of MPO, (an indirect indicator of neutrophil presence), were also maintained lower than those of the colitic non-treated group. Isatin also prevented the decrease of SOD activity and increase of GSH-Px and GSH-Rd activity as well as the depletion of GSH levels. In conclusion, both pre-treatments (6 and 25 mg/kg) were capable of protecting the gut mucosa against the injury caused by TNBS, through the combination of antioxidant and anti-inflammatory properties, which, together, showed a protective activity of the indole alkaloid Isatin.

Antioxidant and antimicrobial properties of 2-(4,5-dihydro-1H-pyrazol-1-yl)-pyrimidine and 1-carboxamidino-1H-pyrazole derivatives

Five previously synthesized 4-trifluoromethyl-2-(5-aryl-3-styryl-1H-pyrazol-1yl)-pyrimidines and six 5-aryl-3-styryl-1-carboxamidino-1H-pyrazole derivatives were screened for their antioxidant proprieties. The antioxidant activities were evaluated by using the DPPH and the HRP/luminol/H2O2 chemiluminescence assay systems and for their antimicrobial activity (MIC). The results were good for those series in some concentration in comparison with the standards.

2-(4-Methoxyphenylsulfinyl)cyclohexan-1-one

The cyclohexanone ring in the title compound, C(13)H(16)O(3)S, is in a distorted chair conformation. The intramolecular S center dot center dot center dot O(carbonyl) distance is 2.814 (2) angstrom. Molecules are connected into a two-dimensional array via C-H center dot center dot center dot O contacts involving the carbonyl and sulfinyl O atoms.

Distribution of interleukin-2,-4,-10, tumour necrosis factor-alpha and transforming growth factor-beta mRNAs in oral lichen planus

In the present study. MRNA for the cytokines interleukin-2 (IL-2), IL-4, IL-10 tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor beta-1 (TGF-beta-1) were investigated in oral lichen planus (OLP) lesions using in situ hybridization with S-35-labelled oligonucleotide probes on frozen tissue sections. In addition, the expression of interferon-gamma (IFN-gamma), IL-10 and IL-4 mRNAs was analysed in cultured lesional T lymphocytes from oral lichen planus by polymerase chain reaction. Cells expressing mRNA for IL-2, IL-4, IL-10, TNF-alpha and TGF-beta(1) were found in all the biopsies studied. Approximately 1-2% of the total number of infiltrating cells in the lesions were positive for each of the different cytokine mRNAs. Most biopsies contained basement membrane-oriented, mRNA-positive cells. In the cultured T-cell lines, message for IFN-gamma was detected in all the patients, IL-10 in all but one, and IL-4 in just one of the seven patients investigated. The results suggest that mRNA for both pro- and anti-inflammatory cytokines, i.e., mixed T-helper 1 (T(H)1) and T(H)2 cytokine profiles, are generated simultaneously by a limited number of cells in chronic lesions of OLP. (C) 1999 Elsevier Science Ltd. All rights reserved.

Potential GABAB receptor antagonists .9. The synthesis of 3-amino-3-(4-chlorophenyl)propanoic acid, 2-amino-2-(4-chlorophenyl)ethylphosphonic acid and 2-amino-2-(4-chlorophenyl)ethanesulfonic acid

This paper describes the synthesis of 3-amino-3-(4-chlorophenyl)propanoic acid and the corresponding phosphonic and sulfonic acids, lower homologues of baclofen, phaclofen and saclofen respectively. The chlorinated acids were all weak specific antagonists of GABA at the GABAB receptor, with the sulfonic acid (pA(2) 4.0) being stronger than the phosphonic acid (pA(2) 3.8) and carboxylic acid (pA(2) 3.5).