No-solvent Condensation Reaction of Amino Acids and their Derivatives with Pyrandione

Pyrandione rings are contained within a number of natural products1, pharmaceutical intermediates2 and agrochemicals3. They have drawn great interest recently because some of them have high activity of inhibiting HIV protease4. We have reported the fungicidal activity of 15. Later we found that 2 also could inhibit S. Sclerotiorum (85.7% at a concentration of 500 ppm). This result led us to study the biological activity of the derivatives of this kind of compounds. We have synthesized a ser…     

Molecular Docking,DFT Calculations,Effect of High Energetic Ionizing Radiation,and Biological Evaluation of Some Novel Metal (II) Heteroleptic Complexes Bearing the Thiosemicarbazone Ligand

New Pb(II), Mn(II), Hg(II), and Zn(II) complexes, derived from 4-(4-chlorophenyl)-1-(2-(phenylamino)acetyl)thiosemicarbazone, were synthesized. The compounds with general formulas, [Pb(H₂L)₂(OAc)₂]ETOH.H₂O, [Mn(H₂L)(HL)]Cl, [Hg₂(H₂L)(OH)SO₄], and [Zn(H₂L)(HL)]Cl, were characterized by physicochemical and theoretical studies. X-ray diffraction studies showed a decrease in the crystalline size of compounds that were exposed to gamma irradiation (γ-irradiation). Thermal studies of the synthesized complexes showed thermal stability of the Mn(II) and Pb(II) complexes after γ-irradiation compared to those before γ–irradiation, while no changes in the Zn(II) and Hg(II) complexes were observed. The optimized geometric structures of the ligand and metal complexes are discussed regarding density functional theory calculations (DFT). The antimicrobial activities of the ligand and metal complexes against several bacterial and fungal stains were screened before and after irradiation. The Hg(II) complex has shown excellent antibacterial activity before and after γ-irradiation. In vitro cytotoxicity screening of the ligand and the Mn(II) and Zn(II) complexes before and after γ-irradiation disclosed that both the ligand and Mn(II) complex exhibited higher activity against human liver (Hep-G2) than Zn(II). Molecular docking was performed on the active site of MK-2 and showed good results.     

Carboxylic Acids from <Emphasis Type="Italic">Phyllanthus urinaria</Emphasis>

Five compounds, terephthalic acid mono-[2-(4-carboxy-phenoxycarbonyl)-vinyl] ester (1), (E)-3-(5′-hydroperoxy-2,2′-dihydroxy[1,1′-biphenyl]-4-yl)-2-propenoic acid (2), 3,4,5-trihydroxybenzoic acid (3), succinic acid (or butanedioic acid) (4), and 2,3,4,5,6-pentahydroxybenzoic acid (5), were isolated from Phyllanthus urinaria. The structures of these compounds were elucidated by means of spectral techniques including IR, MS, and 1D/2D NMR. 1 and 2 are new compounds.__________Published in Khimiya Prirodnykh Soedinenii, No. 1, pp. 14–17, January–February, 2005.     

Synthesis and Antioxidative Properties of 1,2,3,4-Tetrahydropyridine Derivatives with Different Substituents in 4-Position

Natural products are an excellent source of inspiration for the development of new drugs. Among them, betalains have been extensively studied for their antioxidant properties and potential application as natural food dyes. Herein, we describe the seven-step synthesis of new betalamic acid analogs without carboxy groups in the 2- and 6-position with an overall yield of ~70%. The Folin–Ciocalteu assay was used to determine the antioxidant properties of protected intermediate 21. Additionally, the five-step synthesis of betalamic acid analog 35 with three ester moieties was performed. Using NMR techniques, the stability of the obtained compounds towards oxygen was analyzed.     

Nucleophilic Substitution at Tricoordinate Sulfur—Alkaline Hydrolysis of Optically Active Dialkoxysulfonium Salts: Stereochemistry,Mechanism and Reaction Energetics

Optically active dialkoxyisopropylsulfonium salts were obtained by methylation (ethylation) of optically active alkyl isopropanesulfinates using methyl (ethyl) trifluoromethanesulfonate. Alkaline hydrolysis of a series of methoxy(alkoxy)sulfonium salts afforded the two sulfinate products methyl isopropanesulfinate and alkyl isopropanesulfinate, both formed with a slightly prevailing inversion of configuration at the sulfur atom. DFT calculations revealed that this substitution reaction proceeded stepwise according to an addition-elimination (A–E) mechanism involving the formation of high tetracoordinate S^IV sulfurane intermediates. In addition, the DFT calculations showed that recombination of the hydroxy anion with the methoxy(alkoxy)sulfonium cation—leading to the parallel formation of the two most stable primary sulfuranes, with the hydroxy and alkoxy groups in apical positions and their direct decomposition—is the most energetically favorable pathway.     

