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Sample records for 5-substituted five-membered oxocarbenium

  1. Nucleophilic addition to silyl-protected five-membered ring oxocarbenium ions governed by stereoelectronic effects

    PubMed Central

    Tran, Vi Tuong

    2013-01-01

    A series of fused-bicyclic acetals containing a disiloxane ring was investigated to evaluate the source of selectivity in silyl-protected 2-deoxyribose systems. The disiloxane ring unexpectedly enables the diaxial conformer of the cation to be stabilized by an electronegative atom at C-3. This low energy conformer subsequently undergoes stereoelectronically controlled nucleophilic addition to give substituted tetrahydrofurans with high diastereoselectivity. PMID:23738497

  2. Congenital Hypofibrinogenemia in Five Members of a Family

    PubMed Central

    Hasselback, R.; Marion, Rita B.; Thomas, J. W.

    1963-01-01

    The bleeding tendency in five members of one family with fibrinogen levels ranging from 58 mg. % to 158 mg. % was mild and chiefly related to dental extractions. Abruptio placentae in one patient produced severe bleeding. Reports of menstrual bleeding patterns in patients with defects of hemostatic mechanisms suggest that normal platelets, vascular function and extrinsic and possibly intrinsic coagulation systems, except for fibrinogen, control menstrual blood loss. An autosomal dominant gene with variable penetrance may determine fibrinogen levels. PMID:13960907

  3. Enantioselective, Copper(I)-Catalyzed Alkynylation of Oxocarbenium Ions to Set Diaryl Tetrasubstituted Stereocenters**

    PubMed Central

    Dasgupta, Srimoyee; Rivas, Thomas; Watson, Mary P.

    2016-01-01

    We have developed an enantioselective, copper(I)-catalyzed addition of terminal alkynes to isochroman ketals to set diaryl, tetrasubstituted stereocenters. The success of this reaction relies on identification of a Cu/PyBox catalyst capable of distinguishing the faces of the diaryl-substituted oxocarbenium ion. This challenging transformation enables efficient conversion of readily available, racemic ketals to high-value, enantioenriched isochroman products with fully substituted stereogenic centers. High yields and enantiomeric excesses are observed for various isochroman ketals and an array of alkynes. PMID:26403641

  4. Enantioselective Copper(I)-Catalyzed Alkynylation of Oxocarbenium Ions to Set Diaryl Tetrasubstituted Stereocenters.

    PubMed

    Dasgupta, Srimoyee; Rivas, Thomas; Watson, Mary P

    2015-11-16

    An enantioselective, copper(I)-catalyzed addition of terminal alkynes to isochroman ketals to set diaryl, tetrasubstituted stereocenters has been developed. The success of this reaction relies on identification of a Cu/PyBox catalyst capable of distinguishing the faces of the diaryl-substituted oxocarbenium ion. This challenging transformation enables efficient conversion of readily available, racemic ketals into high-value enantioenriched isochroman products with fully substituted stereogenic centers. High yields and enantiomeric excesses are observed for various isochroman ketals and an array of alkynes. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. In-Depth Assessment of the Palladium-Catalyzed Fluorination of Five-Membered Heteroaryl Bromides

    PubMed Central

    2015-01-01

    A thorough investigation of the challenging Pd-catalyzed fluorination of five-membered heteroaryl bromides is presented. Crystallographic studies and density functional theory (DFT) calculations suggest that the challenging step of this transformation is C–F reductive elimination of five-membered heteroaryl fluorides from Pd(II) complexes. On the basis of these studies, we have found that various heteroaryl bromides bearing phenyl groups in the ortho position can be effectively fluorinated under catalytic conditions. Highly activated 2-bromoazoles, such as 8-bromocaffeine, are also viable substrates for this reaction. PMID:27056379

  6. In-Depth Assessment of the Palladium-Catalyzed Fluorination of Five-Membered Heteroaryl Bromides.

    PubMed

    Milner, Phillip J; Yang, Yang; Buchwald, Stephen L

    2015-10-12

    A thorough investigation of the challenging Pd-catalyzed fluorination of five-membered heteroaryl bromides is presented. Crystallographic studies and density functional theory (DFT) calculations suggest that the challenging step of this transformation is C-F reductive elimination of five-membered heteroaryl fluorides from Pd(II) complexes. On the basis of these studies, we have found that various heteroaryl bromides bearing phenyl groups in the ortho position can be effectively fluorinated under catalytic conditions. Highly activated 2-bromoazoles, such as 8-bromocaffeine, are also viable substrates for this reaction.

  7. Recent advanced in bioactive systems containing pyrazole fused with a five membered heterocycle.

    PubMed

    Raffa, Demetrio; Maggio, Benedetta; Raimondi, Maria Valeria; Cascioferro, Stella; Plescia, Fabiana; Cancemi, Gabriella; Daidone, Giuseppe

    2015-06-05

    In this review we report the recent advances in bioactive system containing pyrazole fused with a five membered heterocycle, covering the time span of the last decade. All of them are represented around the common structure of the pyrazole ring fused with another five membered heterocycle containing the nitrogen, sulfur and oxygen atoms in all their possible combinations. The classification we have used is based in terms of the therapeutic area providing, when possible, some general conclusions on the targets and mechanisms of action as well as the structure-activity relationships of the molecules.

  8. Five-membered ring annelation in [2.2]paracyclophanes by aldol condensation

    PubMed Central

    Narayanan, Swaminathan Vijay; Jones, Peter G

    2014-01-01

    Summary Under basic conditions 4,5,12,13-tetraacetyl[2.2]paracyclophane (9) cyclizes by a double aldol condensation to provide the two aldols 12 and 15 in a 3:7 ratio. The structures of these compounds were obtained from X-ray structural analysis, spectroscopic data, and mechanistic considerations. On acid treatment 12 is dehydrated to a mixture of the condensed five-membered [2.2]paracyclophane derivatives 18–20, whereas 15 yields a mixture of the isomeric cyclopentadienones 21–23. The structures of these elimination products are also deduced from X-ray and spectroscopic data. The sequence presented here constitutes the simplest route so far to cyclophanes carrying an annelated five-membered ring. PMID:25246961

  9. Five-membered ring annelation in [2.2]paracyclophanes by aldol condensation.

    PubMed

    Hopf, Henning; Narayanan, Swaminathan Vijay; Jones, Peter G

    2014-01-01

    Under basic conditions 4,5,12,13-tetraacetyl[2.2]paracyclophane (9) cyclizes by a double aldol condensation to provide the two aldols 12 and 15 in a 3:7 ratio. The structures of these compounds were obtained from X-ray structural analysis, spectroscopic data, and mechanistic considerations. On acid treatment 12 is dehydrated to a mixture of the condensed five-membered [2.2]paracyclophane derivatives 18-20, whereas 15 yields a mixture of the isomeric cyclopentadienones 21-23. The structures of these elimination products are also deduced from X-ray and spectroscopic data. The sequence presented here constitutes the simplest route so far to cyclophanes carrying an annelated five-membered ring.

  10. Cascade Synthesis of Five-Membered Lactones using Biomass-Derived Sugars as Carbon Nucleophiles.

    PubMed

    Yamaguchi, Sho; Matsuo, Takeaki; Motokura, Ken; Miyaji, Akimitsu; Baba, Toshihide

    2016-06-06

    We report the cascade synthesis of five-membered lactones from a biomass-derived triose sugar, 1,3-dihydroxyacetone, and various aldehydes. This achievement provides a new synthetic strategy to generate a wide range of valuable compounds from a single biomass-derived sugar. Among several examined Lewis acid catalysts, homogeneous tin chloride catalysts exhibited the best performance to form carbon-carbon bonds. The scope and limitations of the synthesis of five-membered lactones using aldehyde compounds are investigated. The cascade reaction led to high product selectivity as well as diastereoselectivity, and the mechanism leading to the diastereoselectivity was discussed based on isomerization experiments and density functional theory (DFT) calculations. The present results are expected to support new approaches for the efficient utilization of biomass-derived sugars.

  11. Catalytic iron-mediated triene carbocyclizations: Stereoselective five-membered ring forming carbocyclizations

    SciTech Connect

    Takacs, J.M.; Myoung, Young-Chan; Anderson, L.G.

    1994-11-18

    The full details of investigations into the regiochemistry and stereochemistry of iron-catalyzed carbocylizations of 2,7,9-decatriene derivatives to form five-membered carbocyclic ring systems are described. The roles of the allylic substituent, the alkene geometry, diene substitution, and the influence of resident stereogenic centers incorporated in the tether chain connecting the reacting 1,3-diene and alkene subunits are discussed.

  12. Diels-Alder reactions of five-membered heterocycles containing one heteroatom.

    PubMed

    Ding, Xiaoyuan; Nguyen, Son T; Williams, John D; Peet, Norton P

    2014-12-17

    Diels-Alder reactions of five-membered heterocycles containing one heteroatom with an N-arylmaleimide were studied. Cycloaddition of 2,5-dimethylfuran (4) with 2-(4-methylphenyl)maleimide (3) in toluene at 60 °C gave bicyclic adduct 5. Cycloadditions of 3 with 2,5-dimethylthiophene (11) and 1,2,5-trimethylpyrrole (14) were also studied. Interestingly, the bicyclic compound 5 cleanly rearranged, with loss of water, when treated with p-toluenesulfonic acid in toluene at 80 °C to give 4,7-dimethyl-2-p-tolylisoindoline-1,3-dione (6).

  13. Carbon Dioxide Utilization by the Five-Membered Ring Products of Cyclometalation Reactions

    PubMed Central

    Omae, Iwao

    2016-01-01

    In carbon dioxide utilization by cyclometalated five-membered ring products, the following compounds are used in four types of applications: 1. 2-Phenylpyrazole iridium compounds, pincer phosphine iridium compounds and 2-phenylimidazoline iridium compounds are used as catalysts for both formic acid production from CO2 and H2, and hydrogen production from the formic acid. This formic acid can be a useful agent for H2 production and storage for fuel cell electric vehicles. 2. Other chemicals, e.g., dimethyl carbonate, methane, methanol and CO, are produced with dimethylaminomethylphenyltin compounds, pincer phosphine iridium compounds, pincer phosphine nickel compound and ruthenium carbene compound or 2-phenylpyridine iridium compounds, and phenylbenzothiazole iridium compounds as the catalysts for the reactions with CO2. 3. The five-membered ring intermediates of cyclometalation reactions with the conventional substrates react with carbon dioxide to afford their many types of carboxylic acid derivatives. 4. Carbon dioxide is easily immobilized at room temperature with immobilizing agents such as pincer phosphine nickel compounds, pincer phosphine palladium compounds, pincer N,N-dimethylaminomethyltin compounds and tris(2-pyridylthio)methane zinc compounds. PMID:28503084

  14. Ursane-type nortriterpenes with a five-membered A-ring from Rubus innominatus.

    PubMed

    Chen, Zhenzhong; Tong, Ling; Feng, Yuanli; Wu, Jizhou; Zhao, Xiaoya; Ruan, Hanli; Pi, Huifang; Zhang, Peng

    2015-08-01

    Two nortriterpenes (rubuminatus A and B), which contain a distinctive contracted a five-membered A-ring ursane-type skeleton, and six triterpenes along with 17 known triterpenes were isolated from the roots of Rubus innominatus S. Moore. These structures were determined to be 19α-hydroxy-2-oxo-nor- A(3)-urs-12-en-28-oic acid, 1β,19α-dihydroxy-2-oxo-nor-A(3)-urs-12-en-28-oic acid, 1β,2α,3α,19α-tetrahy droxyurs-12-en-23-formyl-28-oic acid, 1β,2α,3α,19α,23- pentahydroxyurs-11-en-28-oic acid, 1-oxo-siaresinolic acid, 2α,3α-dihydroxyolean-11,13(18)-dien-19β,28-olide, 1β,2α,3α-trihydroxy-19-oxo- 18,19-seco-urs-11,13(18)-dien-28-oic acid, and 2-O-benzoyl alphitolic acid based on extensive spectroscopic analyses. In vitro anti-inflammatory abilities to modulate the production of TNF-α, IL-1β, and IL-6 in LPS-induced RAW 264.7 macrophages of the compounds were determined. Rubuminatus A and B, as well as 1-oxo-siaresinolic acid and 2α,3α-dihydroxyolean-11,13(18)-dien-19β,28-olide, exhibited significant inhibitory effects on these cytokines.

  15. Computational study on fused five membered heterocyclic compounds containing tertiary oxygen

    NASA Astrophysics Data System (ADS)

    Dai, Yujie; Zhang, Tongcun; Piao, Ying'ai; Zhang, Xiuli; Hu, Yanying; Zhang, Liming; Jia, Shiru; He, Huixin

    2017-02-01

    The structure, stability and electronic properties of two fused five membered heterocyclic compounds containing tertiary oxygen have been investigated with quantum chemistry computation. The results show that 3H-4λ3-furo[1,2-a]furan (M1) and 2a1λ4-oxacyclopenta[cd]pentalene (M2) both own three Csbnd O bonds and especially in M2 the three Csbnd O bonds and angles are approximately identical. The two compounds are comparatively stable and M2 with three pentacycles is more stable than compound M1 according to the Csbnd O bond lengths, bond orders, Egap, electronegativity (χ), hardness (η), electrophilicity (ω), and aromaticity indexes. The aromaticity indexes such as NICS(0), NICS(1) and NICS(1)zz show that they both have strong aromaticity. The natural bonding orbital (NBO) analysis shows that oxygen atom takes hybrid orbitals composed of s and p orbital components to form σ(Csbnd O) bonds in compounds M1 and M2. The second order perturbation analysis shows that the occurrence of intramolecular charge transfer within the molecule exists in compound M1.

  16. A novel secondary structure based on fused five-membered rings motif

    PubMed Central

    Dhar, Jesmita; Kishore, Raghuvansh; Chakrabarti, Pinak

    2016-01-01

    An analysis of protein structures indicates the existence of a novel, fused five-membered rings motif, comprising of two residues (i and i + 1), stabilized by interresidue Ni+1–H∙∙∙Ni and intraresidue Ni+1–H∙∙∙O=Ci+1 hydrogen bonds. Fused-rings geometry is the common thread running through many commonly occurring motifs, such as β-turn, β-bulge, Asx-turn, Ser/Thr-turn, Schellman motif, and points to its structural robustness. A location close to the beginning of a β-strand is rather common for the motif. Devoid of side chain, Gly seems to be a key player in this motif, occurring at i, for which the backbone torsion angles cluster at ~(−90°, −10°) and (70°, 20°). The fused-rings structures, distant from each other in sequence, can hydrogen bond with each other, and the two segments aligned to each other in a parallel fashion, give rise to a novel secondary structure, topi, which is quite common in proteins, distinct from two major secondary structures, α-helix and β-sheet. Majority of the peptide segments making topi are identified as aggregation-prone and the residues tend to be conserved among homologous proteins. PMID:27511362

  17. Conformational Transformation of Five-Membered Rings: the Gas Phase Structure of 2-METHYLTETRAHYDROFURAN

    NASA Astrophysics Data System (ADS)

    Van, Vinh; Nguyen, Ha Vinh Lam; Stahl, Wolfgang

    2015-06-01

    2-Methyltetrahydrofuran (2-MeTHF) is a promising environmentally friendly solvent and biofuel component which is derived from renewable resources. Following the principles of Green Chemistry, 2-MeTHF has been evaluated in various fields like organometallics, metathesis, and biosynthesis on the way to more eco-friendly syntheses. Cyclopentane as the prototype of five-membered rings is well-known to exist as twist or envelope structures. However, the conformational analysis of its heterocyclic derivative 2-methyl-tetrahydrothiophene (MTTP) yielded two stable twist conformers and two envelope transition states. Here, we report on the heavy atom r_s structure of the oxygen-analog of MTTP, 2-MeTHF, studied by a combination of molecular beam Fourier transform microwave spectroscopy and quantum chemistry. One conformer of 2-MeTHF was observed and highly accurate molecular parameters were determined using the XIAM program. In addition, all 13C-isotopologues were assigned in natural abundance of 1%. A structural determination based on the r_s positions of all carbon atoms was achieved via Kraitchman's equations. The methyl group in 2-MeTHF undergoes internal rotation and causes A-E splittings of the rotational lines. The barrier was calculated to be 1142 wn at the MP2/6-311++G(d,p) level of theory, which is rather high. Accordingly, narrow A-E splittings could be observed for only a few transitions. However, the barrier height could be fitted while the angles between the internal rotor axis and the principal axes of inertia were taken from the experimental geometry. V. Pace, P. Hoyos, L. Castoldi, P. Domínguez de María, A. R. Alcántara, ChemSusChem 5 (2012), 1369-1379. a) D. F. Aycock, Org. Process Res. Dev. 11 (2007),156-159. b) M. Smoleń, M. Kȩdziorek, K. Grela, Catal. Commun. 44 (2014), 80-84. V. Van, C. Dindic, H.V.L. Nguyen, W. Stahl, ChemPhysChem 16 (2015), 291-294. H. Hartwig, H. Dreizler, Z. Naturforsch. A 51 (1996), 923-932. J. Kraitchman, Am. J. Phys. 21

  18. Soyasaponin Bh, a Triterpene Saponin Containing a Unique Hemiacetal-Functional Five-Membered Ring from Glycine max (Soybeans)

    USDA-ARS?s Scientific Manuscript database

    Soybeans (Glycine max L. Merill) and soy-based food products are major dietary sources of saponins. An oleanane triterpenoid saponin, soyasaponin Bh (1) containing a unique five-membered ring with a hemiacetal functionality together with seven known saponins were isolated from soybeans. Their struct...

  19. Reaction of five-membered zirconacycloallenoids with the strong Lewis acid B(C6F5)3.

    PubMed

    Bender, Georg; Daniliuc, Constantin G; Wibbeling, Birgit; Kehr, Gerald; Erker, Gerhard

    2014-08-28

    Two alkyl and aryl substituted five-membered zirconacycloallenoids underwent a typical σ-alkyl metallocene reaction with B(C6F5)3, namely cleavage of the Zr-C(sp(3)) bond with formation of zwitterionic (η(2)-allenyl)zirconium/alkylborate products. Both products were characterized by X-ray crystal structural analyses.

  20. Prins Cyclization Catalyzed by a Fe(III) /Trimethylsilyl Halide System: The Oxocarbenium Ion Pathway versus the [2+2] Cycloaddition.

    PubMed

    Pérez, Sixto J; Purino, Martín; Miranda, Pedro O; Martín, Víctor S; Fernández, Israel; Padrón, Juan I

    2015-10-19

    The different factors that control the alkene Prins cyclization catalyzed by iron(III) salts have been explored by means of a joint experimental-computational study. The iron(III) salt/trimethylsilyl halide system has proved to be an excellent promoter in the synthesis of crossed all-cis disubstituted tetrahydropyrans, minimizing the formation of products derived from side-chain exchange. In this iron(III)-catalyzed Prins cyclization reaction between homoallylic alcohols and non-activated alkenes, two mechanistic pathways can be envisaged, namely the classical oxocarbenium route and the alternative [2+2] cycloaddition-based pathway. It is found that the [2+2] pathway is disfavored for those alcohols having non-activated and non-substituted alkenes. In these cases, the classical pathway, via the key oxocarbenium ion, is preferred. In addition, the final product distribution strongly depends upon the nature of the substituent adjacent to the hydroxy group in the homoallylic alcohol, which can favor or hamper a side 2-oxonia-Cope rearrangement.

  1. Five-membered heteroaromatic ring fused-pyrimidine derivatives: design, synthesis, and hedgehog signaling pathway inhibition study.

    PubMed

    Zhang, Liandi; Xin, Minhang; Shen, Han; Wen, Jun; Tang, Feng; Tu, Chongxing; Zhao, Xinge; Wei, Ping

    2014-08-01

    A series of novel five-membered heteroaromatic ring fused-pyrimidine derivatives including purines, pyrrolo[2,3-d]pyrimidines, pyrrolo[3,2-d]pyrimidines, thieno[2,3-d]pyrimidines, thieno[3,2-d]pyrimidines and furo[3,2-d]pyrimidines have been identified to be potent inhibitors of hedgehog signaling pathway. The synthesis and SAR of these compounds are described. Among this new series of hedgehog signaling pathway inhibitors, most compounds exhibited significant inhibitory activity compared to vismodegib, indicating that the five-membered heteroaromatic ring fused-pyrimidines stand out as encouraging scaffolds among the currently reported structural skeletons for hedgehog signaling pathway inhibitors, deserving more exploration and further investigation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. A Bulky Biaryl Phosphine Ligand Allows for Palladium-Catalyzed Amidation of Five-Membered Heterocycles as Electrophiles**

    PubMed Central

    Su, Mingjuan; Buchwald, Stephen L.

    2012-01-01

    Palladium-catalyzed amidation of five-membered heterocyclic bromides that contain multiple heteroatoms was achieved for the first time using the Pd/1 catalyst system. This system allows for efficient access to N-arylated imidazoles, pyrazoles, thiazoles, pyrroles, and thiophenes in moderate to excellent yield. Experimental results and DFT calculations point to the need for electron-rich and especially sterically demanding biaryl phosphine ligand to promote these difficult cross-coupling reactions. PMID:22473747

  3. Antimicrobial activity of various 4- and 5-substituted 1-phenylnaphthalenes

    PubMed Central

    Kelley, Cody; Lu, Songfeng; Parhi, Ajit; Kaul, Malvika; Pilch, Daniel S.; LaVoie, Edmond J.

    2014-01-01

    Bacterial cell division occurs in conjunction with the formation of a cytokinetic Z-ring structure comprised of FtsZ subunits. Agents that can disrupt Z-ring formation have the potential, through this unique mechanism, to be effective against several of the newly emerging multi-drug resistant strains of infectious bacteria. 1- and 12-Aryl substituted benzo[c]phenanthridines have been identified as antibacterial agents that could exert their activity by disruption of Z-ring formation. Substituted 4- and 5-amino-1-phenylnaphthalenes represent substructures within the pharmacophore of these benzo[c]phenanthridines. Several 4- and 5-substituted 1-phenylnaphthalenes were synthesized and evaluated for antibacterial activity against Staphylococcus aureus and Enterococcus faecalis. The impact of select compounds on the polymerization dynamics of S. aureus FtsZ was also assessed. PMID:23314053

  4. Two-dimensional character of internal rotation of furfural and other five-member heterocyclic aromatic aldehydes

    NASA Astrophysics Data System (ADS)

    Bataev, Vadim A.; Pupyshev, Vladimir I.; Godunov, Igor A.

    2016-05-01

    The features of nuclear motion corresponding to the rotation of the formyl group (CHO) are studied for the molecules of furfural and some other five-member heterocyclic aromatic aldehydes by the use of MP2/6-311G** quantum chemical approximation. It is demonstrated that the traditional one-dimensional models of internal rotation for the molecules studied have only limited applicability. The reason is the strong kinematic interaction of the rotation of the CHO group and out-of-plane CHO deformation that is realized for the molecules under consideration. The computational procedure based on the two-dimensional approximation is considered for low lying vibrational states as more adequate to the problem.

  5. A new cascade reaction: concurrent construction of six and five membered rings leading to novel fused quinazolinones.

    PubMed

    Kumar, K Siva; Kumar, P Mahesh; Rao, V Sreenivasa; Jafar, Ahamed A; Meda, Chandana Lakshmi T; Kapavarapu, R; Parsa, Kishore V L; Pal, Manojit

    2012-04-21

    A one-pot cascade reaction has been developed leading to the concurrent construction of six and five membered fused N-heterocyclic rings of indazolo[3,2-b]quinazolinones. The methodology involved the reaction of isatoic anhydride, a hydrazine and o-iodo benzaldehyde in the presence of Pd(PPh(3))(4) and BINAP in MeCN. The mechanism of this cascade reaction is discussed. A variety of indazolo[3,2-b]quinazolinone derivatives were prepared by using this methodology in good yields, some of which were tested for their PDE4 inhibitory properties in vitro. The dose response and docking study performed using a representative compound is presented.

  6. Ab initio investigation of the structure and nonlinear optical properties of five-membered heterocycles containing sulfur

    NASA Astrophysics Data System (ADS)

    Spassova, Milena; Enchev, Venelin

    2004-03-01

    An ab initio HF and MP2 study of the static (hyper)polarizabilities of 2,4-substituted imidazoles and thiazoles is presented. The comparison of the two types of five-membered heterocycles suggests, that the exocyclic heteroatoms have much more influence upon the calculated hyperpolarizabilities, than the ring heteroatoms. It has been found, that adding diffuse functions to the 6-31G** basis set and inclusion of the electron correlation result in drastic changes in the second hyperpolarizability. The changes are more pronounced for the structures with larger number of sulfur atoms. A HF/6-31G** investigation of a push-pull system, in which thiorhodanine has been chosen as acceptor fragment shows an enhancement of the molecular polarizabilities with respect to the corresponding typical donor-acceptor NH 2/NO 2 polyene.

  7. New series of aromatic/ five-membered heteroaromatic butanesulfonyl hydrazones as potent biological agents: Synthesis, physicochemical and electronic properties

    NASA Astrophysics Data System (ADS)

    Hamurcu, Fatma; Mamaş, Serhat; Ozdemir, Ummuhan Ozmen; Gündüzalp, Ayla Balaban; Senturk, Ozan Sanlı

    2016-08-01

    The aromatic/five-membered heteroaromatic butanesulfonylhydrazone derivatives; 5-bromosalicylaldehydebutanesulfonylhydrazone(1), 2-hydroxy-1-naphthaldehydebutane sulfonylhydrazone(2), indole-3-carboxaldehydebutanesulfonylhydrazone (3), 2-acetylfuran- carboxyaldehydebutanesulfonylhydrazone(4), 2-acetylthiophenecarboxyaldehydebutane- sulfonylhydrazone(5) and 2-acetyl-5-chlorothiophenecarboxyaldehydebutanesulfonyl hydrazone (6) were synthesized by the reaction of butane sulfonic acid hydrazide with aldehydes/ketones and characterized by using elemental analysis, 1H NMR, 13C NMR and FT-IR technique. Their geometric parameters and electronic properties consist of global reactivity descriptors were also determined by theoretical methods. The electrochemical behavior of the butanesulfonylhydrazones were investigated by using cyclic voltammetry (CV), controlled potential electrolysis and chronoamperometry (CA) techniques. The number of electrons transferred (n), diffusion coefficient (D) and standard heterogeneous rate constants (ks) were determined by electrochemical methods.

