Abstract: Vitamin E, consisting of the groups of tocotrienols 5 and tocopherols 6, is the biologically most important fat-soluble antioxidant. In the context of total synthesis of these compounds,^[1] the Zr-mediated carboalumination methodology^[2] was applied. Alkyne 3, easily available from (E)-geranylacetone (4), delivers (all-E)-alkenyl iodide 2 for the coupling with (enantiomerically pure) aldehydes 1 to various stereochemically defined homologous trienols 5, e.g. serving as starting materials for the highly stereoselective Ir-catalyzed asymmetric hydrogenation to tocopherols 6.^[3] [1] a) T. Netscher, Chimia 1996, 50, 563; T. Netscher, Vitamins and Hormones 2007, 76, 155; b) C. Rein, P. Demel, R.A. Outten, T. Netscher, B. Breit, Angew. Chem. Int. Ed. 2007, 46, 8670; c) T. Netscher, M. Scalone, R. Schmid in Asymmetric Catalysis on Industrial Scale, H.-U. Blaser, E. Schmidt (eds.), Wiley-VCH, Weinheim, Germany, 2004, p. 71. [2] a) E. Negishi, Pure Appl. Chem. 1981, 53, 2333; b) S. Huo, E. Negishi, Org. Lett. 2001, 3, 3253. [3] S. Bell, B. Wüstenberg, S. Kaiser, F. Menges, T. Netscher, A. Pfaltz, Science 2006, 311, 642.

Abstract: In this paper we have investigated photocatalytic activity of the N, S-codoped TiO₂ nanoparticles for degradation of 4-NP in aqueous. In this method nitrogen and sulfur doping by using a single source, ammonium sulfate as the modification agent of titanium tetrachloride as precursor and the N, S-codoped TiO₂ nanoparticles prepared by the sol-gel method. This catalyst was characterized by XRD, SEM, UV- visible and FT-IR.

Abstract: Fluorescent cholic acid derivatives are used as well in biological investigations as in chemical. As nature products their derivatives can be used in research of hepatotoxicity, cell transport system and distribution of the drugs in organisms. Cholic acid-based fluorescent sensors are used to detection different organic and inorganic compounds such as drugs, toxins, amino acids and heavy metals. 'Fluorophore–spacer–receptor' motif is an effective way of designing of plurality of chemosensors and has used in the last two decades. Coumarines containing electron donating groups are natural non-toxic compounds that have good fluorescent parameters. It is also known that rearrangement of imino-coumarines is the easy way to fluorescent coumarine derivatives. Hence, in present work fluorescent receptor precursors bearing coumarine fluorophore on C24 of cholic acid were designed and synthesized in 3 steps. The condensation of 2-imino-coumarine-3-carboxamides with cholic hydrazide in acetic acid with following recyclization in diphenyl ether formed the corresponding 1,3,4-oxadiazol-2-yl-coumarin derivatives in moderate to good yields. Structures of synthesized 7 examples fluorescent cholic-based derivatives were confirmed by NMR H¹ and MS. The UV-absorption and fluorescent spectrum of the newly synthesized compounds was measured in acetonitrile and ethanol solutions. It is shown that wave length of emitted irradiation is in the range from 420 to 510nm and quantum yield is in the range from 0,02 to 0,58. Either wave length or quantum yields depend on donation value and position of substitution group in coumarine fragment. Sensor-precursors that are developed in this way are very flexible to modifications. On the one hand, it's possible to modify easily the coumarine fragment in order to change the wavelength of fluorescence and color, respectively, on the other hand, by the introduction of various substituents on the hydroxyl groups in cholic fragment it's allowed to control the response level from attaching guest-substances.

Abstract: Some new nitrogen bridge-head pyrido[1,2-b][1,2,4]triazepines incorporating 6-methylchromone moiety have been synthesized from the reaction of 1,6-diamino-4-(6-methyl-4-oxo-4H-chromen-3-yl)-2-oxo-1,2-dihydropyridine-3,5-dicarbonitrile (4) with some 1,3-bifunctional electrophiles including 2-cyano-3,3-bis(methylthio)acrylonitrile, 2-cyano-3,3-bis(methylthio)prop-2-enamide, 5-chloro-3-methyl-1-phenylpyrazol-4-carboxaldehyde, 2-chloro-3-formylquinoline, p-methoxybenzylidenemalononitrile, ethyl 2-cyano-3-(4-methoxyphenyl)prop-2-enoate and chromone-3-carbonitrile. Structure of the newly synthesized compounds have been establised on the basis of elemental analysis and spectral data. All compounds were screened in vitro for their antimicrobial activity.