Novel α-Aminophosphonates and α-Aminophosphonic Acids: Synthesis,Molecular Docking and Evaluation of Antifungal Activity against Scedosporium Species

The Scedosporium genus is an emerging pathogen with worldwide prevalence and high mortality rates that gives multidrug resistance to antifungals; therefore, pharmacological alternatives must be sought for the treatment of diseases caused by this fungus. In the present project, six new α-aminophosphates were synthesized by the Kabachnik–Fields multicomponent reaction by vortex agitation, and six new monohydrolyzed α-aminophosphonic acids were synthesized by an alkaline hydrolysis reaction. Antifungal activity was evaluated using the agar diffusion method as an initial screening to determine the most active compound compared to voriconazole; then it was evaluated against 23 strains of the genus Scedosporium following the M38-A2 protocol from CLSI (activity range: 648.76–700 µg/mL). Results showed that compound 5f exhibited the highest antifungal activity according to the agar diffusion method (≤1 mg/mL). Cytotoxicity against healthy COS-7 cells was also evaluated by the MTT assay and it was shown that compound 5f exhibits a lower toxicity in comparison to voriconazole at the same concentration (1000 µM). A docking study was conducted afterwards, showing that the possible mechanism of action of the compound is through the inhibition of allosteric 14-α-demethylase. Taking these results as a basis, 5f is presented as a compound with attractive properties for further studies.     

Kinetics and Mechanism Investigation of the Reaction between Triphenylphosphine, Di-tert-butyl Acetylenedicarboxilate and OH-Acid

Kinetic studies were made for the reaction between triphenylphosphine, di‐tert‐butyl acetylenedicarboxilate in the presence of OH‐acid, such as 2‐hydroxy‐4‐methoxybenzaldehyde. To determine the kinetic parameters of the reaction, it was monitored by UV spectrophotometery. The second order fits were automatically drawn by the software associated with a Cary UV spectrophotometer model Bio‐300 at appropriate wavelength. The values of the second order rate constant (k₂) were calculated using standard equations within the program. At the temperature range studied the dependence of the second order rate constant (ln k₂) on reciprocal temperature was in a good agreement with Arrhenius equation. This provided the relevant plots to calculate the activation energy of the reaction. Furthermore useful information was obtained from studies of the effect of solvent and concentration of reactants on the rate of reaction. Proposed mechanism was confirmed according to the obtained results and steady state approximation and first step (k₂) of reaction was recognized as a rate‐determining step on the basis of experimental data. In addition, assignment of more stable isomers (Z or E) was investigated using the theoretical study.     

Straightforward Preparation of (2E,4Z)-2,4-Heptadien-1-ol and (2E,4Z)-2,4-Heptadienal

Abstract

A concise synthesis of (2E,4Z)-2,4-heptadien-1-ol and (2E,4Z)-2,4-heptadienal is presented. Commercially available (Z)-2-penten-1-ol was converted to ethyl-(2E,4Z)-2,4-heptadienoate by reaction with activated MnO₂ and (carboethoxymethylene)triphenylphosphorane in the presence of benzoic acid as a catalyst. Ethyl-(2E,4Z)-2,4-heptadienoate was converted to (2E,4Z)-2,4-heptadien-1-ol with LiAlH₄. The alcohol was partially oxidized to (2E,4Z)-2,4-heptadienal with MnO₂. The title compounds are male-specific, antennally active volatile compounds from the Saltcedar leaf beetle, Diorhabda elongata Brulle (Coleoptera: Chrysomelidae) and have potential use in the biological control of the invasive weed saltcedar (Tamarix spp).     