  8. Effect of five-membered ring and heteroatom substitution on charge transport properties of perylene discotic derivatives: A theoretical approach

    NASA Astrophysics Data System (ADS)

    Navarro, Amparo; Fernández-Liencres, M. Paz; Peña-Ruiz, Tomás; García, Gregorio; Granadino-Roldán, José M.; Fernández-Gómez, Manuel

    2016-08-01

    Density functional theory calculations were carried out to investigate the evolvement of charge transport properties of a set of new discotic systems as a function of ring and heteroatom (B, Si, S, and Se) substitution on the basic structure of perylene. The replacement of six-membered rings by five-membered rings in the reference compound has shown a prominent effect on the electron reorganization energy that decreases ˜0.2 eV from perylene to the new carbon five-membered ring derivative. Heteroatom substitution with boron also revealed to lower the LUMO energy level and increase the electron affinity, therefore lowering the electron injection barrier compared to perylene. Since the rate of the charge transfer between two molecules in columnar discotic systems is strongly dependent on the orientation of the stacked cores, the total energy and transfer integral of a dimer as a disc is rotated with respect to the other along the stacking axis have been predicted. Aimed at obtaining a more realistic approach to the bulk structure, the molecular geometry of clusters made up of five discs was fully optimized, and charge transfer rate and mobilities were estimated for charge transport along a one dimensional pathway. Heteroatom substitution with selenium yields electron transfer integral values ˜0.3 eV with a relative disc orientation of 25°, which is the preferred angle according to the dimer energy profile. All the results indicate that the tetraselenium-substituted derivative, not synthetized so far, could be a promising candidate among those studied in this work for the fabrication of n-type semiconductors based on columnar discotic liquid crystals materials.

  9. Not all boronic acids with a five-membered cycle induce tremor, neuronal damage and decreased dopamine.

    PubMed

    Pérez-Rodríguez, Maribel; García-Mendoza, Esperanza; Farfán-García, Eunice D; Das, Bhaskar C; Ciprés-Flores, Fabiola J; Trujillo-Ferrara, José G; Tamay-Cach, Feliciano; Soriano-Ursúa, Marvin A

    2017-06-06

    Several striatal toxins can be used to induce motor disruption. One example is MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), whose toxicity is accepted as a murine model of parkinsonism. Recently, 3-Thienylboronic acid (3TB) was found to produce motor disruption and biased neuronal damage to basal ganglia in mice. The aim of this study was to examine the toxic effects of four boronic acids with a close structural relationship to 3TB (all having a five-membered cycle), as well as boric acid and 3TB. These boron-containing compounds were compared to MPTP regarding brain access, morphological disruption of the CNS, and behavioral manifestations of such disruption. Data was collected through acute toxicity evaluations, motor behavior tests, necropsies, determination of neuronal survival by immunohistochemistry, Raman spectroscopic analysis of brain tissue, and HPLC measurement of dopamine in substantia nigra and striatum tissue. Each compound showed a distinct profile for motor disruption. For example, motor activity was not disrupted by boric acid, but was decreased by two boronic acids (caused by a sedative effect). 3TB, 2-Thienyl and 2-furanyl boronic acid gave rise to shaking behavior. The various manifestations generated by these compounds can be linked, in part, to different levels of dopamine (measured by HPLC) and degrees of neuronal damage in the basal ganglia and cerebellum. Clearly, motor disruption is not induced by all boronic acids with a five-membered cycle as substituent. Possible explanations are given for the diverse chemico-morphological changes and degrees of disruption of the motor system, considering the role of boron and the structure-toxicity relationship. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Effect of five-membered ring and heteroatom substitution on charge transport properties of perylene discotic derivatives: A theoretical approach.

    PubMed

    Navarro, Amparo; Fernández-Liencres, M Paz; Peña-Ruiz, Tomás; García, Gregorio; Granadino-Roldán, José M; Fernández-Gómez, Manuel

    2016-08-07

    Density functional theory calculations were carried out to investigate the evolvement of charge transport properties of a set of new discotic systems as a function of ring and heteroatom (B, Si, S, and Se) substitution on the basic structure of perylene. The replacement of six-membered rings by five-membered rings in the reference compound has shown a prominent effect on the electron reorganization energy that decreases ∼0.2 eV from perylene to the new carbon five-membered ring derivative. Heteroatom substitution with boron also revealed to lower the LUMO energy level and increase the electron affinity, therefore lowering the electron injection barrier compared to perylene. Since the rate of the charge transfer between two molecules in columnar discotic systems is strongly dependent on the orientation of the stacked cores, the total energy and transfer integral of a dimer as a disc is rotated with respect to the other along the stacking axis have been predicted. Aimed at obtaining a more realistic approach to the bulk structure, the molecular geometry of clusters made up of five discs was fully optimized, and charge transfer rate and mobilities were estimated for charge transport along a one dimensional pathway. Heteroatom substitution with selenium yields electron transfer integral values ∼0.3 eV with a relative disc orientation of 25°, which is the preferred angle according to the dimer energy profile. All the results indicate that the tetraselenium-substituted derivative, not synthetized so far, could be a promising candidate among those studied in this work for the fabrication of n-type semiconductors based on columnar discotic liquid crystals materials.

  11. SAR studies of novel 5-substituted 2-arylindoles as nonpeptidyl GnRH receptor antagonists.

    PubMed

    Chu, L; Lo, J L; Yang, Y T; Cheng, K; Smith, R G; Fisher, M H; Wyvratt, M J; Goulet, M T

    2001-02-26

    The discovery of the potency-enhancing effect of 5-substitutions on the novel 2-arylindoles as nonpeptidyl GnRH receptor antagonists led to the identification of several analogues with high affinities on the GnRH receptor. The syntheses and SARs of these 5-substituted-2-arylindole analogues are reported.

  12. High Temperature Chemistry of Chlorinated Acenaphthylene. 3C Bay Acetylene Additions and Annealing by Five-Membered Ring Shifts.

    PubMed

    McIntosh, Grant J; Russell, Douglas K

    2015-12-24

    Experimental and theoretical results concerning the growth and isomerization of chlorinated acenaphthylene, C12H8, during the pyrolysis of chlorohydrocarbons are presented here. A fullerene subunit, C12H8, is a useful system to investigate regarding C60 formation. However, direct experimental observation of isomerization and annealing processes in particular are difficult to confirm due to the high symmetry of the parent molecule. Chlorination lowers the symmetry, essentially labeling carbon atoms, allowing growth and isomerization to be followed directly. Pyrolysis of dichloro- and trichloroethylene, and their copyrolyses with trichlorobenzenes, provides an efficient and general source of chlorinated acenaphthylenes in a range of degrees of chlorination and over a number of unique congeners. Analysis of congener yields as a function of reagents employed, guided by DFT/B3LYP/6-311G(d,p) level calculations, strongly suggests that C2 addition across three-carbon bays in naphthalene is a major driver of growth. Additionally, extremely facile five-membered ring shifts are operative, with chlorine promoting isomerization. Theoretical study of C16H10- and C18H10-based congeners indicate that this is a general phenomenon, and with chlorine also favoring internal cyclopentafused rings in addition to increased isomerization rates, this suggests halogen moieties may be an important feature for efficient fullerene growth.

  13. Mechanistic diversity in thermal fragmentation reactions: a computational exploration of CO and CO₂ extrusions from five-membered rings.

    PubMed

    Rzepa, Henry S; Wentrup, Curt

    2013-08-02

    The mechanisms of a variety of thermal pericyclic fragmentation reactions of five-membered heterocyclic rings are subjected to scrutiny at a density functional level by computation of transition state free energy barriers and intrinsic reaction coordinates (IRCs). The preferred computed products generally match those observed in flash vacuum thermolysis experiments. For certain reactions, which also have the highest reaction temperatures and computed barriers, a degree of multireference character to the wave function manifests in an overestimation of the DFT-computed barrier, with a more reasonable barrier obtained by a CASSCF single point energy calculation. Many of the IRCs exhibit "hidden intermediates" along the reaction pathway, but conversely reactions that could be considered to involve the formation of an intermediate nitrene prior to alkyl or aryl migration show no evidence of such an intermediate. Such exploration of the diversity of behavior in a class of compounds using computational methods with interactive presentation of the results within the body of a journal article is suggested as being almost a sine qua non for laboratory-based research on reactive intermediates.

  14. Structural basis for the potent antisickling effect of a novel class of five-membered heterocyclic aldehydic compounds.

    PubMed

    Safo, Martin K; Abdulmalik, Osheiza; Danso-Danquah, Richmond; Burnett, James C; Nokuri, Samuel; Joshi, Gajanan S; Musayev, Faik N; Asakura, Toshio; Abraham, Donald J

    2004-09-09

    Naturally occurring five-membered heterocyclic aldehydes, including 5-hydroxymethyl-2-furfural, increase the oxygen affinity of hemoglobin (Hb) and strongly inhibit the sickling of homozygous sickle red blood (SS) cells. X-ray studies of Hb complexed with these compounds indicate that they form Schiff base adducts in a symmetrical fashion with the N-terminal alphaVal1 nitrogens of Hb. Interestingly, two cocrystal types were isolated during crystallization experiments with deoxygenated Hb (deoxyHb): one crystal type was composed of the low-affinity or tense (T) state Hb quaternary structure; the other crystal type was composed of high-affinity or relaxed state Hb (with a R2 quaternary structure). The R2 crystal appears to be formed as a result of the aldehydes binding to fully or partially ligated Hb in the deoxyHb solution. Repeated attempts to crystallize the compounds with liganded Hb failed, except on rare occasions when very few R state crystals were obtained. Oxygen equilibrium, high performance liquid chromatography (HPLC), antisickling, and X-ray studies suggest that the examined heterocyclic aldehydes may be acting to prevent polymerization of sickle hemoglobin (HbS) by binding to and stabilizing liganded Hb in the form of R2 and/or various relaxed state Hbs, as well as binding to and destabilizing unliganded T state Hb. The proposed mechanism may provide a general model for the antisickling effects of aldehyde containing small molecules that bind to N-terminal alphaVal1 nitrogens of Hb. The examined compounds also represent a new class of potentially therapeutic agents for treating sickle cell disease (SCD).

  15. Surface chemistry of five-membered aromatic ring molecules containing two different heteroatoms on Si(111)-7 x 7.

    PubMed

    Tao, Feng; Bernasek, Steven L

    2007-04-18

    The surface chemistry of three representative aromatic molecules containing two different heteroatoms isoxazole, oxazole, and thiazole on Si(111)-7 x 7 was studied. These molecules exhibit different competition and selectivity for multiple reaction channels with this surface, determined by a combination of molecular electronic and structural factors. Isoxazole is chemically attached to Si(111)-7 x 7 through both dative-bond addition and [4 + 2]-like cycloaddition. Oxazole chemisorbs on Si(111)-7 x 7 through both dative-bond addition and [2 + 2]-like cycloaddition. The kinetically favored [2 + 2]-like cycloadduct at low temperature is thermally converted into the thermodynamically preferred [4 + 2]-like cycloadduct at a temperature higher than 300 K. Thiazole is chemically bound to this surface only through formation of a Si...N dative bond at low temperature. This dative-bonded molecule is thermally converted into a [4 + 2]-like cycloadduct. The reaction channels of the three five-membered aromatic molecules containing two different heteroatoms (isoxazole, oxazole, and thiazole) and of the aromatic molecules containing only one heteroatom (pyridine, pyrrole, furan, and thiophene) are compared and analyzed for a thorough understanding of the reaction mechanisms of various heterocyclic aromatic molecules on this surface. The intrinsic connection between surface reaction mechanism and molecular electronic structure is demonstrated. This includes the distribution of electron density on the molecular ring determined by the geometric arrangement of the heteroatoms, the electronegativity of the heteroatoms, and the electronic contribution of the heteroatoms to formation of aromatic pi conjugation, as well as the molecular polarity.

  16. Schleyer hyperconjugative aromaticity and Diels-Alder reactivity of 5-substituted cyclopentadienes.

    PubMed

    Levandowski, Brian J; Zou, Lufeng; Houk, K N

    2016-01-05

    Schleyer's discovery of hyperconjugative aromaticity and antiaromaticity in 5-substituted cyclopentadienes further expanded our understanding of the pervasive influence of aromaticity. Acceptors induce antiaromatic character by Schleyer's negative hyperconjugative aromaticity, and donors have the opposite effect. We computationally explored the Diels-Alder reactivity of 5-substituted cyclopentadienes with ethylene and maleic anhydride. The predicted billionfold difference in the computed gas phase rate constants at room temperature for the Diels-Alder reactions of 5-substituted cyclopentadienes with ethylene or maleic anhydride results from differences in the transition state distortion energies, which are directly related to the hyperconjugative aromaticity of these molecules. © 2015 Wiley Periodicals, Inc.

  17. Five-membered rings as diazo components in optical data storage devices: an ab initio investigation of the lowest singlet excitation energies

    NASA Astrophysics Data System (ADS)

    Åstrand, Per-Olof; Sommer-Larsen, Peter; Hvilsted, Søren; Ramanujam, P. S.; Bak, Keld L.; Sauer, Stephan P. A.

    2000-07-01

    The two lowest singlet excitation energies of 18 azo dyes have been studied by ab initio quantum-chemical methods within the second-order polarization propagator approximation (SOPPA). Various combinations of five-membered rings (furan, thiophene, pyrrole, oxazole, thiazole, and imidazole) have been investigated as diazo components for a potential use in optical data storage materials. It is found that the diazo compounds with two heterocyclic five-membered rings have π→π ∗ excitation energies corresponding to laser wavelengths in the region 450-500 nm whereas one five-membered ring and a phenyl group as diazo components results in wavelengths in the region 400-435 nm.

  18. Synthesis of SF5-Substituted Tetrapyrroles, Metalloporphyrins, BODIPYs, and Their Dipyrrane Precursors.

    PubMed

    Golf, Hartwig R A; Reissig, Hans-Ulrich; Wiehe, Arno

    2015-05-15

    The synthesis of novel pentafluorosulfanyl (SF5)-substituted A4-type porphyrins, their corresponding Zn(II)- and Pd(II)-metal complexes, A3-, A2B- and AB2-type corroles, BODIPYs, and their dipyrrane precursors was studied utilizing commercially available SF5-substituted aryl aldehydes. In addition, the functionalization of SF5-substituted tetrapyrroles was investigated by applying the concept of the nucleophilic aromatic substitution (S(N)Ar) with alcohols and sodium azide onto the pentafluorophenyl moiety of a trans-A2B2-porphyrin and two corrole derivatives with a mixed substitution pattern involving the SF5 group. This allows a fine-tuning of the properties of these macrocycles through a selective and mild introduction of functional groups, giving access to multifunctionalized SF5-substituted porphyrinoids. As an example, one functionalized corrole was further reacted with an azido-substituted BODIPY via the copper(I)-catalyzed 1,3-dipolar cycloaddition yielding the first corrole-BODIPY heterodimer involving the pentafluorosulfanyl group.

  19. Synthesis of chiral five-membered carbocyclic ring amino acids with an acetal moiety and helical conformations of its homo-chiral homopeptides.

    PubMed

    Koba, Yurie; Hirata, Yoko; Ueda, Atsushi; Oba, Makoto; Doi, Mitsunobu; Demizu, Yosuke; Kurihara, Masaaki; Tanaka, Masakazu

    2016-11-04

    Chiral five-membered carbocyclic ring amino acids bearing various diol acetal moieties were synthesized starting from l-malic acid, and homo-chiral homopeptides composed of cyclic amino acid (S)-Ac5 c(3EG) bearing an ethylene glycol acetal, up to an octapeptide, were prepared. A conformational analysis revealed that (S)-Ac5 c(3EG) homopeptides formed helical structures. (S)-Ac5 c(3EG) homopeptides, up to hexapeptides, formed helical structures without controlling the helical screw direction, while (S)-Ac5 c(3EG) hepta- and octapeptides formed helical structures with a preference for the left-handed (M) helical-screw direction. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 555-562, 2016. © 2015 Wiley Periodicals, Inc.

  20. The Selective Cross-Coupling of Secondary Alkyl Zinc Reagents to Five-Membered-Ring Heterocycles Using Pd-PEPPSI-IHept(Cl).

    PubMed

    Atwater, Bruce; Chandrasoma, Nalin; Mitchell, David; Rodriguez, Michael J; Pompeo, Matthew; Froese, Robert D J; Organ, Michael G

    2015-08-10

    The ability to cross-couple secondary alkyl centers is fraught with a number of problems, including difficult reductive elimination, which often leads to β-hydride elimination. Whereas catalysts have been reported that provide decent selectivity for the expected (non-rearranged) cross-coupled product with aryl or heteroaryl oxidative-addition partners, none have shown reliable selectivity with five-membered-ring heterocycles. In this report, a new, rationally designed catalyst, Pd-PEPPSI-IHept(Cl), is demonstrated to be effective in selective cross-coupling reactions with secondary alkyl reagents across an impressive variety of furans, thiophenes, and benzo-fused derivatives (e.g., indoles, benzofurans), in most instances producing clean products with minimal, if any, migratory insertion for the first time.

  1. Cyclic tetramers of a five-membered palladacycle based on a head-to-tail-linked isocyanate dimer and their reactivity in cyclotrimerization of isocyanates.

    PubMed

    Lee, Seon Gye; Choi, Keun-Young; Kim, Yong-Joo; Park, SuJin; Lee, Soon W

    2015-04-14

    Reactions of [Pd(styrene)(PR3)2], generated from trans-[PdEt2(PR3)2] and styrene, with 2 equiv. of benzyl isocyanate in THF at room-temperature afforded unusual cyclic Pd-tetramers of five-membered rings consisting of organic isocyanate dimers and palladium, [Pd(PR3){-C(O)N(R)C(O)N(R)-}]4 (PR3 = PMe3, ; PR3 = PMe2Ph, ). Additionally, a cyclic trimer, (RNCO)3, (R = benzyl) was produced as a catalytic product. Treatment of the cyclic tetramer () with 4 equiv. of chelated phosphine, such as (1,2-bis(diethylphosphino)ethane) (DEPE) or (1,2-bis(dimethylphosphino)ethane) (DMPE), readily caused conversion to a metallacyclic cis-form, [Pd{N(R)C(O)N(R)C(O)}(P ∼ P)] (P ∼ P = DEPE, ; P ∼ P = DMPE, ) in quantitative yields. In contrast, reactions of Pd(0)-PR3 with 2 equiv. of Ar-NCO (Ar = Ph, p-tolyl, p-ClC6H4) afforded metallacyclic complexes having a dimeric isocyanato moiety, cis-[Pd{C(O)N(Ar)-C(O)N(Ar)}(PR3)2] (PR3 = PMe3 Ar = C6H5, ; p-MeC6H4, ; p-Cl-C6H4, ; PR3 = PMe2Ph, Ar = p-Cl-C6H4, ). Treatment of the palladacyclic complex () with an equimolar amount of chelated phosphine such as DEPE readily caused conversion to a palladacyclic cis-form, [Pd{N(Ar)C(O)N(Ar)C(O)}(DEPE)], in quantitative yield. The catalytic cyclotrimerization of benzyl isocyanate to [Pd(styrene)(PMe3)2] was achieved by varying the molar ratio of R-NCO (R = benzyl). In addition, catalytic cyclotrimerization was performed from the five-membered palladacyclic complexes or the Pd(0)-PR3 complex with excess Ar-NCO.

  2. [Synthesis and antitumor activity of 5-substituted-2-(pyridyl)benzothiazole compounds].

    PubMed

    Liu, Wen-Hu; Chang, Jin-Xia; Liu, Yi

    2013-01-01

    Fifteen novel 5-substituted-2-(pyridyl)benzothiazole compounds were designed and synthesized by simple hydrolization and condensation reaction of the 2-amino-5-substituent benzothiazole. Activities of these synthesized compounds were evaluated on Bcap-37, HCT-15 and HepG2 tumor cells in vitro by standard MTT assay. 5-Fluorouracil (5-FU) was used as the positive control. The results revealed that most of the new compounds had potent effects on Bcap-37, HCT-15 and HepG2 tumor cells, and had no or less effect on 293T and L02 normal cells. Particularly, compounds 1c and 2e exhibited better activities on HCT-15 and HepG2 cells with IC50 values of 41.59 and 38.65 micromol x L(-1), and 1i showed excellent activities on Bcap-37 and HepG2 cells with IC50 values of 46.63 and 23.51 micromol x L(-1), respectively. The structure-activity relationship of 5-substituted-2-(pyridyl)benzothiazole compounds were also discussed preliminarily.

  3. Design, synthesis and evaluation of 5-substituted 1-H-tetrazoles as potent anticonvulsant agents.

    PubMed

    Liao, Ai-Mei; Wang, Tiantian; Cai, Bangrong; Jin, Yi; Cheon, Seunghoon; Chun, ChangJu; Wang, Zengtao

    2017-04-01

    A series of 5-substituted 1-H-tetrazoles were designed and synthesized as potent anticonvulsant agents. Their preliminary anticonvulsant activities were evaluated using maximal electroshock and subcutaneous pentylenetetrazole (scPTZ) seizure tests. Neurotoxicity was determined using rotarod test. The results indicated that the compound 2j in scPTZ model exhibited the ED50 values of 83.3 mg/kg, superior to the standard drug ethosuximide with the maximum activity. In addition, compound 2k showed the most potent activity in MES model with ED50 value of 9.6 mg/kg and TD50 value of 189.5 mg/kg after intraperitoneal injection in mice, and displayed a high protective index (TD50/ED50) of 19.7 compared to reference antiepileptic drugs.

  4. Synthesis and Bioactivity of 5-Substituted-2-furoyl Diacylhydazide Derivatives with Aliphatic Chain

    PubMed Central

    Cui, Zining; Li, Xinghai; Tian, Fang; Yan, Xiaojing

    2014-01-01

    A series of 5-substituted-2-furoyl diacylhydazide derivatives with aliphatic chain were designed and synthesized. Their structures were characterized by IR, 1H NMR, elemental analysis, and X-ray single crystal diffraction. The anti-tumor bioassay revealed that some title compounds exhibited promising activity against the selected cancer cell lines, especially against the human promyelocytic leukemic cells (HL-60). Their fungicidal tests indicated that most of the title compounds showed significant anti-fungal activity. The preliminary structure-activity relationship showed that the aliphatic chain length and differences in the R2 group had obvious effects on the anti-tumor and anti-fungal activities. The bioassay results demonstrated that the title compounds hold great promise as novel lead compounds for further drug discovery. PMID:24853128

  5. Transferable potentials for phase equilibria. 9. Explicit hydrogen description of benzene and five-membered and six-membered heterocyclic aromatic compounds.

    PubMed

    Rai, Neeraj; Siepmann, J Ilja

    2007-09-13

    The explicit hydrogen version of the transferable potentials for phase equilibria (TraPPE-EH) force field is extended to benzene, pyridine, pyrimidine, pyrazine, pyridazine, thiophene, furan, pyrrole, thiazole, oxazole, isoxazole, imidazole, and pyrazole. While the Lennard-Jones parameters for carbon, hydrogen (two types), nitrogen (two types), oxygen, and sulfur are transferable for all 13 compounds, the partial charges are specific for each compound. The benzene dimer energies for sandwich, T-shape, and parallel-displaced configurations obtained for the TraPPE-EH force field compare favorably with high-level electronic structure calculations. Gibbs ensemble Monte Carlo simulations were carried out to compute the single-component vapor-liquid equilibria for benzene, pyridine, three diazenes, and eight five-membered heterocycles. The agreement with experimental data is excellent with the liquid densities and vapor pressures reproduced within 1 and 5%, respectively. The critical temperatures and normal boiling points are predicted with mean deviations of 0.8 and 1.6%, respectively.

  6. Influence of fused aromatic ring on the stability of charge transfer complex between iodine and some five membered heterocyclic molecules through ultrasonic and spectral studies

    NASA Astrophysics Data System (ADS)

    Ulagendran, V.; Balu, P.; Kannappan, V.; Kumar, R.; Jayakumar, S.

    2017-08-01

    The charge transfer (CT) interaction between two fused heterocyclic compounds with basic pyrrole group as donors, viz., indole (IND) and carbazole (CAR), and iodine (acceptor) in DMSO medium is investigated by ultrasonic and UV-visible spectral methods at 303 K. The formation of CT complex in these systems is established from the trend in acoustical and excess thermo acoustical properties with molar concentration. The frequency acoustic spectra (FAS) is also carried out on these two systems for two fixed concentrations 0.002 M and 0.02 M, and in the frequency range 1 MHz-10 MHz to justify the frequency chosen for ultrasonic study. The absorption coefficient values in solution are computed and discussed. The formation constants of these complexes are determined using Kannappan equation in ultrasonic method. The formation of 1:1 complexes between iodine and IND, CAR was established by the theory of Benesi - Hildebrand in the UV-visible spectroscopic method. The stability constants of the CT complexes determined by spectroscopic and ultrasonic methods show a similar trend. These values also indicate that the presence of fused aromatic ring influences significantly when compared with K values of similar CT complexes of parent five membered heterocyclic compound (pyrrole) reported by us earlier.

  7. Minimization of the Thiolactomycin Biosynthetic Pathway Reveals that the Cytochrome P450 Enzyme TlmF Is Required for Five-Membered Thiolactone Ring Formation.

    PubMed

    Tang, Xiaoyu; Li, Jie; Moore, Bradley S

    2017-06-19

    Thiolactomycin (TLM) belongs to a class of rare and unique thiotetronate antibiotics that inhibit bacterial fatty acid synthesis. Although this group of natural product antibiotics was first discovered over 30 years ago, the study of TLM biosynthesis remains in its infancy. We recently discovered the biosynthetic gene cluster (BGC) for TLM from the marine bacterium Salinispora pacifica CNS-863. Here, we report the investigation of TLM biosynthetic logic through mutagenesis and comparative metabolic analyses. Our results revealed that only four genes (tlmF, tlmG, tlmH, and tlmI) are required for the construction of the characteristic γ-thiolactone skeleton of this class of antibiotics. We further showed that the cytochrome P450 TlmF does not directly participate in sulfur insertion and C-S bond formation chemistry but rather in the construction of the five-membered thiolactone ring as, upon its deletion, we observed the alternative production of the six-membered δ-thiolactomycin. Our findings pave the way for future biochemical investigation of the biosynthesis of this structurally unique group of thiotetronic acid natural products. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Cytogenetic and symbiont analysis of five members of the B. dorsalis complex (Diptera, Tephritidae): no evidence of chromosomal or symbiont-based speciation events

    PubMed Central

    Augustinos, Antonios A.; Drosopoulou, Elena; Gariou-Papalexiou, Aggeliki; Asimakis, Elias D.; Cáceres, Carlos; Tsiamis, George; Bourtzis, Kostas; Penelope Mavragani-Tsipidou; Zacharopoulou, Antigone

    2015-01-01

    Abstract The Bactrocera dorsalis species complex, currently comprising about 90 entities has received much attention. During the last decades, considerable effort has been devoted to delimiting the species of the complex. This information is of great importance for agriculture and world trade, since the complex harbours several pest species of major economic importance and other species that could evolve into global threats. Speciation in Diptera is usually accompanied by chromosomal rearrangements, particularly inversions that are assumed to reduce/eliminate gene flow. Other candidates currently receiving much attention regarding their possible involvement in speciation are reproductive symbionts, such as Wolbachia, Spiroplasma, Arsenophonus, Rickettsia and Cardinium. Such symbionts tend to spread quickly through natural populations and can cause a variety of phenotypes that promote pre-mating and/or post-mating isolation and, in addition, can affect the biology, physiology, ecology and evolution of their insect hosts in various ways. Considering all these aspects, we present: (a) a summary of the recently gained knowledge on the cytogenetics of five members of the Bactrocera dorsalis complex, namely Bactrocera dorsalis s.s., Bactrocera invadens, Bactrocera philippinensis, Bactrocera papayae and Bactrocera carambolae, supplemented by additional data from a Bactrocera dorsalis s.s. colony from China, as well as by a cytogenetic comparison between the dorsalis complex and the genetically close species, Bactrocera tryoni, and, (b) a reproductive symbiont screening of 18 different colonized populations of these five taxa. Our analysis did not reveal any chromosomal rearrangements that could differentiate among them. Moreover, screening for reproductive symbionts was negative for all colonies derived from different geographic origins and/or hosts. There are many different factors that can lead to speciation, and our data do not support chromosomal and/or symbiotic

  9. Cytogenetic and symbiont analysis of five members of the B. dorsalis complex (Diptera, Tephritidae): no evidence of chromosomal or symbiont-based speciation events.