Abstract: A novel class of backbone-modified oligonucleotide analogs has emerged since the discovery of Cu^I-catalyzed [3+2] azide-alkyne cycloaddition. These are oligonucleotide analogs with 1,4-substituted 1,2,3-triazoles in internucleotide linkages. Of all such analogs known to date, only the triazole-linked deoxythymidine decamer has been reported to show enhanced binding affinity to complementary DNA. Importantly, it is a fully modified (dT)₁₀ analog. Irregular oligonucleotides bearing the same backbone modification have not been described so far. With a goal of investigating sequence and regularity dependence of the effect of this modification on duplex stability, we have designed sequentially heterogenous modified oligonucleotides, which can be prepared using a modified dinuleoside block. In this paper we report on the synthesis of the dithymidine phosphoramidite block with the triazole linker, its utilization in oligonucleotide synthesis and hybridization data of thus obtained oligonucleotide analogs. The effect of single and multiple modifications on stability of irregular sequence duplexes is assessed and compared with published data for the oligo(T)/oligo(A) duplex. We also compare the effect of the linker concerned with that of a shorter triazole linker.

Abstract: This communication deals with the synthesis and evaluation of some pyrazinamide (PZA) analogues/prodrugs. A series of sixteen pyrazinamide analogues with the –CO-NH-CH₂- or -NH-CH₂- linkers connecting the pyrazine and benzene rings was prepared by using the microwave assisted coupling reaction of substituted methyl-pyrazinecarboxylate with ring-substituted benzylamines and characterized. The results of in vitro antimycobacterial screening indicated some interesting antimycobacterial activity in the series of N-benzylpyrazine-2-carboxamides. From the second series, 3-(3,4-dichlorobenzylamino)pyrazine-2-carboxamide was the most active in the inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts (IC₅₀ = 2.2 μmol mL^-1).

Abstract: Since the optically active quinuclidin-3-ol is an important intermediate in the preparation of physiologically or pharmacologically active compounds, new biocatalytic method for the efficient production of chiral quinuclidin-3-ols was examined. Butyrylcholinesterase (BChE; EC 3.1.1.8) was chosen as a biocatalyst in a preparative kinetic resolution of enantiomers. [1-3] In this study a series of racemic, (R)- and (S)- esters of quinuclidin-3-ol and acetic, benzoic, phthalic and succinic acids were synthesized as well as their racemic and chiral, quaternary N-benzyl, meta and para N-bromobenzyl and meta and para N-methylbenzyl derivatives. After the resolution, all N-benzyl protected groups were successfully removed by catalytic transfer hydrogenation with ammonium formate (10% Pd-C). The stereoselectivity of hydrolysis with horse serum BChE was investigated. The rates of hydrolyses were monitored at 37 ^oC in 0.1 M phosphate buffer pH 7.4 (2 mM concentrations of racemic esters). Hydrolyses studies confirmed [3] that all (R)-enantiomers of prepared esters are much better substrates than (S)-enantiomers. In the case of N-benzyl protected esters, the difference for all prepared esters was even more pronounced. Introduction of bromine atom or methyl group in the meta or para position on the phenyl ring of benzyl moiety resulted in a remarkable improvement of the stereoselectivity: (R)-acetates and (S)-alcohols were isolated in a high optical purity (> 95 %). Thus, optically pure quinuclidin-3-ols can be prepared in the high yields and enantiopurity by the esterification, quarternization with benzyl bromide, BChE-catalysed hydrolysis and finally catalytic transfer hydrogenation. [1] Ines Primozic, Tomica Hrenar, Srdjanka Tomic and Zlatko Meic, Journal of Physical Organic Chemistry 15 (2002) 608-614. [2] Ines Primozic, Tomica Hrenar, Srdjanka Tomic and Zlatko Meic, European Journal of Organic Chemistry (2003) 295-301. [3] Ines Primozic, and Srdjanka Tomic, Croatica Chemica Acta 84 (2011) 245-249.