4-二氰亚甲基-2,6-二甲基-4H-吡喃衍生物的合成及其 荧光效应

两种新的4-二氰亚甲基-2,6-二甲基-4H-吡喃衍生物及对应的聚酰胺酸被合成和表征。该聚酰胺酸在普通有机溶剂中具有良好的可溶性。报道了这些生色团衍生物的光强度、量子产率和发射波长,以及生色团共价键合所形成的聚酰胺酸膜具有比对应的生色团单体更强的荧光效应。     

氨基酸-银反应的光化学特点

氨基酸与银的反应是一个不借外加能量热力学上即可进行的过程,但当引入光之后,可改变反应速率.研究发现:Soret带出现吸收所需光照度的大小顺序为Asp Ag(I)>Thr Ag(I)>Tyr Ag(I)>Lys Ag(I),对于Cys Ag(I)体系,Cys的α羧基氧、α氨基的氮与银(I)结合时光照有利于反应的进行,而S原子与银(I)结合与光照度几无关系.此反应是光助化学反应.     

Interactions of β-Lactoglobulin with Bovine Submaxillary Mucin vs. Porcine Gastric Mucin: The Role of Hydrophobic and Hydrophilic Residues as Studied by Fluorescence Spectroscopy

The aim of this study was to investigate binding interactions between β-lactoglobulin (BLG) and two different mucins, bovine submaxillary mucins (BSM) and porcine gastric mucin (PGM), using intrinsic and extrinsic fluorescence spectroscopies. Intrinsic fluorescence spectra showed an enhanced decrease of fluorescence intensity of BLG at all pH conditions when BLG was mixed with PGM rather than with BSM. We propose that, unlike BSM, the tertiary structure of PGM changes and the hydrophobic regions are exposed at pH 3 due to protonation of negatively charged residues. Results suggest that PGM also facilitated the structural unfolding of BLG and its binding with PGM by a hydrophobic interaction, especially at acidic pH, which was further supported by extrinsic fluorescence spectroscopy. Hydrophobic interaction is suggested as the dominant interaction mechanism between BLG and PGM at pH 3, whereas electrostatic interaction is the dominant one between BLG and BSM.     

(Z,Z)-Selanediylbis(2-propenamides): Novel Class of Organoselenium Compounds with High Glutathione Peroxidase-Like Activity. Regio- and Stereoselective Reaction of Sodium Selenide with 3-Trimethylsilyl-2-propynamides

The efficient regio- and stereoselective synthesis of (Z,Z)-3,3′-selanediylbis(2-propenamides) in 76–93% yields was developed based on the reaction of sodium selenide with 3-trimethylsilyl-2-propynamides. (Z,Z)-3,3′-Selanediylbis(2-propenamides) are a novel class of organoselenium compounds. To date, not a single representative of 3,3′-selanediylbis(2-propenamides) has been described in the literature. Studying glutathione peroxidase-like properties by a model reaction showed that the activity of the obtained products significantly varies depending on the organic moieties in the amide group. Divinyl selenide, which contains two lipophilic cyclohexyl substituents in the amide group, exhibits very high glutathione peroxidase-like activity and this compound is considerably superior to other products in this respect.     

Cooperation of σ–π and σ*–π* Conjugation in the UV/Vis and Fluorescence Spectra of 9,10-Disilylanthracene

In 1996, we reported that silyl groups of 9,10-disilylanthracenes significantly affect the UV/Vis and fluorescence spectra. Although the results indicate that the silyl groups have strong electronic effects on anthracene, the details of the mechanisms responsible for this have not yet been clarified. This article describes the analysis of the UV/Vis and fluorescence spectra of 9,10-bis(diisopropylsilyl)anthracene by theoretical calculations. This study reveals that π conjugation of anthracene is extended by cooperation of σ–π and σ*–π* conjugation between the silyl groups and anthracene. This effect increases the transition moment of the π–π* transition of anthracene. As a result, the molecular extinction coefficient of the ¹L_a band and the fluorescence quantum yield are increased.     

Synthesis of (−)‐Pinellic Acid and Its (9R,12S,13S)‐Diastereoisomer

The total synthesis of (?)‐pinellic acid with (9S,12S,13S)‐configuration and its (9R,12S,13S)‐diastereoisomer was achieved in high overall yields from a common intermediate derived from (+)‐L ‐diethyl tartrate.     