    PubMed

    Augustinos, Antonios A; Drosopoulou, Elena; Gariou-Papalexiou, Aggeliki; Asimakis, Elias D; Cáceres, Carlos; Tsiamis, George; Bourtzis, Kostas; Penelope Mavragani-Tsipidou; Zacharopoulou, Antigone

    2015-01-01

    The Bactrocera dorsalis species complex, currently comprising about 90 entities has received much attention. During the last decades, considerable effort has been devoted to delimiting the species of the complex. This information is of great importance for agriculture and world trade, since the complex harbours several pest species of major economic importance and other species that could evolve into global threats. Speciation in Diptera is usually accompanied by chromosomal rearrangements, particularly inversions that are assumed to reduce/eliminate gene flow. Other candidates currently receiving much attention regarding their possible involvement in speciation are reproductive symbionts, such as Wolbachia, Spiroplasma, Arsenophonus, Rickettsia and Cardinium. Such symbionts tend to spread quickly through natural populations and can cause a variety of phenotypes that promote pre-mating and/or post-mating isolation and, in addition, can affect the biology, physiology, ecology and evolution of their insect hosts in various ways. Considering all these aspects, we present: (a) a summary of the recently gained knowledge on the cytogenetics of five members of the Bactrocera dorsalis complex, namely Bactrocera dorsalis s.s., Bactrocera invadens, Bactrocera philippinensis, Bactrocera papayae and Bactrocera carambolae, supplemented by additional data from a Bactrocera dorsalis s.s. colony from China, as well as by a cytogenetic comparison between the dorsalis complex and the genetically close species, Bactrocera tryoni, and, (b) a reproductive symbiont screening of 18 different colonized populations of these five taxa. Our analysis did not reveal any chromosomal rearrangements that could differentiate among them. Moreover, screening for reproductive symbionts was negative for all colonies derived from different geographic origins and/or hosts. There are many different factors that can lead to speciation, and our data do not support chromosomal and/or symbiotic

  10. A rearrangement of 1,1-linked four-membered rings to bicyclic bridgehead five-membered rings: a phosphorus turn.

    PubMed

    Ionkin, Alex S; Marshall, William J; Fish, Brian M

    2009-12-21

    Novel rearrangements of 2,3,2',3'-tetra-tert-butyl-4,4'-bis-trimethylsilanyloxy-1,2,1',2'-tetrahydro-[1,1']biphosphetyl (7) to 1,2,5,6-tetra-tert-butyl-3,7-bis-trimethylsilanyloxy-1H,5H-[1,2]diphospholo-[1,2-a][1,2]diphosphole (9) and of 3,4,3,4-tetra-tert-butyl-[1,1']biphosphetanyl-2,2'-dione (10) to 2,3,6,7-tetra-tert-butyl-tetrahydro-[1,2]diphospholo[1,2-a][1,2]diphosphole-1,5-dione (12) were observed during sublimation at 150 degrees C in 0.1 mm vacuum. The C-P-C internal angles of the four-membered rings, which reflect steric strain in (7), were 71.9(2) degrees and 77.9(1) degrees; the C-P-P internal angles of the five-membered rings of 9 were 90.88(6) degrees and 93.02(6) degrees after rearrangement. Reaction of 7 with metallic caesium provided the caesium salt of 3,4-di-tert-butyl-3,4-dihydro-phosphet-2-ol (15), which is the first example of a 2lambda-3-phospha-1-enolate being incorporated into four-membered ring. Due to its large size, the caesium cation has a rare coordination mode with both the phosphorus and oxygen atoms of the 2lambda-3-phospha-1-enolate, forming infinite polymeric chains in the solid state of 15. Two tert-butyl groups in the vicinal positions of compounds 7, 9, 10, 12 and 15 dictate the gauche conformations in compounds 7, 9, 10, 12 and 15, enforcing this stereoselectivity around the C-C-C portion of the rings in the enlargement reaction.

  11. Growth of epitaxial orthorhombic YO1.5-substituted HfO2 thin film

    NASA Astrophysics Data System (ADS)

    Shimizu, Takao; Katayama, Kiliha; Kiguchi, Takanori; Akama, Akihiro; Konno, Toyohiko J.; Funakubo, Hiroshi

    2015-07-01

    YO1.5-substituted HfO2 thin films with various substitution amounts were grown on (100) YSZ substrates by the pulsed laser deposition method directly from the vapor phase. The epitaxial growth of film with different YO1.5 amounts was confirmed by the X-ray diffraction method. Wide-area reciprocal lattice mapping measurements were performed to clarify the crystal symmetry of films. The formed phases changed from low-symmetry monoclinic baddeleyite to high-symmetry tetragonal/cubic fluorite phases through an orthorhombic phase as the YO1.5 amount increased from 0 to 0.15. The additional annular bright-field scanning transmission electron microscopy indicates that the orthorhombic phase has polar structure. This means that the direct growth by vapor is of polar orthorhombic HfO2-based film. Moreover, high-temperature X-ray diffraction measurements showed that the film with a YO1.5 amount of 0.07 with orthorhombic structure at room temperature only exhibited a structural phase transition to tetragonal phase above 450 °C. This temperature is much higher than the reported maximum temperature of 200 °C to obtain ferroelectricity as well as the expected temperature for real device application. The growth of epitaxial orthorhombic HfO2-based film helps clarify the nature of ferroelectricity in HfO2-based films (186 words/200 words).

  12. Functional diversity among 5-substituted nicotine analogs; in vitro and in vivo investigations.

    PubMed

    Dukat, Małgorzata; Damaj, Imad M; Young, Richard; Vann, Robert; Collins, Allan C; Marks, Michael J; Martin, Billy R; Glennon, Richard A

    2002-01-25

    Two 5-substituted derivatives of nicotine (nicotinic acetylcholine receptor: K(i)=2.4 nM) were synthesized and evaluated: 5-bromonicotine (K(i)=6.9 nM) and 5-methoxynicotine (K(i)=14.3 nM). Despite their high affinity, neither 5-bromonicotine nor 5-methoxynicotine mimicked nicotine in producing antinociceptive (tail-flick, hotplate), hypolocomotor, or hypothermic effects in mice. Neither agent antagonized the hypolocomotor actions of nicotine, whereas 5-methoxynicotine, but not 5-bromonicotine, antagonized the antinociceptive (tail-flick) activity of nicotine in a dose-related manner. In tests of stimulus generalization using rats trained to discriminate 0.6 mg/kg of (-)-nicotine from vehicle, 5-bromonicotine substituted for nicotine. Further evaluation of 5-bromonicotine indicated that it might be a partial agonist at alpha4beta2 receptors (stimulation of Rb(+) efflux; alpha4beta2 receptors expressed in oocytes) and at alpha3-containing nicotinic acetylcholine receptors (synaptosomal dopamine release). Thus, 5-bromonicotine might be acting as a partial agonist at alpha4beta2 receptors and/or some of its effects might be related to interactions with non-alpha4beta2 receptors. Clearly, the effects of 5-bromonicotine and 5-methoxynicotine are different from those of nicotine, and from one another. These actions demonstrate that substitution at the 5-position of nicotine exerts a profound influence on the pharmacological profile as well as agonist/antagonist properties of nicotine.

  13. Novel 5-substituted benzyloxy-2-arylbenzofuran-3-carboxylic acids as calcium activated chloride channel inhibitors

    PubMed Central

    Kumar, Satish; Namkung, Wan; Verkman, A. S.; Sharma, Pawan K.

    2013-01-01

    Transmembrane protein 16A (TMEM16A) channels are recently discovered membrane proteins that functions as a calcium activated chloride channel (CaCC). CaCCs are major regulators of various physiological processes, such as sensory transduction, epithelial secretion, smooth muscle contraction and oocyte fertilization. Thirty novel 5-substituted benzyloxy-2-arylbenzofuran-3-carboxylic acids (B01–B30) were synthesized and evaluated for their TMEM16A inhibitory activity by using short circuit current measurements in Fischer rat thyroid (FRT) cells expressing human TMEM16A. IC50 values were calculated using YFP fluorescence plate reader assay. Final compounds, having free carboxylic group displayed significant inhibition. Eight of the novel compounds B02, B13, B21, B23, B25, B27, B28, B29 exhibit excellent CaCCs inhibition with IC50 value <6 μM, with compound B25 exhibiting the lowest IC50 value of 2.8 ± 1.3 μM. None of the tested ester analogs of final benzofuran derivatives displayed TMEM16A/CaCCs inhibition. PMID:22739085

  14. Design and studies of novel 5-substituted alkynylpyrimidine nucleosides as potent inhibitors of mycobacteria.

    PubMed

    Rai, Dinesh; Johar, Monika; Manning, Tracey; Agrawal, B; Kunimoto, Dennis Y; Kumar, Rakesh

    2005-11-03

    We herein report a new category of 5-substituted pyrimidine nucleosides as potent inhibitors of mycobacteria. A series of 5-alkynyl derivatives of 2'-deoxyuridine (1-8), 2'-deoxycytidine (9-14), uridine (15-17), and 2'-O-methyluridine (18, 19) were synthesized and evaluated for their antimycobacterial activity in vitro. 5-Decynyl, 5-dodecynyl, and 5-tetradecynyl derivatives showed the highest antimycobacterial potency against M. bovis and M. avium, with the 2'-deoxyribose derivatives being more effective than the ribose analogues. Nucleosides bearing short alkynyl side chains 5-ethynyl, 5-propynyl, 5-pentynyl, and 5-heptynyl were mostly not inhibitory. Incorporation of a phenylethynyl function at the 5-position diminished the antimicrobial effect. Furthermore, related bicyclic analogues (20-24) were devoid of antimycobacterial activity, indicating that an acyclic side chain at the C-5 position of the pyrimidine ring is essential for potent activity. Compounds 1-17 were synthesized by the Pd-catalyzed coupling reactions of respective alkynes with 5-iodo derivatives of 2'-deoxyuridine, 2'-deoxycytidine, and uridine. Intramolecular cyclization of 1 and 3-6 in the presence of Cu afforded the corresponding bicyclic compounds 20-24. The investigated nucleosides are recognized here for the first time to be potent inhibitors of mycobacteria. This class of compounds could be of interest for lead optimization as antimycobacterial agents.

  15. Study of the antimetabolite properties of anomeric 5-substituted 2'-deoxyuridines

    SciTech Connect

    Nedorezova, T.P.; Potapova, G.I.; Mel'nik, S.Ya.; Preobrazhenskaya, M.N.

    1987-04-01

    The authors study the influence of anomeric 5-substituted 2'-dioxyuridines compounds I-XIV on the incorporation of labeled precursors into the DNA of ascites hepatoma 22A cells of C3HA mice in vitro and in vivo. In addition, the DNA of chicken fibroblasts, growing in a monolayer, before and after infection with herpes simplex virus was studied. The influence of the given compounds I-XIV on the activity of thymidine and deoxycytidine kinases and pyrimidine nucleoside phosphorylases, isolated and partially purified from tumor cells of animals and humans was also investigated. In some of the experiments, radioactive precursors /sup 14/C-dThd and /sup 3/H-dCyd or (/sup 3/H)deoxyuridine were injected. The kinetics of the competitive phosphorylation of /sup 14/C-dThd in the presence of antiherpetic nucleosides and the phosphorylation of these compounds with gamma-/sup 32/P-ATP as the second substrate of the reaction were studied.

  16. Synthesis, Structural Characterization, and Field-Effect Transistor Properties of n-Channel Semiconducting Polymers Containing Five-Membered Heterocyclic Acceptors: Superiority of Thiadiazole Compared with Oxadiazole.

    PubMed

    Chen, Huajie; Liu, Zhaoxia; Zhao, Zhiyuan; Zheng, Liping; Tan, Songting; Yin, Zhihong; Zhu, Chunguang; Liu, Yunqi

    2016-12-07

    Five-membered 1,3,4-oxadiazole (OZ) and 1,3,4-thiadiazole (TZ) heterocycle-based copolymers as active layer have long been ignored in solution-processable n-channel polymer field-effect transistors (PFETs) despite the long history of using OZ or TZ derivatives as the electron-injecting materials in organic light-emitting devices and their favorable electron affinities. Herein, we first report the synthesis and PFETs performance of two n-channel conjugated polymers bearing OZ- or TZ-based acceptor moieties, i.e., PNOZ and PNTZ, where simple thiophene units are utilized as the weak donors and additional alkylated-naphthalenediimides units are used as the second acceptors. A comparative study has been performed to reveal the effect of different heterocyclic acceptors on thermal properties, electronic properties, ordering structures, and carrier transport performance of the target polymers. It is found that both polymers possess low-lying LUMO values below -4.0 eV, indicating high electron affinity for both heterocycle-based polymers. Because of strong polarizable ability of sulfur atom in TZ heterocycle, PNTZ exhibits a red shift in maximal absorption and stronger molecular aggregation even in the diluted chlorobenzene solution as compared to the OZ-containing PNOZ. Surface morphological study reveals that a nodule-like surface with a rough surface morphology is observed clearly for PNOZ films, whereas PNTZ films display highly uniform surface morphology with well interconnected fiber-like polycrystalline grains. Investigation of PFETs performance indicates that both polymers afford air-stable n-channel transport characteristics. The uniform morphological structure and compact π-π stacking endow PNTZ with a high electron mobility of 0.36 cm(2) V(-1) s(-1), much higher than that of PNOZ (0.026 cm(2) V(-1) s(-1)). These results manifest the feasibility in improving electron-transporting property simply by tuning heteroatom substitutes in n-channel polymers; further

  17. 5-Substituted-benzylsulfanyl-thiophene-2-sulfonamides with effective carbonic anhydrase inhibitory activity: Solution and crystallographic investigations.

    PubMed

    Ivanova, Jekaterīna; Balode, Agnese; Žalubovskis, Raivis; Leitans, Janis; Kazaks, Andris; Vullo, Daniela; Tars, Kaspars; Supuran, Claudiu T

    2017-02-01

    A series of 5-substituted-benzylsulfanyl-thiophene-2-sulfonamides was prepared by reacting 5-bromo-thiophene-2-sulfonamide with 5-substituted-benzyl mercaptans. The new compounds were investigated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. The cytosolic human (h) isoforms hCA I was poorly inhibited by the new sulfonamides (KIs in the range of 683-4250nM), whereas hCA II, and the transmembrane, tumor associated isoforms hCA IX and XII were effectively inhibited in the subnanomolar-nanomolar range. A high resolution X-ray crystal structure of the adduct of hCA II with one of the new sulfonamides allowed us to rationalize the excellent inhibitory activity of these heterocyclic sulfonamides. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Improved Synthesis of 5-Substituted 1H-Tetrazoles via the [3+2] Cycloaddition of Nitriles and Sodium Azide Catalyzed by Silica Sulfuric Acid

    PubMed Central

    Du, Zhenting; Si, Changmei; Li, Youqiang; Wang, Yin; Lu, Jing

    2012-01-01

    A silica supported sulfuric acid catalyzed [3+2] cycloaddition of nitriles and sodium azide to form 5-substituted 1H-tetrazoles is described. The protocol can provide a series of 5-substituted 1H-tetrazoles using silica sulfuric acid from nitriles and sodium azide in DMF in 72%–95% yield. PMID:22606004

  19. Improved synthesis of 5-substituted 1H-tetrazoles via the [3+2] cycloaddition of nitriles and sodium azide catalyzed by silica sulfuric acid.

    PubMed

    Du, Zhenting; Si, Changmei; Li, Youqiang; Wang, Yin; Lu, Jing

    2012-01-01

    A silica supported sulfuric acid catalyzed [3+2] cycloaddition of nitriles and sodium azide to form 5-substituted 1H-tetrazoles is described. The protocol can provide a series of 5-substituted 1H-tetrazoles using silica sulfuric acid from nitriles and sodium azide in DMF in 72%-95% yield.

  20. An efficient approach for conversion of 5-substituted 2-thiouridines built in RNA oligomers into corresponding desulfured 4-pyrimidinone products.

    PubMed

    Chwialkowska, Anna; Wielgus, Ewelina; Leszczynska, Grazyna; Sobczak, Milena; Mikolajczyk, Barbara; Sochacka, Elzbieta; Nawrot, Barbara

    2015-08-15

    An efficient approach for the desulfuration of C5-substituted 2-thiouridines (R5S2U) bound in the RNA chain exclusively to 4-pyrimidinone nucleoside (R5H2U)-containing RNA products is proposed. This post-synthetic transformation avoids the preparation of a suitably protected H2U phosphoramidite, which otherwise would be necessary for solid-phase synthesis of the modified RNA. Optimization of the desulfuration, which included reaction stoichiometry, time and temperature, allowed to transform a set of ten R5S2U-RNAs into their R5H2U-RNA congeners in ca. 90% yield.

  1. Prebiotic synthesis of 5-substituted uracils: a bridge between the RNA world and the DNA-protein world

    NASA Technical Reports Server (NTRS)

    Robertson, M. P.; Miller, S. L.

    1995-01-01

    Under prebiotic conditions, formaldehyde adds to uracil at the C-5 position to produce 5-hydroxymethyluracil with favorable rates and equilibria. Hydroxymethyluracil adds a variety of nucleophiles, such as ammonia, glycine, guanidine, hydrogen sulfide, hydrogen cyanide, imidazole, indole, and phenol, to give 5-substituted uracils with the side chains of most of the 20 amino acids in proteins. These reactions are sufficiently robust that, if uracil had been present on the primitive Earth, then these substituted uracils would also have been present. The ribozymes of the RNA world would have included many of the functional groups found in proteins today, and their catalytic activities may have been considerably greater than presently assumed.

  2. Prebiotic synthesis of 5-substituted uracils: a bridge between the RNA world and the DNA-protein world

    NASA Technical Reports Server (NTRS)

    Robertson, M. P.; Miller, S. L.

    1995-01-01

    Under prebiotic conditions, formaldehyde adds to uracil at the C-5 position to produce 5-hydroxymethyluracil with favorable rates and equilibria. Hydroxymethyluracil adds a variety of nucleophiles, such as ammonia, glycine, guanidine, hydrogen sulfide, hydrogen cyanide, imidazole, indole, and phenol, to give 5-substituted uracils with the side chains of most of the 20 amino acids in proteins. These reactions are sufficiently robust that, if uracil had been present on the primitive Earth, then these substituted uracils would also have been present. The ribozymes of the RNA world would have included many of the functional groups found in proteins today, and their catalytic activities may have been considerably greater than presently assumed.

  3. 2-Trimethylsilylethanesulfonyl (SES) versus tosyl (Ts) protecting group in the preparation of nitrogen-containing five-membered rings. A novel route for the synthesis of substituted pyrrolines and pyrrolidines.

    PubMed

    Declerck, Valérie; Allouchi, Hassan; Martinez, Jean; Lamaty, Frédéric

    2007-02-16

    The 2-trimethylsilylethanesulfonyl (or SES) protecting group was compared to the tosyl (Ts) group in the preparation of a nitrogen-containing five-membered ring obtained by the aza-Baylis-Hillman/alkylation/RCM route. While deprotection of Ts-protected pyrrolines gave only pyrroles, deprotection of the same SES-protected compounds gave either pyrroles or free amine pyrrolines depending on the deprotection conditions. The SES-protected pyrrolines were hydrogenated to yield pyrrolidines with an excellent diastereoselectivity. Free amine pyrrolidines were obtained by HF-mediated deprotection of the SES group.

  4. Stereoselective addition of the titanium enolate of N-acetyl (4S)-isopropyl-1,3-thiazolidine-2-thione to five-membered N-acyl iminium ions.

    PubMed

    Barragán, Efraín; Olivo, Horacio F; Romero-Ortega, Moisés; Sarduy, Seth

    2005-05-13

    [reaction: see text] Addition of the chlorotitanium enolate of N-acetyl 4-isopropyl-1,3-thiazolidine-2-thione to five-membered, N-substituted N-acyl iminium ions furnished the corresponding Mannich-type addition products with good diastereoselectivity and in good yields. The synthetic utility of the addition product 8 was demonstrated in a chemospecific anti-aldol reaction with cinnamaldehyde. By using this strategy, we constructed three contiguous chiral centers with high stereocontrol employing the same chiral auxiliary. X-Ray crystallographic analysis of addition product 2 and aldol product 14 revealed their absolute stereochemistry.

  5. Synthesis of 2-(β-D-glucopyranosylamino)-5-substituted-1,3,4-oxadiazoles for inhibition of glycogen phosphorylase.

    PubMed

    Tóth, Marietta; Szőcs, Béla; Kaszás, Tímea; Docsa, Tibor; Gergely, Pál; Somsák, László

    2013-11-15

    Aromatic aldehyde 4-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)semicarbazones were synthesized by the addition of different hydrazones onto O-peracetylated β-d-glucopyranosyl isocyanate. Oxidative transformations of these precursors gave O-protected 2-(β-d-glucopyranosylamino)-5-substituted-1,3,4-oxadiazoles. Removal of the O-acetyl protecting groups under Zemplén conditions gave test compounds to show low micromolar inhibition against rabbit muscle glycogen phosphorylase b. Best inhibitors of these series were 4-(β-d-glucopyranosyl)semicarbazones of 4-nitrobenzaldehyde (Ki=4.5μM), 2-naphthaldehyde (Ki=5.5μM) and 2-(β-d-glucopyranosylamino)-5-(4-methylphenyl)-1,3,4-oxadiazole (Ki=12μM).

  6. Receptor binding profiles and quantitative structure-affinity relationships of some 5-substituted-N,N-diallyltryptamines.

    PubMed

    Cozzi, Nicholas V; Daley, Paul F

    2016-02-01

    N,N-Diallyltryptamine (DALT) and 5-methoxy-N,N-diallyltryptamine (5-MeO-DALT) are two tryptamines synthesized and tested by Alexander Shulgin. In self-experiments, 5-MeO-DALT was reported to be psychoactive in the 12-20mg range, while the unsubstituted compound DALT had few discernible effects in the 42-80 mg range. Recently, 5-MeO-DALT has been used in nonmedical settings for its psychoactive effects, but these effects have been poorly characterized and little is known of its pharmacological properties. We extended the work of Shulgin by synthesizing additional 5-substituted-DALTs. We then compared them to DALT and 5-MeO-DALT for their binding affinities at 45 cloned receptors and transporter proteins. Based on in vitro binding affinity, we identified 27 potential receptor targets for the 5-substituted-DALT compounds. Five of the DALT compounds had affinity in the 10-80 nM range for serotonin 5-HT1A and 5-HT2B receptors, while the affinity of DALT itself at 5-HT1A receptors was slightly lower at 100 nM. Among the 5-HT2 subtypes, the weakest affinity was at 5-HT2A receptors, spanning 250-730 nM. Five of the DALT compounds had affinity in the 50-400 nM range for serotonin 5-HT1D, 5-HT6, and 5-HT7 receptors; again, it was the unsubstituted DALT that had the weakest affinity at all three subtypes. The test drugs had even weaker affinity for 5-HT1B, 5-HT1E, and 5-HT5A subtypes and little or no affinity for the 5-HT3 subtype. These compounds also had generally nanomolar affinities for adrenergic α2A, α2B, and α2C receptors, sigma receptors σ1 and σ2, histamine H1 receptors, and norepinephrine and serotonin uptake transporters. They also bound to other targets in the nanomolar-to-low micromolar range. Based on these binding results, it is likely that multiple serotonin receptors, as well as several nonserotonergic sites are important for the psychoactive effects of DALT drugs. To learn whether any quantitative structure-affinity relationships existed, we evaluated

  7. Design and Synthesis of 5-Substituted Benzo[d][1,3]dioxole Derivatives as Potent Anticonvulsant Agents.

    PubMed

    Dong, Shiyang; Wang, Tiantian; Hu, Chundi; Chen, Xiaodong; Jin, Yi; Wang, Zengtao

    2017-02-01

    A series of 5-substituted benzo[d][1,3]dioxole derivatives was designed, synthesized, and tested for anticonvulsant activity using the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens. Neurotoxicity was determined by rotarod test. In the preliminary screening, six compounds, 3a, 3c, 3d, and 4d-f, showed promising anticonvulsant activities in the MES model, and compounds 4c and 4d exhibited full protection against seizures at doses of 300 mg/kg in the scPTZ model. Among the synthesized compounds, 3c as the most active compound showed high protection against the MES-induced seizures with an ED50 value of 9.8 mg/kg and a TD50 value of 229.4 mg/kg after intraperitoneal injection into mice, thus providing compound 3c with a high protective index (TD50 /ED50 ) of 23.4 comparable to those of reference antiepileptic drugs. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Growth of epitaxial orthorhombic YO{sub 1.5}-substituted HfO{sub 2} thin film

    SciTech Connect

    Shimizu, Takao; Katayama, Kiliha; Kiguchi, Takanori; Akama, Akihiro; Konno, Toyohiko J.; Funakubo, Hiroshi

    2015-07-20

    YO{sub 1.5}-substituted HfO{sub 2} thin films with various substitution amounts were grown on (100) YSZ substrates by the pulsed laser deposition method directly from the vapor phase. The epitaxial growth of film with different YO{sub 1.5} amounts was confirmed by the X-ray diffraction method. Wide-area reciprocal lattice mapping measurements were performed to clarify the crystal symmetry of films. The formed phases changed from low-symmetry monoclinic baddeleyite to high-symmetry tetragonal/cubic fluorite phases through an orthorhombic phase as the YO{sub 1.5} amount increased from 0 to 0.15. The additional annular bright-field scanning transmission electron microscopy indicates that the orthorhombic phase has polar structure. This means that the direct growth by vapor is of polar orthorhombic HfO{sub 2}-based film. Moreover, high-temperature X-ray diffraction measurements showed that the film with a YO{sub 1.5} amount of 0.07 with orthorhombic structure at room temperature only exhibited a structural phase transition to tetragonal phase above 450 °C. This temperature is much higher than the reported maximum temperature of 200 °C to obtain ferroelectricity as well as the expected temperature for real device application. The growth of epitaxial orthorhombic HfO{sub 2}-based film helps clarify the nature of ferroelectricity in HfO{sub 2}-based films (186 words/200 words)

  9. Synthesis of 2-phenyl-4,5-substituted oxazoles by copper-catalyzed intramolecular cyclization of functionalized enamides.