Abstract: Phenolic compounds are bioactive substances widely distributed in the vegetable kingdom. They act as natural antioxidants, and their presence contributes to the color, flavor and aroma of food. This group of micronutrients is composed of one or more aromatic benzene rings with one or more hydroxyl groups and their redox properties are related with their chemical structure characteristics. The knowledge of their redox potentials may help the food industry, because when phenolic compounds are oxidized they could affect the quality of the wines, beers, grape juices, etc. Coumarins are a large family of compounds, of natural and synthetic origin, that show important biological activities. Therefore, they occupy an important place in the study of natural products and synthetic organic chemistry. Recent studies pay special attention to their antioxidative, anticarcinogenic and enzymatic inhibition properties. Their preparation, and the versatility of the synthetic methodology, allowed us obtaining a wide family of compounds with substituent in different positions in the molecule. The election of these derivatives has considered the later pharmacological evaluation. The investigation of the properties of these compounds, the study of the structural pattern and the elucidation of their biological role is of great interest for further development of coumarin-like antioxidant drugs. The electrochemical behaviour of a group of differently substituted hydroxycoumarins was investigated using cyclic, differential pulse and square wave voltammetry, in aqueous media at a glassy carbon electrode over the whole pH range. The antioxidant reactivity and capacity were also evaluated through a competition assay with hydroxyl radical (OH•) and DMPO like ORAC-FL methodology. Number and positions of the hydroxyl groups were important factors in the antioxidant activities against peroxyl radical of both types of coumarins derivatives.

Abstract: In a wide search program toward new antimicrobial agents, a seri of heterocyclic chalcones have been synthesized by condensing benzaldehyde derivatives with heteroarylmethylcetone in potassium hydroxide methanol according to the Claisen-Schmidt condensation at room temperature. The synthetic chalcones have been determined by IR spectroscopy and ¹H-NMR spectroscopy. The antimicro-bacterial activity of the novel products was evaluated against bacteria such as Staphylococcus aureus, Pseudomonas aeruginosae, E. coli and fungi such as Candida albicans, dermatophytes. The result shows that pyridine moiety may show antibacterial effect stronger than that of thiophene or furan. Heterocyclic chalcones with hydroxyl group on B ring at position 2 or 3 are considered as lead compounds for generation of new potential antimicrobial drugs in future.

Abstract: Over the last decades triterpenoids have drawn attention because of their anti-inflammatory, anti-oedematous, antitumor, and anti-HIV activities. Abundant in many plants, these metabolites are valuable natural raw materials to perform chemicals modifications and obtain semisynthetic analogs for structure-activity relationship studies. Asteraceae family constitutes a rich source of several pentacyclic mono-alcohols, diols and triols terpenes such as calenduladiol, faradiol, heliantriol B2, taraxasterol, arnidiol, lupeol, etc. Acetylcholine serves as a neurotransmitter in the central and peripheral nervous system. Acetylcholinesterase (AChE) stops the function of acetylcholine by its hydrolytic destruction in the cholinergic synapses. Enhancement of acetylcholine level in the brain inhibiting AChE is considered one of the most promising approaches for treating Alzheimer's disease. In the course of our ongoing search of natural AChE inhibitors, we isolated calenduladiol (1), in good yields, from ethanolic extract of Chuquiraga erinacea D. don. subsp. erinacea (Asteraceae), collected in southwest of Buenos Aires province, Argentina. This triterpene elicited moderate AChE inhibition which encouraged us to synthesize five calenduladiol derivatives: 30-oxo-calenduladiol (2), 30-hydroxy-calenduladiol (3), calenduladiol diacetate (4), 30-oxo-calenduladiol diacetate (5) and 30-hydroxy-calenduladiol triacetate (6). Compounds 2 and 3 were obtained by oxidation with SeO₂ and, 4, 5 and 6 by esterification with Ac₂O and pyridine from compounds 1, 2 and 3 respectively. Compounds 2-6 which were obtained in good yields and characterized by ¹H and ¹³C NMR spectroscopy. The oxidized analogs, 2 and 3 resulted to be the most active ones with a 43 % and 40 % of AChE inhibition at 0.2 mM, respectively, in the Ellman's assay. Acetylated derivatives (4-6) elicited a weak activity compared with 1, at the same concentration. Our results indicate that calenduladiol analogues oxidized at C-30 could be a promising strategy for the enhancement of pharmacological properties of this type of triterpene alcohols.