The Theoretical and Experimental Investigation of the Fluorinated Palladium β-Diketonate Derivatives: Structure and Physicochemical Properties

To search for new suitable Pd precursors for MOCVD/ALD processes, the extended series of fluorinated palladium complexes [Pd(CH₃CXCHCO(R))₂] with β-diketone [tfa−1,1,1-trifluoro-2,4-pentanedionato (1); pfpa−5,5,6,6,6-pentafluoro-2,4-hexanedionato (3); hfba−5,5,6,6,7,7,7-heptafluoro-2,4-heptanedionato (5)] and β-iminoketone [i-tfa−1,1,1-trifluoro-2-imino-4-pentanonato (2); i-pfpa−5,5,6,6,6-pentafluoro-2-imino-4-hexanonato (4); i-hfba-5,5,6,6,7,7,7-heptafluoro-2-imino-4-heptanonato (6)] ligands were synthesized with 70–80% yields and characterized by a set of experimental (SXRD, XRD, IR, NMR spectroscopy, TG) and theoretical (DFT, Hirshfeld surface analysis) methods. Solutions of Pd β-diketonates contained both cis and trans isomers, while only trans isomers were detected in the solutions of Pd β-iminoketonates. The molecules 2–6 and new polymorphs of complexes 3 and 5 were arranged preferentially in stacks, and the distance between molecules in the stack generally increased with elongation of the fluorine chain in ligands. The H…F contacts were the main ones involved in the formation of packages of molecules 1–2, and C…F, F…F, NH…F contacts appeared in the structures of complexes 4–6. The stability of complexes and their polymorphs in the crystal phases were estimated from DFT calculations. The TG data showed that the volatility differences between Pd β-iminoketonates and Pd β-diketonates were minimized with the elongation of the fluorine chain in the ligands.     

NMR spectroscopic and theoretical study on the isomerism of dimethyl benzodiazepine(diylidene)diacetates

The isomerism of dimethyl 2,2′-(7,8-dichloro-1H-benzo[b][1,4]diazepine-2,4-(3H,5H)diylidene)diacetate ( 1a ) and dimethyl 2,2′-(7,8-dichloro-3-methyl-1H-benzo[b][1,4]diazepine-2,4-(3H,5H)diylidene)diacetate ( 1b ) was investigated by ¹H, ¹³C and ¹⁵N nuclear magnetic resonance (NMR) spectroscopy. In CDCl₃ solution, inversion of the diazepine ring was observed, whereas in (D₆)DMSO and (D₇)DMF solution, besides the ring inversion, a partial cleavage of one chelate ring appeared connected with (E/Z) isomerization about one of the exocyclic C=C bonds. Gibbs free energies (ΔG) and free activation energies (ΔG^≠) were calculated based on B3PW91-SCRF/ZVP DFT computations. Agreement between NMR data and density functional theory (DFT) computations was found.     

Efficient Improvement of Fluorescence Quantum Yield of Fluoreneethynylene‐Based Polymers by Introducing a Perfluoroalkylbenzene Unit to the Polymers

In comparison with poly(9,9‐dialkylfluorene)s widely used in organic optoelectronic devices, poly(9,9‐dialkylfluoreneethynylene)s ( PFEs ) have attracted less attention partly because of their poor fluorescence quantum yield (FQY) in the solid state. In order to improve the FQY, a 1,4‐bis(perfluorohexyl)benzene (BFB) unit was introduced to PFEs , and the results showed that the absolute FQY in the solid state was dependent on the mol‐% of the BFB unit in the copolymers. When mol‐% was 40 and 50%, respectively, the absolute FQY had greatly increased from 4.9% of PFE to 7.8 and 17.4% of the copolymers, respectively. For comparison, a 1,4‐dihexylbenzene (DHB) unit was also introduced to PFE , whereas the obtained copolymer showed the absolute FQY of 3.8%, suggesting that the DHB unit was not suitable for improvement of the FQY of PFEs . Electrochemically, the PFE containing BFB units showed lower reduction potential than that of PFE . All the fluorine‐containing polymers have good thermal stability.

     

Oligoorganogermanes: Interplay between Aryl and Trimethylsilyl Substituents

Derivatives of main group elements containing element–element bonds are characterized by unique properties due to σ-conjugation, which is an attractive subject for investigation. A novel series of digermanes, Ar₃Ge-Ge(SiMe₃)₃, containing aryl (Ar = p-C₆H₄Me (1), p-C₆H₄F (2), C₆F₅ (3)) and trimethylsilyl substituents, was synthesized by the reaction of germyl potassium salt, [(Me₃Si)₃GeK*THF], with triarylchlorogermanes, Ar₃GeCl. The optical and electronic properties of such substituted oligoorganogermanes were investigated spectroscopically by UV/vis absorption spectroscopy and theoretically by DFT calculations. The molecular structures of compounds 1 and 2 were studied by XRD analysis. Conjugation between all structural fragments (Ge-Ge, Ge-Si, Ge-Ar, where Ar is an electron-donating or withdrawing group) was found to affect the properties.