    PubMed

    Vijay Kumar, S; Saraiah, B; Misra, N C; Ila, H

    2012-12-07

    An efficient two-step synthesis of 2-phenyl-4,5-substituted oxazoles involving intramolecular copper-catalyzed cyclization of highly functionalized novel β-(methylthio)enamides as the key step has been reported. These enamides are obtained by nucleophilic ring-opening of newly synthesized 4-[(methylthio)hetero(aryl)methylene]-2-phenyl-5-oxazolone precursors by alkoxides, amines, amino acid esters and aryl/alkyl Grignard reagents, thus leading to the introduction of an ester, N-substituted carboxamide or acyl functionalities at 4-position of the product oxazoles. Synthesis of two naturally occurring 2,5-diaryloxazoles, i.e., texamine and uguenenazole, via two-step hydrolysis-decarboxylation of the corresponding 2,5-diaryloxazole-4-carboxylates has also been described. Similarly, three of the serine-derived oxazole-4-carboxamides were elaborated to novel trisubstituted 4,2'-bisoxazoles through DAST/DBU-mediated cyclodehydration-dehydrohalogenation sequence. The present protocol is complementary and an improvement to our previously reported silver carbonate-induced cyclization of β-bis(methylthio)enamides to 2-phenyl-5-(methylthio)-4-substituted oxazoles.

  10. Synthesis of 5-substituted 1H-tetrazoles by the copper-catalyzed [3+2] cycloaddition of nitriles and trimethylsilyl azide.

    PubMed

    Jin, Tienan; Kitahara, Fukuzou; Kamijo, Shin; Yamamoto, Yoshinori

    2008-09-01

    The copper-catalyzed [3+2] cycloaddition between various nitriles and trimethylsilyl azide in DMF/MeOH produced the corresponding 5-substituted 1H-tetrazoles in good to high yields. It was proposed that the reaction proceeds through the formation in situ of a copper azide species and subsequent [3+2] cycloaddition with the nitriles. Furthermore, we found that a copper and triethylamine combined catalyst also promoted the cycloaddition of nitriles and trimethylsilyl azide to afford the 5-substituted 1H-tetrazoles at relatively low reaction temperatures. The copper azide species would be formed by reaction of the copper catalyst with Et(3)NHN(3) generated in situ.

  11. Multicomponent, one-pot sequential synthesis of 1,3,5- and 1,3,5,5-substituted barbiturates.

    PubMed

    Volonterio, Alessandro; Zanda, Matteo

    2008-10-03

    Carbodiimides and malonic acid monoethylesters readily react to afford N-acylurea derivatives that could be cyclized in situ by addition of a suitable base. This process represents a general and straightforward one-pot sequential synthesis of 1,3,5-trisubstituted barbiturates in very mild conditions (organic solvent/2 N NaOH aqueous solution, 20 degrees C). Performing the reaction in the presence of an electrophile resulted in the formation of fully substituted (namely, 1,3,5,5-tetrasubstituted) barbiturates through a three-component one-pot sequential process. The latter, however, occurred only with highly reactive electrophiles, such as benzyl and, in some instances, allyl halides. In order to expand the scope of the process, we sought to develop a general method for the C-alkylation of 1,3,5-trisubstituted barbiturates. We found that C-alkylation occurred upon treatment of 1,3,5-trisubstituted barbiturates with an alkyl halide in CH3CN at 120 degrees C in the presence of anhydrous K2CO3 affording the target 1,3,5,5-tetrasubstituted barbiturates in good yields. The multicomponent process was accomplished by combining the three steps in a one-pot sequential fashion, i.e., the condensation of carbodiimides with malonic acid monoethylesters, the cyclization of the resulting N-acylureas, and the C-alkylation of the resulting 1,3,5-substituted barbiturates. A detailed study of the influence of the structure of the reactants on the reaction outcome and mechanism is presented. By selective N'-deprotection of 1,3,5,5-tetrasubstituted barbiturates, the corresponding 1,5,5-trisubstituted barbiturates were also prepared.

  12. Design and synthesis of 5-(substituted benzylidene)thiazolidine-2,4-dione derivatives as novel tyrosinase inhibitors.

    PubMed

    Ha, Young Mi; Park, Yun Jung; Kim, Jin-Ah; Park, Daeui; Park, Ji Young; Lee, Hye Jin; Lee, Ji Yeon; Moon, Hyung Ryong; Chung, Hae Young

    2012-03-01

    In continuing our search for novel tyrosinase inhibitors, a series of 5-(substituted benzylidene)thiazolidine-2,4-diones were rationally designed and synthesized, and their inhibitory effects on mushroom tyrosinase activity were evaluated. Twelve target compounds 2a-2l were designed and synthesized based on the structural characteristics of N-phenylthiourea, a tyrosinase inhibitor, and tyrosine and L-DOPA, the natural substrates of tyrosinase. Among them, (Z)-5-(4-hydroxybenzylidene)thiazolidine-2,4-dione (2a) and (Z)-5-(3-hydroxy-4-methoxybenzylidene)thiazolidine-2,4-dione (2f) exhibited much higher tyrosinase inhibitory activities, with IC(50) values of 13.36 and 9.87 μM, respectively, than kojic acid (IC(50) = 24.72 μM). Kinetic analysis of tyrosinase inhibition revealed that 2a and 2f are competitive inhibitors of mushroom tyrosinase. In addition, through prediction of the potato catechol oxidase tertiary structure and simulation of docking with compounds 2a and 2f using DOCK6, we found that these inhibitors likely bind to the active site of the enzyme. Docking simulation results suggested that 2a and 2f have high binding affinities with potato catechol oxidase. In addition, compounds 2a and 2f effectively inhibited tyrosinase activity and reduced melanin levels in B16 cells treated with α-melanocyte-stimulating hormone (α-MSH). These data strongly suggest that compounds 2a and 2f suppress the production of melanin via the inhibition of tyrosinase activity.

  13. A density functional theory study on the kinetics and thermodynamics of N-glycosidic bond cleavage in 5-substituted 2'-deoxycytidines.

    PubMed

    Williams, Renee T; Wang, Yinsheng

    2012-08-14

    B3LYP/6-311+G(2d,p)//B3LYP/6-31+G(d) density functional theory calculations were employed to explore the kinetics and thermodynamics of gas-phase N-glycosidic bond cleavage induced by nucleophilic attack of C1' with a hydroxide ion in 5-substituted 2'-deoxycytidines. The results showed that, among the 5-substituted 2'-deoxycytidine derivatives examined [XdC, where X = H (dC), CH(3) (medC), CH(2)OH (hmdC), CHO (fmdC), COOH (cadC), F (FdC), or Br (BrdC)], fmdC and cadC exhibited the lowest energy barrier and largest exothermicity for N-glycosidic bond cleavage. These results paralleled previously reported nucleobase excision activities of human thymine DNA glycosylase (hTDG) toward duplex DNA substrates harboring a thymine and 5-substituted cytosine derivatives when paired with a guanine. Our study suggests that the inherent chemistry associated with the nucleophilic cleavage of N-glycosidic bond constitutes a major factor contributing to the selectivity of hTDG toward 5-substituted dC derivatives. These findings provided novel insights into the role of TDG in active cytosine demethylation.

  14. Scaffold oriented synthesis. Part 4: design, synthesis and biological evaluation of novel 5-substituted indazoles as potent and selective kinase inhibitors employing heterocycle forming and multicomponent reactions.

    PubMed

    Akritopoulou-Zanze, Irini; Wakefield, Brian D; Gasiecki, Alan; Kalvin, Douglas; Johnson, Eric F; Kovar, Peter; Djuric, Stevan W

    2011-03-01

    We report the synthesis and biological evaluation of 5-substituted indazoles as kinase inhibitors. The compounds were synthesized in a parallel synthesis fashion from readily available starting materials employing heterocycle forming and multicomponent reactions and were evaluated against a panel of kinase assays. Potent inhibitors were identified for Gsk3β, Rock2, and Egfr.

  15. Theoretical studies of the structure, stability, and detonation properties of vicinal-tetrazine 1,3-dioxide annulated with a five-membered heterocycle. 1. Annulation with a triazole ring.

    PubMed

    Wang, Tianyi; Zheng, Chunmei; Liu, Yan; Gong, Xuedong; Xia, Mingzhu

    2015-08-01

    1,2,3,4-Tetrazine (vicinal-tetrazine) high-energy-density compounds (HEDCs) are receiving increasing attention due to their promise as explosives. We have performed a series of studies of vicinal-tetrazine 1,3-dioxides annulated with a range of five-membered heterocycles, considering their potential as high-energy, low-sensitivity explosives. In the present work, twelve 1,2,3-triazol-1,2,3,4-tetrazine 1,3-dioxides (TTDOs; T1-T12) were studied theoretically. Their geometric structures in the gas phase were studied at the B3LYP/6-311++G(d,p) level of density functional theory (DFT). Their gas-phase enthalpies of formation were calculated by the homodesmotic reaction method. Their enthalpies of sublimation and solid-phase enthalpies of formation were also predicted. Their detonation properties were estimated with the Kamlet-Jacobs equations, based on their predicted densities and enthalpies of formation in the solid state. Their bond dissociation activation energies (BDAEs) and the available free space in the lattice of each compound were calculated to evaluate their stabilities. T2, T5, and T11 were found to have higher energies than RDX and acceptable stabilities, and are therefore considered to be the three most promising TTDOs for use as high-energy, low-sensitivity explosives. We believe that further studies, both experimental and theoretical, of these three targets would be worthwhile.

  16. Theoretical studies of the structure, stability, and detonation properties of vicinal-tetrazine 1,3-dioxide annulated with a five-membered heterocycle. 2. Annulation with a pyrazole ring.

    PubMed

    Wang, Tianyi; Zheng, Chunmei; Gong, Xuedong; Xia, Mingzhu

    2015-10-01

    1,2,3,4-Tetrazine (vicinal-tetrazine) high-energy-density compounds (HEDCs) are receiving increasing attention due to their promise as explosives. We have performed a series of studies of vicinal-tetrazine 1,3-dioxides annulated with a range of five-membered heterocycles, considering their potential as high-energy, low-sensitivity explosives. In the present work, 12 pyrazolo-1,2,3,4-tetrazine 1,3-dioxides (pyrazolo-TDOs), P1-P12, were studied theoretically. Their geometrical structures in the gas phase were studied at the B3LYP/6-311++G(d,p) level of density functional theory (DFT). Their gas-phase enthalpies of formation were calculated by the homodesmotic reaction method. Their enthalpies of sublimation and solid phase enthalpies of formation were also predicted. Their detonation properties were estimated with the Kamlet-Jacobs equations, based on their predicted densities and enthalpies of formation in the solid state. Their bond dissociation activation energies (BDAEs) and the available free space in the lattice of each compound were calculated to evaluate their stabilities. P1, P4, and P11 were found to achieve the energy level of RDX and have acceptable stabilities, and are therefore considered to be the three most promising pyrazolo-TDOs for use as high-energy, low-sensitivity explosives. We believe that further studies, both experimental and theoretical, of these three targets would be worthwhile.

  17. Scaffold oriented synthesis. Part 3: design, synthesis and biological evaluation of novel 5-substituted indazoles as potent and selective kinase inhibitors employing [2+3] cycloadditions.

    PubMed

    Akritopoulou-Zanze, Irini; Wakefield, Brian D; Gasiecki, Alan; Kalvin, Douglas; Johnson, Eric F; Kovar, Peter; Djuric, Stevan W

    2011-03-01

    We report the synthesis and biological evaluation of 5-substituted indazoles and amino indazoles as kinase inhibitors. The compounds were synthesized in a parallel synthesis fashion from readily available starting materials employing [2+3] cycloaddition reactions and were evaluated against a panel of kinase assays. Potent inhibitors were identified for numerous kinases such as Rock2, Gsk3β, Aurora2 and Jak2.

  18. Eco-friendly synthesis and antimicrobial activities of some 1-phenyl-3(5-bromothiophen-2-yl)-5-(substituted phenyl)-2-pyrazolines.

    PubMed

    Sasikala, Ramalingam; Thirumurthy, Kannan; Mayavel, Perumal; Thirunarayanan, Ganesamoorthy

    2012-06-11

    Green catalyst fly ash: H2SO4 was prepared by mixing fly ash and sulphuric acid. Microwave irradiations are applied for solid phase cyclization of 5-bromo-2-thienyl chalcones and phenyl hydrazine hydrate in the presence of fly ash: H2SO4 yields, 1-phenyl-3(5-bromothiophen-2-yl)-5-(substituted phenyl)-2-pyrazolines. These pyrazolines were characterized by their physical constants and spectral data. The antimicrobial activities of all synthesized pyrazolines have been studied. Scanning electron microscopy (SEM) analysis shows the morphology changes between fly ash and the catalyst fly ash: H2SO4. The SEM photographs with the scale of 1 and 50 μm show the fly-ash particle is corroded by H2SO4 (indicated by arrow mark), and this may be due to dissolution of fly ash by H2SO4. The yields of 1-phenyl-3(5-bromothiophen-2-yl)-5-(substituted phenyl)-2-pyrazolines is more than 75% using this catalyst under microwave heating. All pyrazolines showed moderate activities against antimicrobial strains. We have developed an efficient catalytic method for synthesis of 1-phenyl-3(5-bromothiophen-2-yl)-5-(substituted phenyl)-2-pyrazolines by solid phase cyclization using a solvent-free environmentally greener catalyst fly ash: H2SO4 under microwave irradiation between aryl chalcones and hydrazine hydrate. This reaction protocol offers a simple, economical, environment friendly, non-hazardous, easier work-up procedure, and good yields. All synthesized pyrazoline derivatives showed moderate antimicrobial activities against bacterial and fungal strains.

  19. Stereochemistry of N-Benzoyl-5-substituted-1-benzazepines Revisited: Synthesis of the Conformationally Biased Derivatives and Revision of the Reported Structure.

    PubMed

    Tabata, Hidetsugu; Yoneda, Tetsuya; Tasaka, Tomohiko; Ito, Shigekazu; Oshitari, Tetsuta; Takahashi, Hideyo; Natsugari, Hideaki

    2016-04-15

    The syn (aR*,5R*) and anti (aS*,5R*) diastereomers of N-benzoyl-C5-substituted-1-benzazepines originating in the chiralities at C5 and the Ar-N(C═O) axis were first stereoselectively synthesized by biasing the conformation with a substituent at C6 and C9, respectively. Detailed examination of the stereochemistry (i.e., conformation and configuration) of these N-benzoyl-1-benzazepines by X-ray crystallographic analysis, VT NMR, and DFT calculations revealed new physicochemical aspects of these heterocycles including revision of the stereochemistry previously reported.

  20. Ferric Hydrogensulfate [Fe(HSO4)3] As a Reusable Heterogeneous Catalyst for the Synthesis of 5-Substituted-1H-Tetrazoles and Amides

    PubMed Central

    Eshghi, Hossein; Seyedi, Seyed Mohammad; Zarei, Elaheh Rahimi

    2011-01-01

    Ferric hydrogensulfate catalyzed the synthesis of 5-substituted 1H-tetrazoles via [2 + 3] cycloaddition of nitriles and sodium azide. This method has the advantages of high yields, simple methodology, and easy workup. The catalyst can be recovered by simple filtration and reused delivering good yields. Also, ferric hydrogensulfate catalyzed the hydrolysis of nitriles to primary amides under aqueous conditions. Various aliphatic and aromatic nitriles converted to the corresponding amides in good yields without any contamination with carboxylic acids. PMID:24052817

  1. A novel ring oxidation of 4- or 5-substituted 2H-oxazole to corresponding 2-oxazolone catalyzed by cytosolic aldehyde oxidase.

    PubMed

    Arora, Vinod K; Philip, Thomas; Huang, Stella; Shu, Yue-Zhong

    2012-09-01

    The ring oxidation of 2H-oxazole, or C2-unsubstituted oxazole, to 2-oxazolone, a cyclic carbamate, was observed on various 4- or 5-substituted oxazoles. Using 5-(3-bromophenyl)oxazole as a model compound, its 2-oxazolone metabolite M1 was fully characterized by liquid chromatography/tandem mass spectrometry and nuclear magnetic resonance. The reaction mainly occurred in the liver cytosolic fraction without the requirement of cytochrome P450 enzymes and cofactor NADPH. Investigations into the mechanism of formation of 2-oxazolone using various chemical inhibitors indicated that the reaction was primarily catalyzed by aldehyde oxidase and not by xanthine oxidase. In addition, cytosol incubation of 5-(3-bromophenyl)oxazole in the medium containing H₂¹⁸O led to the ¹⁸O incorporation into M1, substantiating the reaction mechanism of a typical molybdenum hydroxylase. The rank order of liver cytosols for the 2-oxazolone formation was mouse > monkey ≫ rat and human liver cytosol, whereas M1 was not formed in dog liver cytosol. Because the reaction was observed with a number of 4- or 5-substituted 2H-oxazoles in mouse liver cytosols, 2H-oxazoles represent a new substrate chemotype for ring oxidation catalyzed by aldehyde oxidase.

  2. Synthesis and antibacterial activity of pyridinium-tailored 2,5-substituted-1,3,4-oxadiazole thioether/sulfoxide/sulfone derivatives.

    PubMed

    Wang, Pei-Yi; Zhou, Lei; Zhou, Jian; Wu, Zhi-Bing; Xue, Wei; Song, Bao-An; Yang, Song

    2016-02-15

    By introducing the pyridinium group into 2,5-substituted-1,3,4-oxadiazole, a series of pyridinium-tailored 2,5-substituted-1,3,4-oxadiazole thioether/sulfoxide/sulfone derivatives were obtained, and their antibacterial activities were evaluated via turbidimeter test in vitro. The bioassays reveal that most of the target compounds exhibit better inhibition activities against pathogen Xanthomonas oryzae pv. oryzae, Ralstonia solanacearum, and Xanthomonas axonopodis pv. citri than positive controls bismerthiazol (CK1) or thiodiazole copper (CK2). Among them, I-8, I-10, I-12, II-10, II-12, III-10, and III-12 exert excellent inhibition activities against the three pathogenic bacteria with the half-maximal effective concentration (EC50) values ranging from 0.54 to 12.14 μg/mL. Our results demonstrate that pyridinium-tailored 1,3,4-oxadiazole thioether/sulfoxide/sulfone derivatives can serve as potential alternative bactericides for the management of plant bacterial diseases.

  3. Arylsulfanyl groups - Suitable side chains for 5-substituted 1,10-phenanthroline and nickel complexes as G4 ligands and telomerase inhibitors.

    PubMed

    Liu, Wanbo; Wang, Siwen; Dotsenko, Irina A; Samoshin, Vyacheslav V; Xue, Liang

    2017-08-01

    Guanine-rich DNA sequences can undergo self-assembly into unique G-quadruplex structures that interfere with the binding of proteins to the same DNA region. The formation of DNA G-quadruplexes requires monovalent cations (Na(+) and K(+)) or small molecules known as G-quadruplex (G4) ligands. Phenanthroline is a type of G4 ligand scaffold known for its coordination with metal ions to form complexes with a large aromatic surface area, which aptly stack with G-quartets. In this report, we have investigated the side chain effect on G-quadruplex recognition by evaluating a series of 5-substituted phenanthroline-based metal complexes (Phen-Ni) binding to telomeric G-quadruplex DNA. Results from biophysical methods including fluorescence and circular dichroism (CD) thermal denaturation, CD titration, and the fluorescent intercalator displacement (FID) assay suggest that several Phen-Ni complexes bind to G-quadruplex DNA with submicromolar (G4)DC50 values. Arylsulfanyl groups at the 5 position of 1,10-phenanthroline are the best side chains regarding binding affinity and selectivity towards G-quadruplex DNA. Most of the G-quadruplex binding Phen-Ni complexes can inhibit telomerase activity in vitro as indicated by the telomeric repeat amplification protocol (TRAP) assay and such inhibition is clearly concentration dependent. Our results here provide a guidance of utilizing 5-substituted phenanthroline derivatives as a viable and facile approach to design novel G4 ligands. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. A vibrational circular dichroism approach to the determination of the absolute configurations of flavorous 5-substituted-2(5H)-furanones.

    PubMed

    Nakahashi, Atsufumi; Yaguchi, Yoshihiro; Miura, Nobuaki; Emura, Makoto; Monde, Kenji

    2011-04-25

    Sotolon (1) and maple furanone (2) are naturally occurring chiral furanones. These 5-substituted-2(5H)-furanones are industrially significant aroma compounds due to their characteristic organoleptic properties and extraordinarily low odor thresholds. Each enantiomer of 1 and 2 was successfully obtained by preparative enantioselective supercritical fluid chromatography. The absolute configuration of 1 was confirmed as (R)-(-)-1 and (S)-(+)-1 by adopting the vibrational circular dichroism (VCD) approach. The absolute configuration of 2, which has remained ambiguous since its discovery in 1957, was determined as (R)-(+)-2 and (S)-(-)-2 for the first time by the VCD technique. Surprisingly, the signs of the optical rotation of 2 are opposite of those of 1 regardless of their identical absolute configurations. This observation emphasizes the risk in absolute configurational assignments based on comparison of optical rotation signs of similar structures. Odor evaluation of the enantiomers of 2 revealed different odor intensities.

  5. Synthesis of ω-Oxo Amino Acids and trans-5-Substituted Proline Derivatives Using Cross-Metathesis of Unsaturated Amino Acids.

    PubMed

    Salih, Nabaz; Adams, Harry; Jackson, Richard F W

    2016-09-16

    A range of 7-oxo, 8-oxo, and 9-oxo amino acids, analogues of 8-oxo-2-aminodecanoic acid, one of the key components of the cyclic tetrapeptide apicidin, have been prepared by a three-step process involving copper-catalyzed allylation of serine-, aspartic acid-, and glutamic acid-derived organozinc reagents, followed by cross-metathesis of the resulting terminal alkenes with unsaturated ketones and hydrogenation. The intermediate 7-oxo-5-enones underwent a highly diastereoselective (dr ≥96:4) acid-catalyzed aza-Michael reaction to give trans-2,5-disubstituted pyrrolidines, 5-substituted proline derivatives. The aza-Michael reaction was first observed when the starting enones were allowed to stand in solution in deuterochloroform but can be efficiently promoted by catalytic amounts of dry HCl.

  6. Incorporation of 5-substituted pyrimidine nucleoside analogues into DNA of a thymidylate synthetase-deficient murine FM3A carcinoma cell line.

    PubMed

    Balzarini, J; De Clercq, E; Ayusawa, D; Seno, T

    1985-01-01

    Various 5-substituted 2'-deoxyuridine (dUrd), 2'-deoxycytidine (dCyd), 1-beta-D-arabinofuranosyluracil (araU) and 1-beta-D-arabinofuranosylcytosine (araC) analogues have been investigated for their stimulatory effect on the growth of a thymidylate (dTMP) synthetase-deficient murine mammary carcinoma cell line (FM3A/TS-) that is auxotrophic for thymidine (dThd). Such stimulatory effect may be considered as indicative for the incorporation of the nucleoside analogue into host cell DNA. Based on this premise, several dUrd analogues were found to be incorporated into FM3A/TS- cell DNA (in decreasing order of incorporation): 5-bromo-dUrd greater than 5-chloro-dUrd greater than 5-(3-hydroxy-1-propynyl)-dUrd greater greater than 5-(1-pentynyl)-dUrd approximately 5-(1-propynyl)-dUrd approximately 5-iodo-dUrd greater than 5-(5-carboxy-1-hexenyl)-dUrd greater than 5-(3,3-dimethyl-1-butynyl)-dUrd greater than 5-ethyl-dUrd greater than 5-(5-chloro-1-pentynyl)-dUrd greater than 5-ethynyl-dUrd approximately 5 vinyl-dUrd greater than 5-phenylethynyl-dUrd greater than 5-(5-cyano-1-pentenyl)-dUrd greater than 5-(1-propenyl)-dUrd greater than 5-(1-hexynyl)-dUrd greater than 5-(5-hexyn-1-enyl)-dUrd. Among the 5-substituted dCyd analogues, 5-methyl-dCyd, 5-chloro-dCyd, 5-bromo-dCyd and 5-iodo-dCyd were also found to stimulate cell growth, and are therefore assumed to be incorporated into FM3A/TS- cell DNA. Since the stimulatory effects of these compounds on FM3A/TS- cell proliferation were suppressed in the presence of a Cyd deaminase inhibitor (tetrahydrouridine) or dCMP deaminase inhibitor (2'-deoxytetrahydrouridine), it is surmised that the dCyd analogues are first deaminated to the corresponding dUrd analogues before they are incorporated into DNA. None of the 5-substituted araU or araC analogues tested were able to sustain the growth of FM3A/TS- cells. It is postulated, therefore, that these araU or araC analogues are not incorporated to any appreciable extent into the DNA of FM3

  7. Synthesis and antimicrobial evaluation of L-phenylalanine-derived C5-substituted rhodanine and chalcone derivatives containing thiobarbituric acid or 2-thioxo-4-thiazolidinone.

    PubMed

    Jin, Xin; Zheng, Chang-Ji; Song, Ming-Xia; Wu, Yan; Sun, Liang-Peng; Li, Yin-Jing; Yu, Li-Jun; Piao, Hu-Ri

    2012-10-01

    Four novel series of compounds, including the l-phenylalanine-derived C5-substituted rhodanine (6a-q, 7a-j) and chalcone derivatives containing thiobarbituric acid or 2-thioxo-4-thiazolidinone (9a-e, 11a-e) have been designed, synthesized, characterized, and evaluated for their antibacterial activity. Some of these compounds showed significant antibacterial activity against Gram-positive bacterias, especially against the strains of multidrug-resistant clinical isolates, among which compounds 6c-e, 6g, 6i, 6j and 6q exhibiting high levels of antimicrobial activity against Staphylococcus aureus RN4220 with minimum inhibitory concentration (MIC) values of 2 μg/mL. Compound 6q showed the most potent activity of all of the compounds against all of the test multidrug-resistant clinical isolates tested. Unfortunately, however, none of the compounds were active against Gram-negative bacteria at 64 μg/mL. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  8. CNS depressant and anticonvulsant activities of some novel 3-[5-substituted 1,3,4-thiadiazole-2-yl]-2-styryl quinazoline-4(3H)-ones.