Abstract: The main objective of the project was to find conditions of the synthesis of pyrano[2,3-c]pyrazoles in accordance with the principles of "green" chemistry. Pyrano[2,3-c]pyrazoles possess a broad spectrum of biological activity. For example, they can be used as anticancer agents and enzyme inhibitors. Known methods for the synthesis of such compounds involve using large volumes of toxic solvents and are complicated in usage. In the course of the our work the reactions between malononitrile, 3-methyl-2-pyrazoline-5-one and benzaldehyde under solvent-free conditions and in small quantity of water in the presence of various amounts of non-toxic bases (potassium fluoride, sodium acetate, and sodium hydroxide) were studied. As a result, optimal conditions for the synthesis of 6-amino-3-methyl-4-phenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (one of the simplest pyrano[2,3-c]pyrazoles) have been found. These conditions were tested on synthesis of difficult functionally substituted pyrano[2,3-c]pyrazoles. Thus, it was found that in optimal conditions the reaction between malononitrile, 3-methyl-2-pyrazoline-5-one and aromatic aldehydes in small quantity of water and in the presence of 5 mol.% of sodium hydroxide leads to pyrano[2,3-c]pyrazoles selectively in high yield (more than 93%). Carrying out the reaction in water and using sodium hydroxide as the base allows to reduce the cost of the process and significantly improve its environmental friendliness. Using small amounts of water allows to use the working capacity of a chemical reactor more efficiently and to avoid significant losses at the isolation stage. Thus, the proposed process is more efficient and environmentally friendly compared to those known today.

Abstract: In this study a series of twenty-five substituted quinoline-2-carboxanilides were prepared. The procedures for synthesis of the compounds are presented. The compounds were tested for their activity related to inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. For all the compounds the structure-activity relationships (SAR) are discussed.

Abstract: In this study, a series of new seven ring-substituted 4-chloro-2-styrylquinazoline derivatives were prepared. The procedures for synthesis of the compounds are presented. The compounds were analyzed using RP-HPLC to determine lipophilicity. They were tested for their activity related to inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. For all the compounds, the relationships between the lipophilicity and the chemical structure of the studied compounds are discussed, as well as their structure-activity relationships (SAR).

Abstract: Camellia oil is used in cooking and soap making. The relative composition of the fatty acid components of the triglycerides is studied by NMR in Camellia Reticulata and Camellia Japonica.

Abstract: Neurodegenerative diseases are becoming prevalent pathologies in developed societies due to increasing average of life expectancy of the population. This fact has encouraged an active research in the development of new drugs, since they may represent an important advance in the treatment of complex diseases such as Alzheimer and Parkinson's diseases. Coumarins are a large family of compounds, of both natural and synthetic origin, important because of the pharmacological activities that this compounds display. Therefore, they occupy an important place in the organic and medicinal chemistry realm. In recent years, coumarins have been attracting interest because of their ability of inhibiting some enzymes. The versatility of the Perkin and Knoevenagel reactions has led to a large family of differently substituted compounds. In order to find the structural features for the human MAO inhibitory activity and selectivity, in the present communication we report the synthesis, pharmacological evaluation and a comparative study of a new series of 3-phenylcoumarins versus 3-benzoylcoumarins. A bromo atom and a methoxy/hydroxy substituent were introduced in these scaffolds at different positions of the coumarin moiety. The synthesized compounds were evaluated as MAO-A and B inhibitors using R-(-)-deprenyl and iproniazide as reference compounds. The presence or absence of a carbonyl group between the coumarin and the phenyl substituent in 3 position remarks, respectively, the MAO-A or MAO-B inhibitory activity. Some of the new compounds showed MAO-B inhibitory activities in the low nanomolar range. Compound 2 (IC₅₀ = 1.35 nM) showed higher inhibitory activity than the R-(-)-deprenyl (IC₅₀ = 19.60 nM) and higher MAO-B selectivity, with more than 74,074-fold inhibition level, respecting to the MAO-A isoform. In addition, docking experiments were carried out on hMAO-A and h-MAO-B structures. This study has provided new information about the enzyme-inhibitor interaction and the potential therapeutic application of this coumarin scaffolds.