    PubMed

    Jatav, Varsha; Mishra, Pradeep; Kashaw, Sushil; Stables, J P

    2008-09-01

    A series of new 3-[5-substituted phenyl-1,3,4-thiadiazole-2-yl]-2-styryl quinazoline-4(3H)-ones were synthesized and evaluated for anticonvulsant, sedative-hypnotic and CNS depression activities. After i.p. injection to mice or rat at doses of 30, 100, and 300 mg/kg body weight 2-styryl quinazolin-4(3H)-ones derivatives were examined in the maximal electroshock (MES) induced seizures and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. Rotorod method was employed to determine the neurotoxicity. Out of 18 compounds only 4a, 4e and 4p showed anticonvulsant activity in one or more test models. All except 4l and 4q exhibited significant sedative-hypnotic activity via actophotometer screen. Forced swim pool method to determine CNS depressant activity resulted in some potent compounds. It can be concluded that synthesized compounds exhibited better sedative-hypnotic and CNS depressant activities than anticonvulsant activity.

  9. Synthesis and CNS depressant activity of some novel 3-[5-substituted 1,3,4-thiadiazole-2-yl]-2-styryl quinazoline-4(3H)-ones.

    PubMed

    Jatav, Varsha; Mishra, Pradeep; Kashaw, Sushil; Stables, J P

    2008-01-01

    A series of novel 3-[5-substituted phenyl-1,3,4-thiadiazole-2-yl]-2-styryl quinazoline-4(3H)-ones were synthesized and evaluated for anticonvulsant, sedative-hypnotic and CNS depressant activities. After i.p. injection to mice at doses of 30, 100, and 300mg/kg body weight 2-styrylquinazolin-4(3H)-one derivatives were examined in the maximal electroshock induced seizures (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. The neurotoxicity was assessed using the rotorod method. Out of eighteen compounds only 4a, 4d, 4e, 4j and 4k showed anticonvulsant activity in one or more test models. All except 4e and 4f exhibited significant sedative-hypnotic activity via actophotometer screen. CNS depressant activity screened with the help of the forced swim pool method resulted into some potent compounds. From the experimental observation it can be concluded that synthesized compounds exhibited relatively better sedative-hypnotic and CNS depressant activities.

  10. Design, synthesis and biological evaluation of 5-hydroxy, 5-substituted-pyrimidine-2,4,6-triones as potent inhibitors of gelatinases MMP-2 and MMP-9.

    PubMed

    Nicolotti, Orazio; Catto, Marco; Giangreco, Ilenia; Barletta, Maria; Leonetti, Francesco; Stefanachi, Angela; Pisani, Leonardo; Cellamare, Saverio; Tortorella, Paolo; Loiodice, Fulvio; Carotti, Angelo

    2012-12-01

    Matrix metalloproteinases (MMPs) are attractive biological targets that play a key role in many physiopathological processes such as degradation of extracellular matrix proteins, release and cleavage of cell-surface receptors, tumour progression, homeostatic regulation and innate immunity. A series of 5-hydroxy, 5-substituted pyrimidine-2,4,6-triones were rationally designed, prepared and tested as inhibitors of gelatinases MMP-2 and MMP-9 and collagenase MMP-8. On one side, the presence of the 5-hydroxyl group, that represents an typical feature of this class of compounds, ensured an attractive pharmacokinetic profile while on the other suitably substituted biaryl molecular fragments, attached to position 5 through a ketomethylene linker, guaranteed favourable interaction in the deep region of the S(1)' enzymatic subsite. This rational design led to the discovery of highly potent MMP inhibitors. In particular, biphenyl derivatives bearing at the para position COCH(3) and OCF(3) substituents permitted to inhibit gelatinases MMP-2 and MMP-9, with IC(50) values as low as 30 nM and 21 nM, respectively, whereas the introduction at the same position of the bulkier SO(2)CH(3) group afforded a potent collagenase MMP-8 inhibitor with an IC(50) value equal to 66 nM. Molecular docking simulations allowed us to elucidate key interactions driving the binding of the top active compounds towards their preferred MMP target.

  11. Design, synthesis, and antibacterial activity against rice bacterial leaf blight and leaf streak of 2,5-substituted-1,3,4-oxadiazole/thiadiazole sulfone derivative.

    PubMed

    Li, Pei; Shi, Li; Yang, Xia; Yang, Lei; Chen, Xue-Wen; Wu, Fang; Shi, Qing-Cai; Xu, Wei-Ming; He, Ming; Hu, De-Yu; Song, Bao-An

    2014-04-01

    A series of 2,5-substituted-1,3,4-oxadiazole/thiadiazole sulfone derivatives were synthesized and evaluated for their antibacterial activities against rice bacterial leaf blight and leaf streak caused by Xanthomonas oryzae pv. oryzae and Xanthomonas oryzae pv. oryzicolaby via the turbidimeter test in vitro. Antibacterial bioassay results indicated that most compounds demonstrated good inhibitory effect antibacterial bioactivities against rice bacterial leaf blight and leaf streak. Among the title compounds, compound 6c demonstrated the best inhibitory effect against rice bacterial leaf blight and leaf streak with half-maximal effective concentration (EC50) values of 1.07 and 7.14 μg/mL, respectively, which were even better than those of commercial agents such as Bismerthiazol and Thiediazole Copper. In vivo antibacterial activities tests at greenhouse conditions demonstrated that the controlling effect of compounds 6c (43.5%) and 6g (42.4%) against rice bacterial leaf blight were better than those of Bismerthiazol (25.5%) and Thiediazole Copper (37.5%).

  12. Antibacterial activities against rice bacterial leaf blight and tomato bacterial wilt of 2-mercapto-5-substituted-1,3,4-oxadiazole/thiadiazole derivatives.

    PubMed

    Li, Pei; Shi, Li; Gao, Man-Ni; Yang, Xia; Xue, Wei; Jin, Lin-Hong; Hu, De-Yu; Song, Bao-An

    2015-02-01

    In this study, a series of 2-mercapto-5-substituted-1,3,4-oxadiazole/thiadiazole derivatives were synthesized and evaluated for their antibacterial activities against rice bacterial leaf blight and tomato bacterial wilt caused by Xanthomonas oryzae pv. oryzae (Xoo) and Ralstonia solanacearum (R. solanacearum) via the turbidimeter test in vitro. Antibacterial bioassays indicated that most compounds demonstrated appreciable antibacterial bioactivities against Xoo and R. solanacearum. Among the title compounds, compound 4i demonstrated the best inhibitory effect against Xoo and R. solanacearum with half-maximal effective concentration (EC50) values of 14.69 and 15.14μg/mL, respectively, which were even better than those of commercial agents Bismerthiazol and Thiodiazole Copper. In vivo antibacterial activities tests under greenhouse conditions revealed that the control efficiency of compound 4i against rice bacterial leaf blight and tobacco bacterial wilt were better than those of Bismerthiazol and Thiodiazole Copper. Meanwhile, field trials also indicated that compound 4i demonstrated appreciable control efficiency against rice bacterial leaf blight and tomato bacterial wilt.

  13. Discovery of 5-substituted tetrahydronaphthalen-2yl-methyl with N-phenyl-N-(piperidin-4-yl)propionamide derivatives as potent opioid receptor ligands.

    PubMed

    Deekonda, Srinivas; Wugalter, Lauren; Kulkarni, Vinod; Rankin, David; Largent-Milnes, Tally M; Davis, Peg; Bassirirad, Neemah M; Lai, Josephine; Vanderah, Todd W; Porreca, Frank; Hruby, Victor J

    2015-09-15

    A new series of novel opioid ligands have been designed and synthesized based on the 4-anilidopiperidine scaffold containing a 5-substituted tetrahydronaphthalen-2yl)methyl group with different N-phenyl-N-(piperidin-4-yl)propionamide derivatives to study the biological effects of these substituents on μ and δ opioid receptor interactions. Recently our group reported novel 4-anilidopiperidine analogues, in which several aromatic ring-contained amino acids were conjugated with N-phenyl-N-(piperidin-4-yl)propionamide and examined their biological activities at the μ and δ opioid receptors. In continuation of our efforts in these novel 4-anilidopiperidine analogues, we took a peptidomimetic approach in the present design, in which we substituted aromatic amino acids with tetrahydronaphthalen-2yl methyl moiety with amino, amide and hydroxyl substitutions at the 5th position. In in vitro assays these ligands, showed very good binding affinity and highly selective toward the μ opioid receptor. Among these, the lead ligand 20 showed excellent binding affinity (2 nM) and 5000 fold selectivity toward the μ opioid receptor, as well as functional selectivity in GPI assays (55.20 ± 4.30 nM) and weak or no agonist activities in MVD assays. Based on the in vitro bioassay results the lead compound 20 was chosen for in vivo assessment for efficacy in naïve rats after intrathecal administration. Compound 20 was not significantly effective in alleviating acute pain. This discrepancy between high in vitro binding affinity, moderate in vitro activity, and low in vivo activity may reflect differences in pharmacodynamics (i.e., engaging signaling pathways) or pharmacokinetics (i.e., metabolic stability). In sum, our data suggest that further optimization of this compound 20 is required to enhance in vivo activity.

  14. Pronounced in vitro and in vivo antiretroviral activity of 5-substituted 2,4-diamino-6-[2-(phosphonomethoxy)ethoxy] pyrimidines.

    PubMed

    Balzarini, Jan; Schols, Dominique; Van Laethem, Kristel; De Clercq, Erik; Hocková, Dana; Masojidkova, Milina; Holý, Antonin

    2007-01-01

    To discover new potent and selective anti-human immunodeficiency virus (HIV) acyclic nucleoside phosphonate (ANP) drugs with in vivo antiretroviral activity. New acyclic pyrimidine nucleoside phosphonate derivatives that mimic the structure of the anti-HIV purine nucleoside phosphonates 9-(2-phosphonylmethoxyethyl)adenine (PMEA, adefovir) and (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA, tenofovir) were designed by linking the acyclic side chain of the ANPs through an ether bond to the C-6 position instead of the N-1 position of the pyrimidine ring. The compounds were evaluated against HIV and Moloney murine sarcoma virus (MSV) in cell culture, including a broad variety of HIV-1 clade clinical isolates and relevant mutant (drug-resistant) HIV-1 isolates. Their antiviral activities were correlated and investigated in an in vivo model consisting of MSV-infected newborn mice. MSV-induced tumour formation and associated death were recorded in drug-treated animals. Several 5-substituted 6-[2-(phosphonomethoxy)ethoxy]-2,4-diaminopyrimidine (PMEO-DAPy) analogues were found to inhibit a broad variety of HIV-1 clinical isolates. They showed a more favourable cross-resistance profile to mutant virus isolates than adefovir and tenofovir. There was a close correlation between inhibition of MSV in C3H/3T3 cells and inhibition of HIV-1 in CEM cells. The PMEO-DAPy derivatives potently inhibited MSV-induced tumour cell formation in newborn mice. The 5-methyl analogue PMEO-5-Me-DAPy proved markedly more inhibitory to MSV-induced tumour cell formation and associated animal death than its unsubstituted parent PMEO-DAPy derivative. When compared with adefovir, PMEO-5-Me-DAPy was less toxic and more antivirally active in MSV-infected mice. PMEO-5-Me-DAPy deserves further (pre)clinical investigations as a candidate anti-HIV drug.

  15. Synthesis, spectral and antimicrobial activity of Zn(II) complexes with Schiff bases derived from 2-hydrazino-5-[substituted phenyl]-1,3,4-thiadiazole and benzaldehyde/2-hydroxyacetophenone/indoline-2,3-dione

    NASA Astrophysics Data System (ADS)

    Singh, Ajay K.; Pandey, O. P.; Sengupta, S. K.

    2013-09-01

    Zn(II) complexes have been synthesized by reacting zinc acetate with Schiff bases derived from 2-hydrazino-5-[substituted phenyl]-1,3,4-thiadiazole and 2-hydroxyacetophenone/benzaldehyde/indoline-2,3-dione. All these complexes are soluble in DMF and DMSO; low molar conductance values indicate that they are non electrolytes. Elemental analyses suggest that the complexes have 1:2 metal to ligands stoichiometry of the types [ZnL2(H2O)2](L = monoanionic Schiff bases derived from 2-hydrazino-5-[substituted phenyl]-1,3,4-thiadiazole and 2-hydroxyacetophenone/indoline-2,3-dione) [ZnL2‧(OOCCH3)2(H2O)2](L‧ = neutral Schiff bases derived from 2-hydrazino-5-[substituted phenyl]-1,3,4-thiadiazole and benzaldehyde), and they were characterized by IR, 1H NMR, and 13C NMR. Particle sizes of synthesized compounds were measured with dynamic light scattering (DLS) analyser which indicates that particle diameter are of the range ca. 100-200 nm. All these Schiff bases and their complexes have also been screened for their antibacterial (Bacillus subtilis (B. subtilis), Escherichia coli (E. coli) and antifungal activities (Colletotrichum falcatum (C. falcatum), Aspergillus niger (A. niger), Fusarium oxysporium (F. oxysporium) Curvularia pallescence (C. pallescence). The antimicrobial activities have shown that upon complexation the activity increases.

  16. Synthesis, spectral and antimicrobial activity of Zn(II) complexes with Schiff bases derived from 2-hydrazino-5-[substituted phenyl]-1,3,4-thiadiazole and benzaldehyde/2-hydroxyacetophenone/indoline-2,3-dione.

    PubMed

    Singh, Ajay K; Pandey, O P; Sengupta, S K

    2013-09-01

    Zn(II) complexes have been synthesized by reacting zinc acetate with Schiff bases derived from 2-hydrazino-5-[substituted phenyl]-1,3,4-thiadiazole and 2-hydroxyacetophenone/benzaldehyde/indoline-2,3-dione. All these complexes are soluble in DMF and DMSO; low molar conductance values indicate that they are non electrolytes. Elemental analyses suggest that the complexes have 1:2 metal to ligands stoichiometry of the types [ZnL2(H2O)2](L=monoanionic Schiff bases derived from 2-hydrazino-5-[substituted phenyl]-1,3,4-thiadiazole and 2-hydroxyacetophenone/indoline-2,3-dione) [ZnL2(')(OOCCH3)2(H2O)2](L'=neutral Schiff bases derived from 2-hydrazino-5-[substituted phenyl]-1,3,4-thiadiazole and benzaldehyde), and they were characterized by IR, (1)H NMR, and (13)C NMR. Particle sizes of synthesized compounds were measured with dynamic light scattering (DLS) analyser which indicates that particle diameter are of the range ca. 100-200nm. All these Schiff bases and their complexes have also been screened for their antibacterial (Bacillus subtilis (B. subtilis), Escherichia coli (E. coli) and antifungal activities (Colletotrichum falcatum (C. falcatum), Aspergillus niger (A. niger), Fusarium oxysporium (F. oxysporium) Curvularia pallescence (C. pallescence). The antimicrobial activities have shown that upon complexation the activity increases.

  17. Synthesis, characterization and anticonvulsant activity evaluation of some 1,4-dihydropyridines and 3,5-(substituted)oxycarbonyl-1,4-dihydro-2,6-dimethyl-N-[2-(4-sulfamoylphenylamino)-acetyl]-4-(substituted)pyridines.

    PubMed

    Subudhi, Bharat Bhusan; Panda, Prasanna K; Swain, Sarada P; Sarangi, Priyambada

    2009-01-01

    A series of 3,5-(substituted)oxycarbonyl-1,4-dihydro-2,6-dimethyl-4-(substituted)pyridines (1a-j) were synthesized by Hantzsch method for pyridine synthesis. Treatment with chloroacetyl chloride produced N-(2-chloroacetyl)-3,5-(substituted)oxycarbonyl-1,4-dihydro-2,6-dimethyl-4-(substituted)pyridines (2a-e), which on further treatment with sulfanilamide resulted in 3,5-(substituted)oxycarbonyl-1,4-dihydro-2,6-dimethyl-N-[2-(4-sulfamoylphenylamino)-acetyl]-4-(substituted)pyridines (3a-e). The structures has been established on the basis of spectral (IR, 1H-NMR, mass) and elemental analysis. Compounds 1a-j and 3a-e (5 mg/kg and 10 mg/kg) were evaluated for their anticonvulsant effect against pentylenetetrazole-induced convulsions with diazepam (4 mg/kg) as the reference. Compounds 3a-e exhibited significant (p<0.01) anticonvulsant activity compared to the control.

  18. From C,N- and N,N-chelated chloroboranes to substituted 1H-2,1-benzazaboroles and 1H-pyrrolo[1,2-c][1,3,2]diazaborolidines: a straightforward route to five-membered rings containing the B-N or N-B-N moiety.

    PubMed

    Hejda, Martin; Lyčka, Antonín; Jambor, Roman; Růžička, Aleš; Dostál, Libor

    2014-09-07

    A set of 1H-2,1-benzazaboroles as B-N analogues of 1H-indene and a set of 1H-pyrrolo[1,2-c][1,3,2]diazaborolidines as B-N analogues of 1H-pyrrolizine were prepared via nucleophilic addition of selected alkyl(aryl)lithiums (MeLi, tBuLi or PhLi) to, via N→B intramolecular interactions, the activated imino C[double bond, length as m-dash]N functionality in the structure of C,N- or N,N-chelated chloroboranes. All compounds were characterized by elemental analysis and (1)H, (11)B, (13)C and (15)N NMR spectroscopy, and molecular structures of isolated compounds were on several occasions established by means of single-crystal X-ray diffraction analysis. The presence of three adjacently bonded substituents and their systematic alternation on five-membered C3BN (1H-2,1-benzazaboroles) or C2BN2 (1H-pyrrolo[1,2-c][1,3,2]diazaborolidines) rings allowed us to follow both the influence of the steric repulsion and limitations for the formation of respective annulated heterocyclic systems.

  19. High-level ab initio predictions for the ionization energies and heats of formation of five-membered-ring molecules: thiophene, furan, pyrrole, 1,3-cyclopentadiene, and borole, C4H4X/C4H4X+ (X = S, O, NH, CH2, and BH).

    PubMed

    Lo, Po-Kam; Lau, Kai-Chung

    2011-02-10

    The ionization energies (IEs) and heats of formation (ΔH°(f0)/ΔH°(f298)) for thiophene (C(4)H(4)S), furan (C(4)H(4)O), pyrrole (C(4)H(4)NH), 1,3-cyclopentadiene (C(4)H(4)CH(2)), and borole (C(4)H(4)BH) have been calculated by the wave function-based ab initio CCSD(T)/CBS approach, which involves the approximation to the complete basis set (CBS) limit at the coupled-cluster level with single and double excitations plus a quasi-perturbative triple excitation [CCSD(T)]. Where appropriate, the zero-point vibrational energy correction (ZPVE), the core-valence electronic correction (CV), and the scalar relativistic effect (SR) are included in these calculations. The respective CCSD(T)/CBS predictions for C(4)H(4)S, C(4)H(4)O, C(4)H(4)NH, and C(4)H(4)CH(2), being 8.888, 8.897, 8.222, and 8.582 eV, are in excellent agreement with the experimental values obtained from previous photoelectron and photoion measurements. The ΔH°(f0)/ΔH°(f298) values for the aforementioned molecules and their corresponding cations have also been predicted by the CCSD(T)/CBS method, and the results are compared with the available experimental data. The comparisons between the CCSD(T)/CBS predictions and the experimental values for C(4)H(4)S, C(4)H(4)O, C(4)H(4)NH, and C(4)H(4)CH(2) suggest that the CCSD(T)/CBS procedure is capable of predicting reliable IE values for five-membered-ring molecules with an uncertainty of ±13 meV. In view of the excellent agreements between the CCSD(T)/CBS predictions and the experimental values for C(4)H(4)S, C(4)H(4)O, C(4)H(4)NH, and C(4)H(4)CH(2), the similar CCSD(T)/CBS IE and ΔH°(f0)/ΔH°(f298) predictions for C(4)H(4)BH, whose thermochemical data are not readily available due to its reactive nature, should constitute a reliable data set. The CCSD(T)/CBS IE(C(4)H(4)BH) value is 8.868 eV, and ΔH°(f0)/ΔH°(f298) values for C(4)H(4)BH and C(4)H(4)BH(+) are 269.5/258.6 and 1125.1/1114.6 kJ/mol, respectively. The highest occupied molecular orbitals

  20. Synthesis and evaluation of a classical 2,4-diamino-5-substituted-furo[2,3-d]pyrimidine and a 2-amino-4-oxo-6-substituted-pyrrolo[2,3-d]pyrimidine as antifolates☆

    PubMed Central

    Gangjee, Aleem; Yang, Jie; McGuire, John J.; Kisliuk, Roy L.

    2013-01-01

    Two classical antifolates, a 2,4-diamino-5-substituted furo[2,3-d]pyrimidine and a 2-amino-4-oxo-6-substituted pyrrolo[2,3-d]pyrimidine, were synthesized as potential inhibitors of dihydrofolate reductase (DHFR) and thymidylate synthase (TS). The syntheses were accomplished by condensation of 2,6-diamino-3(H)-4-oxo-pyrimidine with α-chloro-ketone 21 to afford two key intermediates 23 and 24, followed by hydrolysis, coupling with l-glutamate diethyl ester and saponification of the diethyl ester to afford the classical antifolates 13 and 14. Compounds 13 and 14 with a single carbon atom bridge are both substrates for folylpoly-γ-glutamate synthetase (FPGS), the enzyme responsible for forming critical poly-γ-glutamate antifolate metabolites with increased potency and/or increased cell retention. Compound 14 is a highly efficient FPGS substrate demonstrating that 2,4-diamino-5-substituted furo[2,3-d]pyrimidines are important lead structures for the design of antifolates with FPGS substrate activity. It retains inhibitory potency for DHFR and TS compared to the two atom bridged analog 5. Compound 13 is a poor inhibitor of purified DHFR and TS, and both 13 and 14 are poor inhibitors of the growth of CCRF-CEM human leukemia cells in culture, indicating that single carbon bridged compounds in these series though conducive to FPGS substrate activity were not potent inhibitors. PMID:16990006

  1. [Synthesis and antibacterial activity of 3-(5-substituted phenyl-[1,3,4] oxadiazole-2-yl-methylenethio)-5-pyridin-3-yl-[1,2,4] triazole-4-yl-amines].

    PubMed

    Hu, Guo-qiang; Xie, Song-qiang; Xu, Qiu-ju; Huang, Wen-long; Zhang, Hui-bin; Huang, Sheng-tang

    2005-04-01

    To study on synthesis and antibacterial activity evaluation of polyheterocycles. The condensation of 4-amino-3-pyridin-3-yl-4H-[1,2,4] triazole-5-thiol with 2-chloromethyl-5-substituted phenyl-[1,3,4] oxadiazoles gave the corresponding title heterocycle amines, and the in vitro antibacterial activity was primarily evaluated by the method of cup-plate diffusion solution. Twelve novel compounds were synthesized, and their structures were confirmed by IR, 1H NMR, MS and element analysis. Biological screening results demonstrated that most of the compounds prepared showed good antibacterial activity. Oxadiazoles incorporting pyridyl triazole ring may be a pharmacophor structure in the molecule for developing antibacterial candidate drugs.

  2. Synthesis and biological activity of novel series of 4-methoxy, and 4,9-dimethoxy-5-substituted furo[2,3-g]-1,2,3-benzoxathiazine-7,7-dioxide derivatives

    PubMed Central

    El-Sawy, Eslam R.; Ebaid, Manal S.; Abo-Salem, Heba M.; El-Hallouty, Salwa; Kassem, Emad M.; Mandour, Adel H.

    2013-01-01

    A novel series of 4-methoxy, and 4,9-dimethoxy-5-substituted furo[2,3-g]-1,2,3-benzoxathiazine-7,7-dioxide derivatives 3a,b, 10a–g and 11a–g were prepared in good yields via the reaction of 4-methoxy (1a) and 4,7-dimethoxy-5-acetyl-6-hydroxybenzofurans (1b) and their α,β-unsaturated keto derivatives 6a–g and 7a–g with chlorosulfonyl isocyanate (CSI). On the other hand, N-chlorosulfonyl carbamate derivatives 4a,b, 12a,b and 13a,b were prepared and allowed to react with piperidine to give the corresponding N-piperidinosulfonyl carbamate derivatives 5a,b, 14a,b and 15a,b, respectively. Sixteen new target compounds 3a,b, 10a–g, and 11a–g were tested for their DPPH radical-scavenging, and in vitro antiproliferative activity against A-549, MCF7 and HCT-116 cancer cell lines. Compounds 10a, 11c, 11e, and 11g showed moderate DPPH radical-scavenging activity compared to ascorbic acid at 100 μg/mL. 4,9-Dimethoxy-5-substituted styrylfuro[3,2-g]-1,2,3-benzoxathiazine-7,7-dioxides 11a, 11b, and 11c were found to be highly active against A-549 and HCT-116 cancer cell lines with IC50 values ranging from 0.02 to 0.08 μmol/mL compared to doxorubicin with IC50 = 0.04 and 0.06 μmol/mL, respectively. PMID:25685501

  3. Synthesis of C-5 Substituted Tubercidin Derivatives.

    DTIC Science & Technology

    1980-06-01

    2 invoked bromination of 4- chloro -7-( 2 ’, 3 ’,5’-tri-O-acetyl-r-D-ribofuranosyl)pyrrolo- [2,3...Gerster, J.F.; Robins, R.K.; Townsend, L.B. J. Heterocyclic Chem. 1969, 6, 215-21. 6. 4- Chloro -7-( 2 ’, 3 ’,5’-tri-O-acetyl--D-ribofuranosyl)pyrrolo[2,3-d...3,3,3-Trifluoropropenyl )tubercidin .. .. ... ........ 2 C. 5-( 3 -Aaninopropyl)tubercidin .. .. ... ..... .... ... 2 D.

  4. Mononuclear copper(II) complexes with 3,5-substituted-4-salicylidene-amino-3,5-dimethyl-1,2,4-triazole: synthesis, structure and potent inhibition of protein tyrosine phosphatases.

    PubMed

    Ma, Ling; Lu, Liping; Zhu, Miaoli; Wang, Qingming; Li, Ying; Xing, Shu; Fu, Xueqi; Gao, Zengqiang; Dong, Yuhui

    2011-06-28

    Six copper complexes of Schiff base ligands containing 3,5-substituted-4-salicylideneamino-3,5-dimethyl-1,2,4-triazole have been synthesized and well characterized. The structures of complexes 1 and 2 were determined by X-ray crystal analysis. Fluorescence and potentiometric study indicated that in the physiological pH range, one ligand was dissociated from the complexes to form 1:1 mononucleus copper complexes. The complexes potently inhibit protein tyrosine phosphatase 1B (PTP1B), T-cell protein tyrosine phosphatase (TCPTP), megakaryocyte protein tyrosine phosphatase 2 (PTP-MEG2) and Src homology phosphatase 1 (SHP-1) with 3-4 fold selectivity against PTP1B over TCPTP and PTP-MEG2, and 3-9 fold over SHP-1, but display almost no inhibition against Src homology phosphatase 2 (SHP-2). Complex 1 inhibits PTP1B with a competitive model with K(i) of 30 nM. Substitution with small groups at the phenyl of the ligand does not obviously influence the inhibitory ability of the complexes.

  5. N2 elimination thermolysis reactions of 9-(4- and 5-substituted-1,2,3-triazol-1-yl)acridines to produce 1H-pyrido-[4,3,2-kl] derivatives - A theoretical study

    NASA Astrophysics Data System (ADS)

    Taherpour, Avat (Arman); Ghasemhezaveh, Fatemeh; Yari, Ako; Khodaei, Mohammad Mehdi

    2017-05-01

    9-azidoacridine reacts under 1,3-dipolar reaction with alkyne derivatives to yield 9-(4- and 5-substituted-1,2,3-triazol-1-yl)acridine derivatives. The extrusion of N2 from these compounds leads to formation of carbene and biradical intermediates. Radical moieties interact with the acridine ring to form 1H-pyrido-[4,3,2-kl] derivatives. The focus of this study was on the theoretical and computational studies of the pathways of the products. The energy levels of the reactant species, TS forms (transition states), products, the free energies of reaction (ΔrG and ΔG#), HOMO & LUMO orbital levels, the ΔEHOMO-LUMO, dipolmoments, rate constants by using Eyring's equation (k and k‧), structural data were calculated by DFT (B3LYP/6-31G∗) method. The relative energies (in kcal mol-1) of the transition states as well as the biradical (singlet (S) and triplet (T); and carbene (singlet (S) and triplet (T); intermediates of the pyrolysis reactions on the reactants were investigated as well. The stepwise of the N2 elimination reactions have also investigated. The values of the free activation energy (ΔG#) in the concerted N2 elimination pyrolysis reactions were correlated to the decomposition temperature (TDecom.) of reactants.

  6. The Effect of Electrostatic Interactions on Conformational Equilibria of Multiply-Substituted Tetrahydropyran Oxocarbenium Ions

    PubMed Central

    Yang, Michael T.; Woerpel, K. A.

    2009-01-01

    The three-dimensional structures of dioxocarbenium ions related to glycosyl cations were determined by an analysis of spectroscopic, computational, and reactivity data. Hypothetical low-energy structures of the dioxocarbenium ions were correlated with both experimentally determined 1H NMR coupling constants and diastereoselectivity results from nucleophilic substitution reactions. This method confirmed the pseudoaxial preference of C-3 alkoxy-substituted systems and revealed the conformational preference of the C-5 alkoxymethyl group. Although the monosubstituted C-5 alkoxymethyl substituent preferred a pseudoequatorial orientation, the C-5–C-6 bond rotation was controlled by an electrostatic effect. The preferred diaxial conformer of the trans-4,5-disubstituted tetrahydropyranyl system underscored the importance of electrostatic effects in dictating conformational equilibria. In the 2-deoxymannose system, although steric effects influenced the orientation of the C-5 alkoxymethyl substituent, the all-axial conformer was favored because of electrostatic stabilization. PMID:19072093

  7. Five-Membered Ring Peroxide Selectively Initiates Ferroptosis in Cancer Cells.

    PubMed

    Abrams, Rachel P; Carroll, William L; Woerpel, K A

    2016-05-20

    A 1,2-dioxolane (FINO2) was identified as a lead compound from a screen of organic peroxides. FINO2 does not induce apoptosis, but instead initiates ferroptosis, an iron-dependent, oxidative cell death pathway. Few compounds are known to induce primarily ferroptosis. In contrast to the perceived instability of peroxides, FINO2 was found to be thermally stable to at least 150 °C. FINO2 was more potent in cancer cells than nonmalignant cells of the same type. One of the enantiomers was found to be more responsible for the observed activity.

  8. Palladium-Catalyzed Amination of Unprotected Five-Membered Heterocyclic Bromides

    PubMed Central

    2015-01-01

    An efficient method for the palladium-catalyzed amination of unprotected bromoimidazoles and bromopyrazoles is presented. The transformation is facilitated by the use of our newly developed Pd precatalyst based on the bulky biarylphosphine ligand tBuBrettPhos (L4). The mild reaction conditions employed allow for the preparation of a broad scope of aminoimidazoles and aminopyrazoles in moderate to excellent yields. PMID:24417224

  9. Palladium-catalyzed amination of unprotected five-membered heterocyclic bromides.

    PubMed

    Su, Mingjuan; Hoshiya, Naoyuki; Buchwald, Stephen L

    2014-02-07

    An efficient method for the palladium-catalyzed amination of unprotected bromoimidazoles and bromopyrazoles is presented. The transformation is facilitated by the use of our newly developed Pd precatalyst based on the bulky biarylphosphine ligand tBuBrettPhos (L4). The mild reaction conditions employed allow for the preparation of a broad scope of aminoimidazoles and aminopyrazoles in moderate to excellent yields.

  10. Amino acids and peptides activate at least five members of the human bitter taste receptor family.

    PubMed

    Kohl, Susann; Behrens, Maik; Dunkel, Andreas; Hofmann, Thomas; Meyerhof, Wolfgang

    2013-01-09

    Amino acids and peptides represent important flavor molecules eliciting various taste sensations. Here, we present a comprehensive assessment of the interaction of various peptides and all proteinogenic amino acids with the 25 human TAS2Rs expressed in cell lines. L-Phenylalanine and L-tryptophan activate TAS2R1 and TAS2R4, respectively, whereas TAS2R4 and TAS2R39 responded to D-tryptophan. Structure-function analysis uncovered the basis for the lack of stereoselectivity of TAS2R4. The same three TAS2Rs or subsets thereof were also sensitive to various dipeptides containing L-tryptophan, L-phenylalanine, or L-leucine and to Trp-Trp-Trp, whereas Leu-Leu-Leu specifically activated TAS2R4. Trp-Trp-Trp also activated TAS2R46 and TAS2R14. Two key bitter peptides from Gouda cheese, namely, Tyr-Pro-Phe-Pro-Gly-Pro-Ile-His-Asn-Ser and Leu-Val-Tyr-Pro-Phe-Pro-Gly-Pro-Ile-His-Asn, both activated TAS2R1 and TAS2R39. Thus, the data demonstrate that the bitterness of amino acids and peptides is not mediated by specifically tuned TAS2Rs but rather is brought about by an unexpectedly complex pattern of sensitive TAS2Rs.

  11. A five-membered lactone prodrug of CBI-based analogs of the duocarmycins

    PubMed Central

    Uematsu, Mika; Brody, Daniel M.; Boger, Dale L.

    2014-01-01

    The preparation, characterization and examination of the CBI-based 5-membered lactone 5 capable of serving as a prodrug or protein (antibody) conjugation reagent are disclosed along with its incorporation into the corresponding CC-1065 and duocarmycin analog 6, and the establishment of their properties. PMID:26069351

  12. Five-membered heterocycles. Part IV: Impact of heteroatom on benzazole aromaticity

    NASA Astrophysics Data System (ADS)

    Karolak-Wojciechowska, J.; Mrozek, A.; Czylkowski, R.; Tekiner-Gulbas, B.; Akı-Şener, E.; Yalçin, I.

    2007-08-01

    To complete a set of 3-D data for phenoxymethyl-benzazoles, molecular structures of respective benzothiazole and benzimidazole were determined using X-ray crystallography. Based on that, the structure and conformation of the benzazole bicycle (6 + 5) with various heteroatoms in position 3 - nitrogen, sulphur or oxygen - are discussed. Subsequently, aromaticity of (6 + 5) bicycles was analyzed on the basis of crystallographic data (our and from CSD) and HOMA index, quantitative estimation of heteroring aromaticity, was calculated. The rings aromaticity is amplified from oxygen to sulphur and nitrogen as the second heteroatom. The dependences between HOMA av indices and respective heteroatom electronegativity were roughly established as second-degree polynomial with maximum in the vicinity of nitrogen. Similar relationship was found between HOMA av and lipophilicity descriptor log D (at pH 7.4) for phenoxymethyl-benzoxazole, -benzothiazole, -benzimidazole. Both relationships explain the categorization of the species with various Y according to the location in periodic table of the elements.

  13. The improved syntheses of 5-substituted 2'-[18F]fluoro-2'-deoxy-arabinofuranosyluracil derivatives ([18F]FAU, [18F]FEAU, [18F]FFAU, [18F]FCAU, [18F]FBAU and [18F]FIAU) using a multistep one-pot strategy.

    PubMed

    Cai, Hancheng; Li, Zibo; Conti, Peter S

    2011-07-01

    We and others have previously reported a four-step radiosynthesis of a series of 2'-deoxy-2'-[(18)F]fluoro-5-substituted-1-β-D-arabinofuranosyluracil derivatives including [(18)F]FAU, [(18)F]FEAU, [(18)F]FFAU, [(18)F]FCAU, [(18)F]FBAU and [(18)F]FIAU as thymidine derivatives for tumor proliferation and/or reporter gene expression imaging with positron emission tomography (PET). Although the radiosynthesis has been proven to be reproducible and efficient, this complicated multistep reaction is difficult to incorporate into an automated cGMP-compliant radiosynthesis module for routine production. Recently, we have developed a simple and efficient one-pot method for routine production of [(18)F]FMAU. In this study, we studied the feasibility of radiosynthesizing [(18)F]FAU, [(18)F]FEAU, [(18)F]FFAU, [(18)F]FCAU, [(18)F]FBAU and [(18)F]FIAU using this newly developed method. Similar to the radiosynthesis of [(18)F]FMAU, 5-substituted 2'-[(18)F]fluoro-2'-deoxy-arabinofuranosyluracil derivatives ([(18)F]FAU, [(18)F]FEAU, [(18)F]FFAU, [(18)F]FCAU, [(18)F]FBAU and [(18)F]FIAU) were synthesized in one-pot radiosynthesis module in the presence of Friedel-Crafts catalyst TMSOTf and HMDS. This one-pot radiosynthesis method could be used to produce [(18)F]FAU, [(18)F]FEAU, [(18)F]FFAU, [(18)F]FCAU, [(18)F]FBAU and [(18)F]FIAU. The overall radiochemical yields of these tracers varied from 4.1%±0.8% to 10.1%±1.9% (decay-corrected, n=4). The overall reaction time was reduced from 210 min to 150 min from the end of bombardment, and the radiochemical purity was >99%. The improved radiosyntheses of [(18)F]FAU, [(18)F]FEAU, [(18)F]FFAU, [(18)F]FCAU, [(18)F]FBAU and [(18)F]FIAU have been achieved with reasonable yields and high purity using a multistep one-pot method. The synthetic time has been reduced, and the reaction procedures have been significantly simplified. The success of this approach may make PET tracers [(18)F]FAU, [(18)F]FEAU, [(18)F]FFAU, [(18)F]FCAU, [(18)F]FBAU and

  14. 5-substituted derivatives of 6-halogeno-3-((2-(S)-azetidinyl)methoxy)pyridine and 6-halogeno-3-((2-(S)-pyrrolidinyl)methoxy)pyridine with low picomolar affinity for alpha4beta2 nicotinic acetylcholine receptor and wide range of lipophilicity: potential probes for imaging with positron emission tomography.

    PubMed

    Zhang, Yi; Pavlova, Olga A; Chefer, Svetlana I; Hall, Andrew W; Kurian, Varughese; Brown, LaVerne L; Kimes, Alane S; Mukhin, Alexey G; Horti, Andrew G

    2004-05-06

    Potential positron emission tomography (PET) ligands with low picomolar affinity at the nicotinic acetylcholine receptor (nAChR) and with lipophilicity (log D) ranging from -1.6 to +1.5 have been synthesized. Most members of the series, which are derivatives of 5-substituted-6-halogeno-A-85380, exhibited a higher binding affinity at alpha4beta2-nAChRs than epibatidine. An analysis, by molecular modeling, revealed an important role of the orientation of the additional heterocyclic ring on the binding affinity of the ligands with nAChRs. The existing nicotinic pharmacophore models do not accommodate this finding. Two compounds of the series, 6-[(18)F]fluoro-5-(pyridin-3-yl)-A-85380 ([(18)F]31) and 6-chloro-3-((2-(S)-azetidinyl)methoxy)-5-(2-[(18)F]fluoropyridin-5-yl)pyridine) ([(18)F]35), were radiolabeled with (18)F. Comparison of PET data for [(18)F]31 and 2-[(18)F]FA shows the influence of lipophilicity on the binding potential. Our recent PET studies with [(18)F]35 demonstrated that its binding potential values in Rhesus monkey brain were ca. 2.5 times those of 2-[(18)F]FA. Therefore, [(18)F]35 and several other members of the series, when radiolabeled, will be suitable for quantitative imaging of extrathalamic nAChRs.

  15. The influence of sulfur configuration in (1) H NMR chemical shifts of diasteromeric five-membered cyclic sulfites.

    PubMed

    Obregón-Mendoza, Marco A; Sánchez-Castellanos, Mariano; Cuevas, Gabriel; Gnecco, Dino; Cassani, Julia; Poveda-Jaramillo, Juan C; Reynolds, William F; Enríquez, Raúl G

    2017-03-01

    The effect of the stereochemistry of the sulfur atom on (1) H chemical shifts of the diasteromeric pair of cyclic sulfites of 4-[methoxy(4-nitrophenyl)methyl]-5-phenyl-1,3,2-dioxathiolan-2-oxide was investigated. The complete (1) H and (13) C NMR spectral assignment was achieved by the use of one-dimensional and two-dimensional NMR techniques in combination with X-ray data. A correlation of experimental data with theoretical calculations of chemical shift tensors using density functional theory and topological theory of atoms in molecules was made. Copyright © 2016 John Wiley & Sons, Ltd.

  16. Stabilities and structures in cluster ions of five-membered heterocyclic compounds containing O, N, and S atoms

    SciTech Connect

    Hiraoka, K.; Takimoto, H.; Yamabe, S.

    1987-11-25

    Clustering and hydration reactions of protonated and radical cations of heterocyclic compounds, e.g., furan, tetrahydrofuran, pyrrole, pyrrolidine, thiophene, and tetrahydrothiophene, have been studied using a pulsed electron beam mass spectrometer. The bond energies of proton-held dimer cations for furan, pyrrole, and thiophene are much smaller than those for tetrahydrofuran, pyrrolidine, and tetrahydrothiophene, respectively. This result suggests that not the heteroatoms but the ..cap alpha.. carbon atoms are protonated for furan, pyrrole, and thiophene. The hydrogen-bond site for the protonated furan and thiophene is calculated to be the unprotonated ..cap alpha.. hydrogen (C-H/sub ..cap alpha../ adjacent to the heteroatom) which is the most acidic one. On the other hand, the N-H hydrogen is the best hydrogen-bond site for the protonated pyrrole. It was found that the radical-cations dimers have greater bond energies than the proton-held dimer cations for furan and thiophene. This suggests that the bonds of the former have more covalent nature. Some unique reactions of C/sub 4/H/sub 4/O/sup .+/ and C/sub 4/H/sub 5/O/sup +/ with a furan molecule were observed. With an increase of temperature, the ions with m/z which are the same as those for (C/sub 4/H/sub 4/O)/sub 2//sup .+/ and H/sup +/(C/sub 4/H/sub 4/O)/sub 2/ are found to be formed at the expense of C/sup 4/H/sub 4/O/sup .+/ and C/sub 4/H/sub 5/O/sup +/ ions, respectively. It is suggested that the reactions observed are Diels-Alder type condensation reactions.

  17. Azaphenalene phthalocyanines: phthalocyanine analogues with six-membered-ring units instead of five-membered-ring units.

    PubMed

    Shimizu, Soji; Zhu, Hua; Kobayashi, Nagao

    2010-09-24

    Mixed-condensation reaction of 1,8-naphthalenedicarbonitrile and a 4,5-disubstituted phthalonitrile provided a series of phthalocyanine (Pc) analogues with azaphenalene (AP) moieties in place of the isoindole moieties. Monosubstituted species, APPc, and the two structural isomers of disubstituted species, adj-AP(2)Pc and opp-AP(2)Pc, were successfully isolated by gel-permeation chromatography on HPLC apparatus. Their structures were elucidated by (1)H NMR spectroscopy and X-ray crystallographic analysis. Replacement of the isoindole moieties with azaphenalene moieties created six-membered-ring units in the core and caused distortion of the molecular structures. The Q-band absorption shifted to the red upon an increase in the number of azaphenalene units; the shape of the absorption spectra depended on the molecular symmetries. APPc and opp-AP(2)Pc showed a large splitting of the Q band, whereas adj-AP(2)Pc exhibited a single broad Q band. These changes in the absorption spectra, as well as the unique electronic structures, are discussed in detail, based on magnetic circular dichroism spectra, electrochemical measurements, and density functional theory calculations.

  18. Phylogenetic and ecological patterns in nighttime transpiration among five members of the genus Rubus co-occurring in western Oregon

    PubMed Central

    McNellis, Brandon; Howard, Ava R

    2015-01-01

    Nighttime transpiration is a substantial portion of ecosystem water budgets, but few studies compare water use of closely related co-occurring species in a phylogenetic context. Nighttime transpiration can range up to 69% of daytime rates and vary between species, ecosystem, and functional type. We examined leaf-level daytime and nighttime gas exchange of five species of the genus Rubus co-occurring in the Pacific Northwest of western North America in a greenhouse common garden. Contrary to expectations, nighttime transpiration was not correlated to daytime water use. Nighttime transpiration showed pronounced phylogenetic signals, but the proportion of variation explained by different phylogenetic groupings varied across datasets. Leaf osmotic water potential, water potential at turgor loss point, stomatal size, and specific leaf area were correlated with phylogeny but did not readily explain variation in nighttime transpiration. Patterns in interspecific variation as well as a disconnect between rates of daytime and nighttime transpiration suggest that variation in nighttime water use may be at least partly driven by genetic factors independent of those that control daytime water use. Future work with co-occurring congeneric systems is needed to establish the generality of these results and may help determine the mechanism driving interspecific variation in nighttime water use. PMID:26380686

  19. Phylogenetic and ecological patterns in nighttime transpiration among five members of the genus Rubus co-occurring in western Oregon.

    PubMed

    McNellis, Brandon; Howard, Ava R

    2015-09-01

    Nighttime transpiration is a substantial portion of ecosystem water budgets, but few studies compare water use of closely related co-occurring species in a phylogenetic context. Nighttime transpiration can range up to 69% of daytime rates and vary between species, ecosystem, and functional type. We examined leaf-level daytime and nighttime gas exchange of five species of the genus Rubus co-occurring in the Pacific Northwest of western North America in a greenhouse common garden. Contrary to expectations, nighttime transpiration was not correlated to daytime water use. Nighttime transpiration showed pronounced phylogenetic signals, but the proportion of variation explained by different phylogenetic groupings varied across datasets. Leaf osmotic water potential, water potential at turgor loss point, stomatal size, and specific leaf area were correlated with phylogeny but did not readily explain variation in nighttime transpiration. Patterns in interspecific variation as well as a disconnect between rates of daytime and nighttime transpiration suggest that variation in nighttime water use may be at least partly driven by genetic factors independent of those that control daytime water use. Future work with co-occurring congeneric systems is needed to establish the generality of these results and may help determine the mechanism driving interspecific variation in nighttime water use.

  20. A New Strategy for Enantioselective Construction of Multisubstituted Five-Membered Oxygen Heterocycles via a Domino Michael/Hemiketalization Reaction.

    PubMed

    Hua, Yuan-Zhao; Liu, Meng-Meng; Huang, Pei-Jin; Song, Xixi; Wang, Min-Can; Chang, Jun-Biao

    2015-08-17

    A new highly enantioselective domino Michael/hemiketalization reaction of α-hydroxyacetophenone with β,γ-unsaturated α-keto esters for the synthesis of 2,2,4,5-tetrasubstituted chiral tetrahydrofurans is reported. With 2 mol % intramolecular dinuclear zinc-AzePhenol complex prepared in situ from the reaction of multidentate semi-azacrown ether ligand with ZnEt2 , the corresponding anti-multisubstituted tetrahydrofuran products were obtained in up to 90 % yields, and 98 % enantiomeric excess (ee) at 0 °C for 45 min. Moreover, the products were easily converted to 2,3,5-trisubstituted 2,3-dihydrofurans without any loss in optical activity. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Preferential selection of isomer binding from chiral mixtures: alternate binding modes observed for the E and Z isomers of a series of 5-substituted 2,4-­diaminofuro[2,3-d]pyrimidines as ternary complexes with NADPH and human dihydrofolate reductase

    PubMed Central

    Cody, Vivian; Piraino, Jennifer; Pace, Jim; Li, Wei; Gangjee, Aleem

    2010-01-01

    The crystal structures of six human dihydrofolate reductase (hDHFR) ternary complexes with NADPH and a series of mixed E/Z isomers of 5-substituted 5-[2-(2-methoxyphenyl)-prop-1-en-1-yl]furo[2,3-d]pyrimidine-2,4-diamines substituted at the C9 position with propyl, isopropyl, cyclopropyl, butyl, isobutyl and sec-butyl (E2–E7, Z3) were determined and the results were compared with the resolved E and Z isomers of the C9-methyl parent compound. The configuration of all of the inhibitors, save one, was observed as the E isomer, in which the binding of the furopyrimidine ring is flipped such that the 4-­amino group binds in the 4-oxo site of folate. The Z3 isomer of the C9-isopropyl analog has the normal 2,4-diamino­pyrimidine ring binding geometry, with the furo oxygen near Glu30 and the 4-amino group interacting near the cofactor nicotinamide ring. Electron-density maps for these structures revealed the binding of only one isomer to hDHFR, despite the fact that chiral mixtures (E:Z ratios of 2:1, 3:1 and 3:2) of the inhibitors were incubated with hDHFR prior to crystallization. Superposition of the hDHFR com­plexes with E2 and Z3 shows that the 2′-methoxyphenyl ring of E2 is perpendicular to that of Z3. The most potent inhibitor in this series is the isopropyl analog Z3 and the least potent is the isobutyl analog E6, consistent with data that show that the Z isomer makes the most favorable interactions with the active-site residues. The isobutyl moiety of E6 is observed in two orientations and the resultant steric crowding of the E6 analog is consistent with its weaker activity. The alternative binding modes observed for the furopyrimidine ring in these E/Z isomers suggest that new templates can be designed to probe these binding regions of the DHFR active site. PMID:21123866

  2. High 1,3-trans stereoselectivity in nucleophilic substitution at the anomeric position and β-fragmentation of the primary alkoxyl radical in 3-amino-3-deoxy-ribofuranose derivatives: application to the synthesis of 2-epi-(-)-jaspine B.

    PubMed

    Sánchez-Eleuterio, Alma; Quintero, Leticia; Sartillo-Piscil, Fernando

    2011-07-01

    The high inverse stereoselectivity in the nucleophilic substitution at the anomeric position of 3-amino-3-deoxy-ribofuranose derivatives is reported. This unprecedented stereoselectivity is explained in terms of preferential nucleophilic attack on the "inside face" of the respective five-membered ring oxocarbenium ion that orients pseudoequatorially to the benzylamine group placed at the C-3 position. In addition, an unusual β-fragmentation of a primary alkoxyl radical generated from its corresponding N-phthalimide derivative was achieved, and thus taking advantages of both reactions, the total synthesis of 2-epi-(-)-jaspine B was completed.

  3. Epitaxial growth and magnetic properties of the first five members of the layered Srn +1RunO3n+1 oxide series

    NASA Astrophysics Data System (ADS)

    Tian, W.; Haeni, J. H.; Schlom, D. G.; Hutchinson, E.; Sheu, B. L.; Rosario, M. M.; Schiffer, P.; Liu, Y.; Zurbuchen, M. A.; Pan, X. Q.

    2007-01-01

    Epitaxial thin films of the n =1-5 members of the layered Srn +1RunO3n+1 oxide series were produced by reactive molecular-beam epitaxy. X-ray diffraction and high-resolution transmission electron microscopy confirm that these films are epitaxially oriented and nearly phase pure (>98%). The Sr2RuO4 (n=1) and Sr3Ru2O7 (n=2) samples show no ferromagnetic transition in the range from 5to300K, while the Sr4Ru3O10 (n=3), Sr5Ru4O13 (n=4), and Sr6Ru5O16 (n=5) samples show ferromagnetic transitions at 85, 95, and 130K, respectively.

  4. Five-membered arsenic-sulfur-nitrogen heterocycles, RAs(S2N2) (R = Me, Et, (i)Pr, (t)Bu, Ph, Mes).

    PubMed

    Matuska, Vit; Slawin, Alexandra M Z; Woollins, J Derek

    2010-03-15

    A series of 5-alkyl/aryl-1,3lambda(4)delta(2),2,4,5-dithiadiazarsoles RAs(S(2)N(2)) (R = Me, Et, (i)Pr, (t)Bu, Ph, Mes) were prepared by a ligand exchange between [(n)Bu(2)Sn(S(2)N(2))](2) and the corresponding organodihalogenoarsines RAsX(2) (X = Cl, I). All products were characterized by NMR, IR, and Raman spectroscopies and mass spectrometry. The crystal structures of the aryldithiadiazarsoles (R = Ph, Mes) were determined.

  5. Kinetics and functional diversity among the five members of the NADP-malic enzyme family from Zea mays, a C4 species.

    PubMed

    Alvarez, Clarisa E; Saigo, Mariana; Margarit, Ezequiel; Andreo, Carlos S; Drincovich, María F

    2013-05-01

    NADP-malic enzyme (NADP-ME) is involved in different metabolic pathways in several organisms due to the relevant physiological functions of the substrates and products of its reaction. In plants, it is one of the most important proteins that were recruited to fulfil key roles in C4 photosynthesis. Recent advances in genomics allowed the characterization of the complete set of NADP-ME genes from some C3 species, as Arabidopsis thaliana and Oryza sativa; however, the characterization of the complete NADP-ME family from a C4 species has not been performed yet. In this study, while taking advantage of the complete Zea mays genome sequence recently released, the characterization of the whole NADP-ME family is presented. The maize NADP-ME family is composed of five genes, two encoding plastidic NADP-MEs (ZmC4- and ZmnonC4-NADP-ME), and three cytosolic enzymes (Zmcyt1-, Zmcyt2-, and Zmcyt3-NADP-ME). The results presented clearly show that each maize NADP-ME displays particular organ distribution, response to stress stimuli, and differential biochemical properties. Phylogenetic footprinting studies performed with the NADP-MEs from several grasses, indicate that four members of the maize NADP-ME family share conserved transcription factor binding motifs with their orthologs, indicating conserved physiological functions for these genes in monocots. Based on the results obtained in this study, and considering the biochemical plasticity shown by the NADP-ME, it is discussed the relevance of the presence of a multigene family, in which each member encodes an isoform with particular biochemical properties, in the evolution of the C4 NADP-ME, improved to fulfil the requirements for an efficient C4 mechanism.

  6. The oxytocin/vasopressin receptor family has at least five members in the gnathostome lineage, inclucing two distinct V2 subtypes.

    PubMed

    Ocampo Daza, Daniel; Lewicka, Michalina; Larhammar, Dan

    2012-01-01

    The vertebrate oxytocin and vasopressin receptors form a family of G-protein-coupled receptors (GPCRs) that mediate a large variety of functions, including social behavior and the regulation of blood pressure, water balance and reproduction. In mammals four family members have been identified, three of which respond to vasopressin (VP) named V1A, V1B and V2, and one of which is activated by oxytocin (OT), called the OT receptor. Four receptors have been identified in chicken as well, but these have received different names. Until recently only V1-type receptors have been described in several species of teleost fishes. We have identified family members in several gnathostome genomes and performed phylogenetic analyses to classify OT/VP-receptors across species and determine orthology relationships. Our phylogenetic tree identifies five distinct ancestral gnathostome receptor subtypes in the OT/VP receptor family: V1A, V1B, V2A, V2B and OT receptors. The existence of distinct V2A and V2B receptors has not been previously recognized. We have found these two subtypes in all examined teleost genomes as well as in available frog and lizard genomes and conclude that the V2A-type is orthologous to mammalian V2 receptors whereas the V2B-type is orthologous to avian V2 receptors. Some teleost fishes have acquired additional and more recent gene duplicates with up to eight receptor family members. Thus, this analysis reveals an unprecedented complexity in the gnathostome repertoire of OT/VP receptors, opening interesting research avenues regarding functions such as regulation of water balance, reproduction and behavior, particularly in reptiles, amphibians, teleost fishes and cartilaginous fishes. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Coordination as a best practice from the polio eradication initiative: Experiences from five member states in the African region of the World Health Organization.

    PubMed

    Okeibunor, Joseph; Nsubuga, Peter; Salla, Mbaye; Mihigo, Richard; Mkanda, Pascal

    2016-10-10

    As part of the efforts to eradicate polioviruses in the African Region, structures were put in place to ensure coordinated mobilization and deployment of resources within the framework of the global polio eradication initiative (PEI). The successes of these structures made them not only attractive to other public health interventions, but also caused them to be deployed to the response efforts of other diseases interventions, without any systematic documentation. This article documents the contributions of PEI coordination units to other public health interventions in the African Region of World Health Organization METHODS: We reviewed the contributions of PEI coordination units to other public health interventions in five countries in the African Region. The analysis identified significant involvement of PEI coordination structures in the implementation of routine immunization programs in all the countries analyzed. Similarly, maternal and child health programs were planned, implemented, monitored and evaluation the Inter-Agency Coordination Committees of the PEI programs in the different countries. The hubs system used in PEI in Chad facilitated the efficient coordination of resources for immunization and other public health interventions in Chad. Similarly, in the Democratic Republic of Congo PEI led coordination activities benefited other public health programs like disease control and the national nutrition program, the national malaria control program, and the tuberculosis control program. In Nigeria, the polio Expert Review Committee effectively deployed the Emergency Operation Center for the implementation of prioritized strategies and activities of the National Polio Eradication Emergency Plan, and it was utilized in the response to Ebola Virus Disease outbreak in the country. The PEI-led coordination systems are thus recognized as having made significant contribution to the coordination and delivery of other public health interventions in the African Region. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. The effect of 5-substitution on the electrochemical behavior and antitubercular activity of PA-824

    PubMed Central

    Bollo, Soledad; Núñez-Vergara, Luis J.; Kang, Sunhee; Zhang, Liang; Boshoff, Helena I.; Barry, Clifton E.; Squella, Juan A.; Dowd, Cynthia S.

    2011-01-01

    Nitroimidazole PA-824 is part of an exciting new class of compounds currently undergoing clinical evaluation as novel TB therapeutics. The recently elucidated mechanism of action of PA-824 involves reduction of the nitroimidazole ring and subsequent nitric oxide release. The importance of this compound and its unique activity prompted us to explore how substitution of the nitroimidazole ring would affect electrochemical reduction and antitubercular activity. We prepared analogs of PA-824 with bromo, chloro, cyano, and amino substituents in the 5-position of the aromatic ring. We found that substitution of the imidazole ring greatly influences reduction and the stability of the corresponding nitro radical anion. Further, the antitubercular activities of the bromo and chloro analogs may indicate that an alternate nitroreductase pathway within Mycobacterium tuberculosis exists. PMID:21168331

  9. The effect of 5-substitution on the electrochemical behavior and antitubercular activity of PA-824.

    PubMed

    Bollo, Soledad; Núñez-Vergara, Luis J; Kang, Sunhee; Zhang, Liang; Boshoff, Helena I; Barry, Clifton E; Squella, Juan A; Dowd, Cynthia S

    2011-01-15

    Nitroimidazole PA-824 is part of an exciting new class of compounds currently undergoing clinical evaluation as novel TB therapeutics. The recently elucidated mechanism of action of PA-824 involves reduction of the nitroimidazole ring and subsequent nitric oxide release. The importance of this compound and its unique activity prompted us to explore how substitution of the nitroimidazole ring would affect electrochemical reduction and antitubercular activity. We prepared analogs of PA-824 with bromo, chloro, cyano, and amino substituents in the 5-position of the aromatic ring. We found that substitution of the imidazole ring greatly influences reduction and the stability of the corresponding nitro radical anion. Further, the antitubercular activities of the bromo and chloro analogs may indicate that an alternate nitroreductase pathway within Mycobacterium tuberculosis exists. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. A comparative study of the thermal stability of oligodeoxyribonucleotides containing 5-substituted 2'-deoxyuridines.

    PubMed Central

    Ahmadian, M; Zhang, P; Bergstrom, D E

    1998-01-01

    Two series of modified oligonucleotides based on the self-complementary dodecamer d(CGCTAATTAGCG) were synthesized. The first contained the -C identical withCCH2R linker at C5 of deoxyuridine at position 4 (T*) of d(CGCT*AATTAGCG) and the second contained the -SR linker. The goal of the study was to evaluate and compare these two types of side chains for suitability as tethers for linking reporter groups to oligonucleotides. Our primary concern was how these tethers would effect duplex stability. The modified nucleosides were synthesized by palladium-mediated coupling reactions between the substituted alkyne and 5'-(4, 4'-dimethoxytrityl)-5-iodo-2'-deoxyuridine and between a disulfide and 5-chloromercurio-2'-deoxyuridine. The C5 deoxyuridine side chains evaluated included C identical with CCH3, C identical with CCH2NHC(O)CH3, C identical with CCH2N(CH3)2, C identical with CCH2N-HC(O)C5H4N, C identical with CCH2NHC(O)C10H15, SCH3, SC6H5 and SCH2CH2NHC(O)CH3. The nucleosides containing these substituents were incorporated into oligo-deoxyribonucleotides by standard phosphoramidite methodology. Melting studies demonstrated that the sequence containing the C identical with CCH3side chain had the highest T m value (59.1 degrees C) in comparison with the control sequence (T m = 55.2 degrees C) and that any additional substituent on C3 of the propynyl group lowered the T m value relative to propynyl. Nevertheless, even the most destabilizing substituent, adamantylcarbamoyl, yielded an oligodeoxyribonucleotide that dissociated with a T m of 54 degrees C, which is only 1.2 degrees C less than the control sequence. In contrast, the thioether substituents led to lower T m values, ranging from as low as 45.1 degrees C for SPh up to 52.2 degrees C for SMe. Replacing the methyl of the SMe substituent with a CH2CH2NHC(O)CH3 tether led to no further reduction in melting temperature. The T m value of the CH2CH2NHC(O)CH3-containing oligonucleotide was less than the natural sequence by 1.6 degrees C/substituent. This is sufficiently small that it is anticipated that the C5 thioether linkage may be as useful as the acetylenic linkage for tethering reporter groups to oligonucleotides. More importantly, the thioether linkage provides a means to position functional groups to interact specifically with opposing complementary (target) sequences. PMID:9628909

  11. A comparative study of the thermal stability of oligodeoxyribonucleotides containing 5-substituted 2'-deoxyuridines.

    PubMed

    Ahmadian, M; Zhang, P; Bergstrom, D E

    1998-07-01

    Two series of modified oligonucleotides based on the self-complementary dodecamer d(CGCTAATTAGCG) were synthesized. The first contained the -C identical withCCH2R linker at C5 of deoxyuridine at position 4 (T*) of d(CGCT*AATTAGCG) and the second contained the -SR linker. The goal of the study was to evaluate and compare these two types of side chains for suitability as tethers for linking reporter groups to oligonucleotides. Our primary concern was how these tethers would effect duplex stability. The modified nucleosides were synthesized by palladium-mediated coupling reactions between the substituted alkyne and 5'-(4, 4'-dimethoxytrityl)-5-iodo-2'-deoxyuridine and between a disulfide and 5-chloromercurio-2'-deoxyuridine. The C5 deoxyuridine side chains evaluated included C identical with CCH3, C identical with CCH2NHC(O)CH3, C identical with CCH2N(CH3)2, C identical with CCH2N-HC(O)C5H4N, C identical with CCH2NHC(O)C10H15, SCH3, SC6H5 and SCH2CH2NHC(O)CH3. The nucleosides containing these substituents were incorporated into oligo-deoxyribonucleotides by standard phosphoramidite methodology. Melting studies demonstrated that the sequence containing the C identical with CCH3side chain had the highest T m value (59.1 degrees C) in comparison with the control sequence (T m = 55.2 degrees C) and that any additional substituent on C3 of the propynyl group lowered the T m value relative to propynyl. Nevertheless, even the most destabilizing substituent, adamantylcarbamoyl, yielded an oligodeoxyribonucleotide that dissociated with a T m of 54 degrees C, which is only 1.2 degrees C less than the control sequence. In contrast, the thioether substituents led to lower T m values, ranging from as low as 45.1 degrees C for SPh up to 52.2 degrees C for SMe. Replacing the methyl of the SMe substituent with a CH2CH2NHC(O)CH3 tether led to no further reduction in melting temperature. The T m value of the CH2CH2NHC(O)CH3-containing oligonucleotide was less than the natural sequence by 1.6 degrees C/substituent. This is sufficiently small that it is anticipated that the C5 thioether linkage may be as useful as the acetylenic linkage for tethering reporter groups to oligonucleotides. More importantly, the thioether linkage provides a means to position functional groups to interact specifically with opposing complementary (target) sequences.

  12. Activities of certain 5-substituted 4'-thiopyrimidine nucleosides against orthopoxvirus infections.

    PubMed

    Kern, Earl R; Prichard, Mark N; Quenelle, Debra C; Keith, Kathy A; Tiwari, Kamal N; Maddry, Joseph A; Secrist, John A

    2009-02-01

    As part of a program to identify new compounds that have activity against orthopoxviruses, a number of 4'-thionucleosides were synthesized and evaluated for their efficacies against vaccinia and cowpox viruses. Seven compounds that were active at about 1 microM against both viruses in human cells but that did not have significant toxicity were identified. The 5-iodo analog, 1-(2-deoxy-4-thio-beta-d-ribofuranosyl)-5-iodouracil (4'-thioIDU), was selected as a representative molecule; and this compound also inhibited viral DNA synthesis at less than 1 microM but only partially inhibited the replication of a recombinant vaccinia virus that lacked a thymidine kinase. This compound retained complete activity against cidofovir- and ST-246-resistant mutants. To determine if this analog had activity in an animal model, mice were infected intranasally with vaccinia or cowpox virus and treatment with 4'-thioIDU was given intraperitoneally or orally twice daily at 50, 15, 5, or 1.5 mg/kg of body weight beginning at 24 to 120 h postinfection and was continued for 5 days. Almost complete protection (87%) was observed when treatment with 1.5 mg/kg was begun at 72 h postinfection, and significant protection (73%) was still obtained when treatment with 5 mg/kg was initiated at 96 h. Virus titers in the liver, spleen, and kidney were reduced by about 4 log(10) units and about 2 log(10) units in mice infected with vaccinia virus and cowpox virus, respectively. These results indicate that 4'-thioIDU is a potent, nontoxic inhibitor of orthopoxvirus replication in cell culture and experimental animal infections and suggest that it may have potential for use in the treatment of orthopoxvirus infections in animals and humans.

  13. Synthesis and antimetabolic properties of 4,5-substituted pyrimidine 2'-deoxynucleosides and their 5'-monophosphates.

    PubMed

    Kulikowski, T; Bretner, M; Dzik, J M; Zieliński, Z; Cieśla, J; Rode, W; Vilpo, J A; Shugar, D

    1987-01-01

    Reaction of the reagent of Lawesson, 2,4-bis(p-methoxyphenyl)-1,3,4-dithiadiphosphatane-2,4-disulfide, with blocked uracil nucleosides in dioxane leads to quantitative thionation at C(4). With the bases, thionation occurs at C(4) and, with two equivalents of the reagent, at C(2) and C(4). Enzymatic phosphorylation of 4-thio-FdUrd gave the 5'-monophosphate, which was further converted with NH2OH to N4-hydroxy-FdCMP. Both nucleotides were examined as potential inhibitors of thymidylate synthase, and 4-thio-FdUrd for cytotoxic activities vs monkey and human leukemic cell lines.

  14. Periodate oxidation products of hydroxylysine in the synthesis of 5-substituted prolines.

    PubMed

    Wu, G Y; Seifter, S

    1985-05-15

    The amino acid hydroxylysine was subjected to oxidation by sodium metaperiodate under various conditions. It was found that in acid and high temperature, the initial oxidation product alpha-aminoglutaric gamma-semialdehyde was converted to glutamic acid with a yield of 60%. The use of alkaline conditions of oxidation favored the cyclization of alpha-aminoglutaric gamma-semialdehyde to form delta 1-pyrroline 5-carboxylic acid. Addition of NaCN to this intermediate generated new proline analogs, likely a mixture of cis- and trans-5-cyanoprolines, with a yield of 30%. Upon hydrolysis, the 5-cyanoprolines were converted to a probable mixture of cis- and trans-5-carboxyprolines. Infrared and high-resolution mass spectral data of the analogs and visual absorption spectra of the ninhydrin products were obtained to confirm the structures.

  15. 5-(hydroxymethyl)oxazoles: versatile scaffolds for combinatorial solid-phase synthesis of 5-substituted oxazoles.

    PubMed

    Grabowska, U; Rizzo, A; Farnell, K; Quibell, M

    2000-01-01

    A scheme combining the preparation of building blocks in solution followed by solid-phase combinatorial chemistry has been developed to side-chain diversify 5-(hydroxymethyl)oxazole scaffold (1) into aryl ethers, thioethers, sulfones, sulfonamides, and carboxamides. Protected heterocyclic scaffolds 2 were linked to the solid phase and N-terminal derivatized using active ester chemistry, providing chemset 4¿1-4,1-4¿. The free side-chain hydroxyl of 4 was smoothly converted to aryl ethers 6 under Mitsunobu conditions, with a broad range of substituted phenols. Alternatively, quantitative conversion of hydroxyl to bromide followed by displacement with alkyl and aryl thiols gave thioethers 8. Thioethers were optionally oxidized to sulfones 9. Bromide displacement by azide, followed by reduction to amine and acylation with a range of carboxylic acids and sulfonyl chlorides gave carboxamides 11 and sulfonamides 13, respectively. Crude purity at typically >90% was observed for each of the five modifications detailed. A series of 20 compounds, exemplifying each modification, was reprepared, purified, and fully characterized.

  16. Stable 5,5'-Substituted 2,2'-Bipyrroles: Building Blocks for Macrocyclic and Materials Chemistry.

    PubMed

    Anguera, Gonzalo; Kauffmann, Brice; Borrell, José I; Borrós, Salvador; Sánchez-García, David

    2017-07-07

    The preparation and characterization of a family of stable 2,2'-bipyrroles substituted at positions 5 and 5' with thienyl, phenyl, TMS-ethynyl, and vinyl groups is reported herein. The synthesis of these new bipyrroles comprises three steps: formation of the corresponding 5,5'-unsubstituted bipyrrole, bromination, and Stille or Suzuki coupling. The best results in the coupling are obtained using the Stille reaction under microwave irradiation. The new compounds have been fully characterized by UV-vis absorption, fluorescence, and IR spectroscopies and cyclic voltammetry. X-ray single-crystal analysis of four of the synthesized bipyrroles indicates a trans coplanar geometry of the pyrrole rings. Furthermore, the substituents at positions 5,5' remain coplanar to the central rings. This particular geometry extends the π-conjugation of the systems, which is in agreement with a red-shifting observed for the λmax of the substituted molecules compared to the unsubstituted bipyrrole. All of these new compounds display a moderate fluorescence. In contrast with unsubstituted bipyrroles, these bipyrroles are endowed with a high chemical and thermal stability and solubility in organic solvents.

  17. "Reverse fleximers": introduction of a series of 5-substituted carbocyclic uridine analogues.

    PubMed

    Sadler, Joshua M; Ojewoye, Olubukola; Seley-Radtke, Katherine L

    2008-01-01

    Nucleosides are ubiquitous in biological systems and as such, have been a focus of medicinal chemistry research in the search for new and potent therapeutic compounds. There are a number of modified nucleosides on the market, however increasing reports of resistance by mutation of either the enzyme binding site or the pathway that they are designed to interrupt are surfacing. As shown in recent reports, a candidate that can change conformation and still maintain recognition by the target enzyme would be highly desirable, and it is for this reason that flexible substrates have recently been sought as potential therapeutics. With this goal in mind, we have begun investigation into novel flexible scaffolds capable of overcoming viral resistance mechanisms resulting from binding site mutations.

  18. “Reverse Fleximers”: Introduction of a series of 5-substituted carbocyclic uridine analogues

    PubMed Central

    Sadler, Joshua M.; Ojewoye, Olubukola; Seley-Radtke, Katherine L.

    2009-01-01

    Nucleosides are ubiquitous in biological systems and as such, have been a focus of medicinal chemistry research in the search for new and potent therapeutic compounds. There are a number of modified nucleosides on the market, however increasing reports of resistance by mutation of either the enzyme binding site or the pathway that they are designed to interrupt are surfacing. As shown in recent reports, a candidate that can change conformation and still maintain recognition by the target enzyme would be highly desirable, and it is for this reason that flexible substrates have recently been sought as potential therapeutics. With this goal in mind, we have begun investigation into novel flexible scaffolds capable of overcoming viral resistance mechanisms resulting from binding site mutations. PMID:18776508

  19. NMR spectroscopy of the ligand binding core of ionotropic glutamate receptor 2 bound to 5-substituted willardiine partial agonists

    PubMed Central

    Fenwick, Michael K.; Oswald, Robert E.

    2008-01-01

    Glutamate receptors mediate neuronal intercommunication in the central nervous system by coupling extracellular neurotransmitter-receptor interactions to ion channel conductivity. To gain insight into structural and dynamical factors that underlie this coupling, solution NMR experiments were performed on the bi-lobed ligand-binding core of glutamate receptor 2 in complexes with a set of willardiine partial agonists. These agonists are valuable for studying structure-function relationships because their 5-position substituent size is correlated with ligand efficacy and extent of receptor desensitization whereas the substituent electronegativity is correlated with ligand potency. NMR results show that the protein backbone amide chemical shift deviations correlate mainly with efficacy and extent of desensitization. Pronounced deviations occur at specific residues in the ligand-binding site and in the two helical segments that join the lobes by a disulfide bond. Experiments detecting conformational exchange show that micro- to millisecond timescale motions also occur near the disulfide bond and vary largely with efficacy and extent of desensitization. These results thus identify regions displaying structural and dynamical dissimilarity arising from differences in ligand-protein interactions and lobe closure which may play a critical role in receptor response. Furthermore, measures of line broadening and conformational exchange for a portion of the ligand-binding site correlate with ligand EC50 data. These results do not have any correlate in the currently available crystal structures and thus provide a novel view of ligand-binding events that may be associated with agonist potency differences. PMID:18387631

  20. A convenient oxazole C-2 protecting group: the synthesis of 4- and 5-substituted oxazoles via metalation of 2-triisopropylsilyloxazoles.

    PubMed

    Miller, Ross A; Smith, Randi M; Marcune, Benjamin

    2005-10-28

    [reaction: see text] Metalation of oxazoles at the 4 and 5 position was achieved after regioselective C-2 silyl protection. Removal of the protecting group was then accomplished under mild conditions allowing for a straightforward preparation of C-5 monosubstituted and C-4,5 disubstituted oxazoles. The first practical C-2 protecting group of oxazoles has been demonstrated.

  1. Catalyst-free intramolecular oxidative cyclization of N-allylbenzamides: a new route to 2,5-substituted oxazoles.

    PubMed

    Zhou, Wei; Xie, Chen; Han, Jianlin; Pan, Yi

    2012-09-21

    A catalyst-free intramolecular oxidative cyclization reaction of N-allylbenzamides has been developed to prepare 2,5-disubstituted oxazoles with good yields. This reaction gives an efficient synthetic strategy to form an oxazole nucleus directly from easily accessible substrates under temperate conditions.

  2. Synthesis and biological evaluation of 5-substituted and 4,5-disubstituted-2-arylamino oxazole TRPV1 antagonists.

    PubMed

    Perner, Richard J; Koenig, John R; Didomenico, Stanley; Gomtsyan, Arthur; Schmidt, Robert G; Lee, Chih-Hung; Hsu, Margaret C; McDonald, Heath A; Gauvin, Donna M; Joshi, Shailen; Turner, Teresa M; Reilly, Regina M; Kym, Philip R; Kort, Michael E

    2010-07-01

    The synthesis and structure-activity relationships of a series of 5-monosubstituted and 4,5-disubstituted 2-arylaminooxazoles as novel antagonists of the transient receptor potential vanilloid 1 (TRPV1) receptor are described. The 7-hydroxy group of the tetrahydronaphthyl moiety on the 2-amino substituent of the oxazole ring was important for obtaining excellent in vitro potency at the human TRPV1 receptor, while a variety of alkyl and phenyl substituents at the 4- and 5-positions of the oxazole ring were well tolerated and yielded potent TRPV1 antagonists. Despite excellent in vitro potency, the 5-monosubstituted compounds suffered from poor pharmacokinetics. It was found that 4,5-disubstitution on the oxazole ring was critical to the improvement of the overall pharmacokinetic profile of these analogues, which led to the discovery of compound (R)-27, a novel TRPV1 antagonist with good oral activity in preclinical animal models of pain.

  3. Electron transport through 5-substituted pyrimidines in DNA: electron affinities of uracil and cytosine derivatives differently affect the apparent efficiencies.

    PubMed

    Ito, Takeo; Kurihara, Ryohsuke; Utsumi, Nihiro; Hamaguchi, Yuta; Tanabe, Kazuhito; Nishimoto, Sei-ichi

    2013-11-11

    We investigated excess electron transport (EET) in DNA containing cytosine derivatives. By arranging the derivatives according to their electron affinities, the apparent EET efficiency was successfully regulated. Unexpectedly, however, providing gradients of electron affinity by inserting 5-fluorocytosine did not always enhance EET.

  4. Two New Sandwich-Type Manganese {Mn5}-Substituted Polyoxotungstates: Syntheses, Crystal Structures, Electrochemistry, and Magnetic Properties.

    PubMed

    Gupta, Rakesh; Khan, Imran; Hussain, Firasat; Bossoh, A Martin; Mbomekallé, Israël M; de Oliveira, Pedro; Sadakane, Masahiro; Kato, Chisato; Ichihashi, Katsuya; Inoue, Katsuya; Nishihara, Sadafumi

    2017-08-07

    Herein we report two pentanuclear Mn(II)-substituted sandwich-type polyoxotungstate complexes, [{Mn(bpy)}2Na(H2O)2(MnCl)2{Mn(H2O)}(AsW9O33)2](9-) and [{Mn(bpy)}2Na(H2O)2(MnCl){Mn(H2O)}2(SbW9O33)2](8-) (bpy = 2,2'-bipyridine), whose structures have been obtained by single-crystal X-ray diffraction (SCXRD), complemented by results obtained from elemental analysis, electrospray ionization mass spectrometry, Fourier transform infrared spectroscopy, and thermogravimetric analysis. They consist of two [B-α-XW9O33](9-) subunits sandwiching a cyclic assembly of the hexagonal [{Mn(bpy)}2Na(H2O)2(MnCl)2{Mn(H2O)}](9+) and [{Mn(bpy)}2Na(H2O)2(MnCl){Mn(H2O)}2](10+) moieties, respectively, and represent the first pentanuclear Mn(II)-substituted sandwich-type polyoxometalates (POMs). Both compounds have been synthesized by reacting MnCl2·4H2O with trilacunary Na9[XW9O33]·27H2O (X = As(III) and Sb(III)) POM precursors in the presence of bpy in a 1 M aqueous sodium chloride solution under mild reaction conditions. SCXRD showed that the alternate arrangement of three five-coordinated Mn(II) ions and two six-coordinated Mn(II) ions with an internal Na cation formed a coplanar six-membered ring that was sandwiched between two [B-α-XW9O33](9-) (X = As(III) and Sb(III)) subunits. The results of temperature-dependent direct-current (dc) magnetic susceptibility data indicated ferromagnetic interactions between Mn ions in the cluster. Moreover, alternating-current magnetic susceptibility measurements with a dc-biased magnetic field showed the existence of a ferromagnetic order for both samples. Electrochemistry studies revealed the presence of redox processes assigned to the Mn centers. They are associated with the deposition of material on the working electrode surface, possibly MnxOy, as demonstrated by electrochemical quartz crystal microbalance experiments.

  5. Synthesis of 5-Substituted Derivatives of Isophthalic Acid as Non-Polymeric Amphiphilic Coating for Metal Oxide Nanoparticles

    PubMed Central

    Nilov, Denis; Kucheryavy, Pavel; Walker, Verina; Kidd, Clayton; Kolesnichenko, Vladimir L.; Goloverda, Galina Z.

    2014-01-01

    In the course of development of novel capping ligands with variable steric factor, which will be used as an organic coating for metal oxide nanoparticles, a base-catalyzed nucleophilic oxirane ring-opening addition reaction between dimethyl 5-hydroxyisophthalate and allyl glycidyl ether was studied. The allyl-terminated 1-1, 1-2 and 1-3 adducts and dihydroxylated derivative of the 1-1 adduct, 5-diglyceroxy isophthalic acid, were synthesized. The latter binds to the surface of 5 nm γ-Fe2O3 nanoparticles in reaction with their surfactant-free diethylene glycol colloids. PMID:25152545

  6. Synthesis, opioid receptor binding, and functional activity of 5'-substituted 17-cyclopropylmethylpyrido[2',3':6,7]morphinans.

    PubMed

    Ananthan, Subramaniam; Kezar, Hollis S; Saini, Surendra K; Khare, Naveen K; Davis, Peg; Dersch, Christina M; Porreca, Frank; Rothman, Richard B

    2003-02-10

    A series of naltrexone-derived pyridomorphinans possessing various substituents at the 5'-position on the pyridine ring were synthesized and evaluated for opioid receptor binding in rodent brain membranes and functional activity in smooth muscle preparations. While the introduction of aromatic 1-pyrrolyl group (6h) improved the delta affinity and delta antagonist potency of the parent compound (3), the introduction of guanidine group (6i) transformed it to a kappa selective ligand in opioid receptor binding and [35S]GTP-gamma-S functional assays.

  7. 4,5-Substituted 3-Isoxazolols with Insecticidal Activity Act as Competitive Antagonists of Housefly GABA Receptors.

    PubMed

    Liu, Genyan; Ozoe, Fumiyo; Furuta, Kenjiro; Ozoe, Yoshihisa

    2015-07-22

    The insect GABA receptor (GABAR), which is composed of five RDL subunits, represents an important target for insecticides. A series of 4,5-disubstituted 3-isoxazolols, including muscimol analogues, were synthesized and examined for their activities against four splice variants (ac, ad, bc, and bd) of housefly GABARs expressed in Xenopus oocytes. Muscimol was a more potent agonist than GABA in all four splice variants, whereas synthesized analogues did not exhibit agonism but rather antagonism in housefly GABARs. The introduction of bicyclic aromatic groups at the 4-position of muscimol and the simultaneous replacement of the aminomethyl group with a carbamoyl group at the 5-position to afford six 4-aryl-5-carbamoyl-3-isoxazolols resulted in compounds that exhibited significantly enhanced antagonism with IC50 values in the low micromolar range in the ac variant. The inhibition of GABA-induced currents by 100 μM analogues was approximately 1.5-4-fold greater in the ac and bc variants than in the ad and bd variants. 4-(3-Biphenylyl)-5-carbamoyl-3-isoxazolol displayed competitive antagonism, with IC50 values of 30, 34, 107, and 96 μM in the ac, bc, ad, and bd variants, respectively, and exhibited moderate insecticidal activity against houseflies, with an LD50 value of 5.6 nmol/fly. These findings suggest that these 3-isoxazolol analogues are novel lead compounds for the design and development of insecticides that target the orthosteric site of housefly GABARs.

  8. Development of 5-Substituted N-Methylmorphinan-6-ones as Potent Opioid Analgesics with Improved Side-Effect Profile.

    PubMed

    Schmidhammer, Helmut; Spetea, Mariana

    2012-01-01

    One of the most important functions of the opioid system is the control of pain. Among the three main opioid receptor classes (μ, δ, κ), the μ (MOR) is the main type targeted for pharmacotherapy of pain. Opioid analgesics such as morphine, oxycodone and fentanyl are agonists at the MOR and are the mainstay for the treatment of moderate-to-severe pain. However, adverse effects related to opioid use are severe and often lead to early discontinuation and inadequate analgesia. The development of more effective and safer medications for the management of pain still remains a major direction in pharmaceutical research. Chemical approaches towards the identification of novel MOR analgesics with reduced side effects include structural modifications of 14-alkoxy-N-methylmorphinan-6-ones in key positions that are important for binding, selectivity, potency, and efficacy at opioid receptors. This paper describes a representative strategy to improve the therapeutic usefulness of opioid analgesics from the morphinan class of drugs by targeting position 5. The focus is on chemical and biological studies and structure-activity relationships of this series of ligands. We report on 14-alkoxymorphinan-6-ones having a methyl and benzyl group at position 5 as strong opioid antinociceptive agents with reduced propensity to cause undesired effects compared to morphine although interacting selectively with MORs.

  9. Unusual behavior in the reactivity of 5-substituted-1H-tetrazoles in a resistively heated microreactor

    PubMed Central

    Gutmann, Bernhard; Glasnov, Toma N; Razzaq, Tahseen; Goessler, Walter; Roberge, Dominique M

    2011-01-01

    Summary The decomposition of 5-benzhydryl-1H-tetrazole in an N-methyl-2-pyrrolidone/acetic acid/water mixture was investigated under a variety of high-temperature reaction conditions. Employing a sealed Pyrex glass vial and batch microwave conditions at 240 °C, the tetrazole is comparatively stable and complete decomposition to diphenylmethane requires more than 8 h. Similar kinetic data were obtained in conductively heated flow devices with either stainless steel or Hastelloy coils in the same temperature region. In contrast, in a flow instrument that utilizes direct electric resistance heating of the reactor coil, tetrazole decomposition was dramatically accelerated with rate constants increased by two orders of magnitude. When 5-benzhydryl-1H-tetrazole was exposed to 220 °C in this type of flow reactor, decomposition to diphenylmethane was complete within 10 min. The mechanism and kinetic parameters of tetrazole decomposition under a variety of reaction conditions were investigated. A number of possible explanations for these highly unusual rate accelerations are presented. In addition, general aspects of reactor degradation, corrosion and contamination effects of importance to continuous flow chemistry are discussed. PMID:21647324

  10. Development of 5-Substituted N-Methylmorphinan-6-ones as Potent Opioid Analgesics with Improved Side-Effect Profile

    PubMed Central

    Schmidhammer, Helmut; Spetea, Mariana

    2012-01-01

    One of the most important functions of the opioid system is the control of pain. Among the three main opioid receptor classes (μ, δ, κ), the μ (MOR) is the main type targeted for pharmacotherapy of pain. Opioid analgesics such as morphine, oxycodone and fentanyl are agonists at the MOR and are the mainstay for the treatment of moderate-to-severe pain. However, adverse effects related to opioid use are severe and often lead to early discontinuation and inadequate analgesia. The development of more effective and safer medications for the management of pain still remains a major direction in pharmaceutical research. Chemical approaches towards the identification of novel MOR analgesics with reduced side effects include structural modifications of 14-alkoxy-N-methylmorphinan-6-ones in key positions that are important for binding, selectivity, potency, and efficacy at opioid receptors. This paper describes a representative strategy to improve the therapeutic usefulness of opioid analgesics from the morphinan class of drugs by targeting position 5. The focus is on chemical and biological studies and structure-activity relationships of this series of ligands. We report on 14-alkoxymorphinan-6-ones having a methyl and benzyl group at position 5 as strong opioid antinociceptive agents with reduced propensity to cause undesired effects compared to morphine although interacting selectively with MORs. PMID:25954525

  11. Singlet-triplet energy differences in divalent five membered cyclic conjugated Arduengo-type carbenes XC2HN2M (M = C, Si, Ge, Sn, and Pb; X = F, Cl, Br, and I)

    NASA Astrophysics Data System (ADS)

    Vessally, Esmail; Dehbandi, Behnam; Ahmadi, Elaheh

    2016-09-01

    Singlet-triplet energy differences in Arduengo-type carbenes XC2HN2C compared and contrasted with their sila, germa, stana and plumba analogues; at B3LYP/6-311++G** level of theory. Free Gibbs energy differences between triplet (t) and singlet (s) states (Δ G(t-s)) change in the following order: plumbylenes > stannylenes > germylenes > silylenes > carbenes. The singlet states in XC2HN2C are generally more stable when the electron withdrawing groups such as-F was used at β-position. However, the singlet states in XC2N2HM (M = Si, Ge, Sn, and Pb) are generally more stable when the withdrawing groups such as-F was placed. The puckering energy is investigated for each the singlet and triplet states. The DFT calculations found the linear correlation to size of the group 14 divalent element (M), the ∠N-M-N angle, and the Δ(LUMO-HOMO) of XC2HN2M.

  12. Design, synthesis, evaluation and molecular modelling studies of some novel 5,6-diphenyl-1,2,4-triazin-3(2H)-ones bearing five-member heterocyclic moieties as potential COX-2 inhibitors: A hybrid pharmacophore approach.

    PubMed

    Banerjee, Anupam G; Das, Nirupam; Shengule, Sushant A; Sharma, Piyoosh A; Srivastava, Radhey Shyam; Shrivastava, Sushant Kumar

    2016-12-01

    A series of novel hybrids comprising of 1,3,4-oxadiazole/thiadiazole and 1,2,4-triazole tethered to 5,6-diphenyl-1,2,4-triazin-3(2H)-one were designed, synthesised and evaluated as COX-2 inhibitors for the treatment of inflammation. The synthesised hybrids were characterised using FT-IR, 1H NMR, 13C NMR, elemental (C,H,N) analyses and assessed for their anti-inflammatory potential by in vitro albumin denaturation assay. Compounds exhibiting activity comparable to indomethacin and celecoxib were further evaluated for in vivo anti-inflammatory activity. Oral administration of promising compounds 3c-3e and 4c-4e did not evoke significant gastric, hepatic and renal toxicity in rats. These potential compounds exhibited reduced malondialdehyde (MDA) content on the gastric mucosa suggesting their protective effects by inhibition of lipid peroxidation. Based on the outcome of in vitro COX assay, compounds 3c-3e and 4c-4e (IC50 0.60-1.11μM) elicited an interesting profile as competitive selective COX-2 inhibitors. Further, selected compounds 3e and 4c were found devoid of cardiotoxicity post evaluation on myocardial infarcted rats. The in silico binding mode of the potential compounds into the COX-2 active site through docking and molecular dynamics exemplified their consensual interaction and subsequent COX-2 inhibition with significant implications for structure-based drug design.

  13. Characterization and electronic structures of five members of the electron transfer series [Re(benzene-1,2-dithiolato)3](z) (z = 1+, 0, 1-, 2-, 3-): a spectroscopic and density functional theoretical study.

    PubMed

    Sproules, Stephen; Benedito, Flávio Luiz; Bill, Eckhard; Weyhermüller, Thomas; DeBeer George, Serena; Wieghardt, Karl

    2009-12-07

    The reaction of ReCl(5) with 3 equiv of a benzene-1,2-dithiolate derivative in CH(3)CN produced, after the addition of [C(8)H(16)N]Br ([C(8)H(16)N](+) is 5-azonia-spiro[4,4]nonane), brownish-green crystals of [C(8)H(16)N][Re(tms)(3)] (1c) and [C(8)H(16)N][Re(Cl(2)-bdt)(3)] (2c), where (tms)(2-) represents 3,6-bis(trimethylsilyl)benzene-1,2-dithiolate and (Cl(2)-bdt)(2-) is 3,6-dichlorobenzene-1,2-dithiolate. Chemical reduction of [Re(bdt)(3)] (3b) with n-butyllithium in the presence of PPh(4)Br yielded [PPh(4)][Re(bdt)(3)] (3c), where (bdt)(2-) is benzene-1,2-dithiolate. The three monoanionic complexes possess a diamagnetic ground state (Re(V), d(2), S = 0). The crystal structures of 1c x 2 CH(3)CN and 2c x C(3)H(6)O have been determined by X-ray crystallography. The electrochemistry establishes that the complexes are members of electron transfer series involving a monocation [Re(V)(L(*))(2)(L)](+) (S = 0(?)), a neutral [Re(V)(L(*))(L)(2)](0) (S = 1/2), a monoanion [Re(V)(L)(3)](1-) (S = 0), a dianion [Re(IV)(L)(3)](2-) (S = 1/2), and a trianion [Re(III)(L)(3)](3-) (S = 1(?)). The unique X-band EPR spectrum of the neutral species clearly describes a diamagnetic Re(V) d(2) central ion with the unpaired electron located in a purely ligand-centered molecular orbital, whereas it is metal-centered in the dianionic form: a Re(IV) d(3) ion with three dithiolate(2-) ligands. S K-edge and Re L-edge X-ray absorption spectroscopy confirms these assignments and furthermore shows that the monoanion has a Re(V) central ion with three dianionic ligands. The geometrical and electronic structures of all members of the electron transfer series have been calculated by density functional theoretical methods, and the S K-pre-edge spectra have been simulated and assigned using a time-dependent DFT protocol.

  14. Design synthesis and structure–activity relationship of 5-substituted (tetrahydronaphthalen-2yl)methyl with N-phenyl-N-(piperidin-2-yl) propionamide derivatives as opioid ligands

    PubMed Central

    Deekonda, Srinivas; Rankin, David; Davis, Peg; Lai, Josephine; Vanderah, Todd. W.; Porecca, Frank; Hruby, Victor J.

    2016-01-01

    Here, we report the design, synthesis and structure activity relationship of novel small molecule opioid ligands based on 5-amino substituted (tetrahydronaphthalen-2-yl)methyl moiety with N-phenyl-N-(piperidin-2-yl)propionamide derivatives. We synthesized various molecules including amino, amide and hydroxy substitution on the 5th position of the (tetrahydronaphthalen-2-yl)methyl moiety. In our further designs we replaced the (tetrahydronaphthalen-2-yl)methyl moiety with benzyl and phenethyl moiety. These N-phenyl-N-(piperidin-2-yl)propionamide analogues showed moderate to good binding affinities (850–4 nM) and were selective towards the μ opioid receptor over the δ opioid receptors. From the structure activity relationship studies, we found that a hydroxyl substitution at the 5th position of (tetrahydronapthalen-2yl)methyl group, ligands 19 and 20, showed excellent binding affinities 4 and 5 nM, respectively, and 1000 fold selectivity towards the μ opioid relative to the delta opioid receptor. The ligand 19 showed potent agonist activities 75 ± 21 nM, and 190 ± 42 nM in the GPI and MVD assays. Surprisingly the fluoro analogue 20 showed good agonist activities in MVD assays 170 ± 42 nM, in contrast to its binding affinity results. PMID:26712115

  15. Coordination chemistry of N,N,N',N'-tetrakis(3,5-substituted benzyl-2-oxide)-2,2'-(ethylenedioxy)diethanamine modified Group 4 metal alkoxides.

    PubMed

    Boyle, Timothy J; Yonemoto, Daniel T; Steele, Leigh Anna; Farrell, Joshua; Renehan, Peter; Huhta, Taylor

    2012-11-05

    The coordination behavior of a set of (ethylenedioxy)diethanamine-based tetraphenol ligands with a series of Group 4 metal alkoxides ([M(OR)(4)]) was determined. The ligands were synthesized from a modified Mannich reaction and fully characterized as N,N,N',N'-tetrakis(3,5-tert-butyl-benzyl-2-hydroxy)-2,2'-(ethylenedioxy)diethanamine, termed H(4)-OEA-DBP(4) (1), and N,N,N',N'-tetrakis(3,5-chloro-benzyl-2-hydroxy)-2,2'-(ethylenedioxy)diethanamine, termed H(4)-OEA-DCP(4) (2). The reaction of 1 with a set of [M(OR)(4)] [M = Ti, Zr, or Hf; OR = iso-propoxide (OPr(i)), neo-pentoxide (ONep), or tert-butoxide (OBu(t))] precursors led to the isolation of [(OPr(i))(2)Ti](2)(μ-OEA-DBP(4)) (3), [(ONep)(2)Ti](2)(μ-OEA-DBP(4)) (4), and [(OBu(t))(2)M](2)(μ-OEA-DBP(4)) where M = Ti (5), Zr (6), or Hf (7). In addition, the [(ONep)(2)Ti](2)(μ-OEA-DCP(4)) (4a) derivative was isolated from the reaction of 2 and [Ti(ONep)(4)], demonstrating the similarity of coordination behavior between the two OEA-R(4) ligands. For 3-7, the metal center adopts a slightly distorted octahedral geometry by binding the two O atoms of the phenoxide moiety, as well as one N and one O atom from the OEA moieties, while retaining two of the original OR ligands. Solution NMR demonstrates inequivalent protons for the majority of the bound OEA ligands, which argues for retention of structure in solution. The synthesis and characterization of these compounds are presented in detail.

  16. Synthesis, physicochemical properties, and hydrogen bonding of 4(5)-substituted 1-H-imidazole-2-carboxamide, a potential universal reader for DNA sequencing by recognition tunneling.

    PubMed

    Liang, Feng; Li, Shengqing; Lindsay, Stuart; Zhang, Peiming

    2012-05-07

    We have developed a chemical reagent that recognizes all naturally occurring DNA bases, a so called universal reader, for DNA sequencing by recognition tunneling in nanopores.1 The primary requirements for this type of molecules are the ability to form non-covalent complexes with individual DNA bases and to generate recognizable electronic signatures under an electrical bias. 1-H-imidazole-2-carboxamide was designed as such a recognition moiety to interact with the DNA bases through hydrogen bonding. In the present study, we first furnished a synthetic route to 1-H-imidazole-2-carboxamide containing a short ω-functionalized alkyl chain at its 4(5) position for its attachment to metal and carbon electrodes. The acid dissociation constants of the imidazole-2-carboxamide were then determined by UV spectroscopy. The data show that the 1-H-imidazole-2-carboxamide exists in a neutral form between pH 6-10. Density functional theory (DFT) and NMR studies indicate that the imidazole ring exists in prototropic tautomers. We propose an intramolecular mechanism for tautomerization of 1-H-imidazole-2-carboxamide. In addition, the imidazole-2-carboxamide can self-associate to form hydrogen bonded dimers. NMR titration found that naturally occurring nucleosides interacted with 1-H-imidazole-2-carboxamide through hydrogen bonding in a tendency of dG>dC≫dT>dA. These studies are indispensable to assisting us in understanding the molecular recognition that takes place in the nanopore where routinely used analytical tools such as NMR and FTIR cannot be conveniently applied. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Oxidative phenylamination of 5-substituted 1-hydroxynaphthalenes to N-phenyl-1,4-naphthoquinone monoimines by air and light “on water”

    PubMed Central

    Meléndez, Juan; Estela, Cynthia; Ríos, David; Espinoza, Luis; Brito, Iván; Valderrama, Jaime A

    2014-01-01

    Summary A number of N-phenyl-1,4-naphthoquinone monoimines 6–10 were prepared by on-water oxidative phenylamination of 1,5-dihydroxynaphthalene (1) and 5-acetylamino-1-hydroxynaphthalene (5) with oxygen-substituted phenylamines under aerobic conditions and either solar or green LED radiation, in the presence of rose bengal as singlet oxygen sensitizer. As compared to the conventional oxidative phenylamination procedures, this novel synthetic method offers the advantage of aerobic conditions “on water” instead of hazardous oxidant reagents currently employed in aqueous alcoholic media. PMID:25383115

  18. Alternating 2,6-/3,5-substituted pyridine-acetylene macrocycles: π-stacking self-assemblies enhanced by intermolecular dipole-dipole interaction.

    PubMed

    Abe, Hajime; Ohtani, Kohei; Suzuki, Daiki; Chida, Yusuke; Shimada, Yuta; Matsumoto, Shinya; Inouye, Masahiko

    2014-02-07

    Macrocyclic compounds consisting of three 2,6-pyridylene and three 3,5-pyridylene units linked by acetylene bonds were synthesized by a Sonogashira reaction. The X-ray structures showed π-stacked pairs of two macrocycles, in which a 2,6-pyridylene unit of the one molecule overlaps a 3,5-pyridylene of the other molecule because of dipole-dipole interaction. Atomic force microscope (AFM) measurements revealed fibril structures indicating the stacking of the rigid planar macrocycles. Hydrogen-bonding ability of the macrocyclic inside was demonstrated by the addition of octyl β-D-glucopyranoside.

  19. Computational chemistry applied to vibrational spectroscopy: A tool for characterization of nucleic acid bases and some of their 5-substituted derivatives

    NASA Astrophysics Data System (ADS)

    Palafox, M. Alcolea

    2017-08-01

    Computational chemistry can be applied to vibrational spectroscopy in different ways, such as for a better characterization and assignment of all the bands of the experimental spectra, as a tool in the identification of the tautomers present in the gas phase and in the solid state through their spectra and for the simulation of the solid and liquid phase of a compound and the consequent simulation and interpretation of their spectra. In the present study, as an example of the applicability of computational chemistry, the structure and spectra of cytosine and uracil nucleic acid bases and two cytosine derivatives are shown. The FTIR and Raman spectra were analysed with the support of ab initio (Hartree-Fock (HF), MP2) and density functional theory (DFT) (B3LYP, PBE, B-P, etc.) calculations using several basis sets and several scaling equations. The calculations predict an easier tautomerization of cytosine than uracil molecule, but the tautomerization is hindered in the 5-bromocytosine molecule. Thus, in the solid state, this molecule only exists in the amino-oxo tautomeric form.

  20. Synthesis of novel 1H-1,2,3-triazole tethered C-5 substituted uracil-isatin conjugates and their cytotoxic evaluation.

    PubMed

    Kumar, Kewal; Sagar, Sunil; Esau, Luke; Kaur, Mandeep; Kumar, Vipan

    2012-12-01

    The present manuscript describes the synthesis of uracil-isatin hybrids via azide-alkyne cycloadditions and their cytotoxic evaluation against three human cancer cell lines viz. HeLa (cervix), MCF-7 (breast) and DU145 (prostate) using MTT assay. The evaluation studies revealed the dependence of cytotoxicity on C-5 substituents of both uracil and isatin as well as the alkyl chain length with compounds 6g and 6k showing IC(50) values 18.21 and 13.90 μM respectively against DU145 cell lines. Most of the synthesized conjugates exhibited considerable selectivity against MCF-7 and DU145 cell lines. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  1. Synthesis, Biological Evaluation, and Molecular Modeling of 3,5-Substituted-N1-phenyl-N4, N4-di-n-butylsulfanilamides as Antikinetoplastid Antimicrotubule Agents

    PubMed Central

    George, Tesmol G.; Endeshaw, Molla M.; Morgan, Rachel E.; Mahasenan, Kiran V.; Delfín, Dawn A.; Mukherjee, Mitali S.; Yakovich, Adam J.; Fotie, Jean; Li, Chenglong; Werbovetz, Karl A.

    2007-01-01

    Dinitroanilines are of interest as antiprotozoal lead compounds because of their selective activity against the tubulin of these organisms, but concern has been raised due the potentially mutagenic nitro groups. Analogues of N1-phenyl-3,5-dinitro-N4,N4-di-n-butylsulfanilamide (GB-II-150, compound 2b), a selective antimitotic agent against African trypanosomes and Leishmania, have been prepared where the nitro groups are replaced with amino, chloro, cyano, carboxylate, methyl ester, amide, and methyl ketone moieties. Dicyano compound 5 displays IC50 values that are comparable to 2b against purified leishmanial tubulin assembly (6.6 vs. 7.4 μM), Trypanosoma brucei brucei growth in vitro (0.26 vs. 0.18 μM), L. donovani axenic amastigote growth in vitro (4.4 vs. 2.3 μM), and in vitro toxicity against Vero cells (16 vs. 9.7 μM). Computational studies provide a rationale for the antiparasitic order of activity of these analogues and further insight into the role of the substituents at the 3 and 5 positions of the sulfanilamide ring. PMID:17618122

  2. Copper(II) complexes of N-(2-{[(2E)-2-(2-Hydroxy-(5-substituted)-benzylidene)-hydrazino]carbonyl}phenyl)benzamide ligands and heterocyclic coligands.

    PubMed

    Chavan, S S; Sawant, V A; Jadhav, A N

    2014-01-03

    Some copper(II) complexes of the type [Cu(L1-3)(phen]·CH2Cl2 (1a-3a) and [Cu(L1-3) (bipy)]·CH2Cl2 (1b-3b) (where L1=N-(2-{[(2E)-2-(2-Hydroxy-benzylidene)-hydrazino]carbonyl}phenyl)benzamide, L2=N-(2-{[(2E)-2-(2-Hydroxy-(5-bromo)-benzylidene)-hydrazino]carbonyl}phenyl)benzamide, L3=N-(2-{[(2E)-2-(2-Hydroxy-(5-methoxy)-benzylidene)-hydrazino]carbonyl}phenyl)benzamide; phen=1,10-phenanthroline, bipy=2,2'-bipyridine) have been prepared and characterized on the basis of elemental analyses, IR, UV-Vis and EPR spectral studies. IR spectra indicate that the ligand L1-3 exists in the keto form in the solid state, while at the time of complexation, it tautomerises into enol form. The single crystal X-ray diffraction study of the representative complex [Cu(L1) (phen)]·CH2Cl2 (1a) reveals the distorted square pyramidal geometry around copper(II). Crystal data of (1a): space group=P21/n, a=11.5691(16) Å, b=11.0885(15) Å, c=24.890(4) Å, V=3166.2(8) Å(3), Z=4. The electrochemical behavior of all the complexes indicate that the phen complexes appears at more positive potential as compared to those for bipy complexes, as a consequence of its stronger π acidic character. All the complexes exhibit blue-green emission as a result of the fluorescence from the intra-ligand (π→π(*)) emission excited state.

  3. Structure-Activity Relationships in a Novel Series of 7-Substituted-Aryl Quinolines and 5-Substituted-Aryl Benzothiazoles at the Metabotropic Glutamate Receptor Subtype 5

    PubMed Central

    Zhang, Peng; Zou, Mu-Fa; Rodriguez, Alice L.; Conn, P. Jeffrey; Newman, Amy Hauck

    2010-01-01

    The metabotropic glutamate receptor subtype 5 (mGluR5) has been implicated in numerous neuropsychiatric disorders including addiction. We have discovered that the rigid diaryl alkyne template, derived from the potent and selective noncompetitive mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP), can serve to guide the design of novel quinoline analogues and pharmacophore optimization has resulted in potent mGluR5 noncompetitive antagonists (EC50 range 60–100 nM) in the quinoline series. PMID:20382541

  4. Base-pairing energies of proton-bound homodimers determined by guided ion beam tandem mass spectrometry: application to cytosine and 5-substituted cytosines.

    PubMed

    Yang, Bo; Wu, R R; Rodgers, M T

    2013-11-19

    Base-pairing interactions in proton-bound dimers of cytosine (C(+)·C) are the major forces responsible for stabilization of DNA i-motif conformations. Permethylation of cytosine in extended (CCG)·(CGG)n trinucleotide repeats has been shown to cause fragile-X syndrome, the most widespread inherited cause of mental retardation in humans. Oligonucleotides containing 5-bromo- or 5-fluorocytosine can bind to proteins that selectively bind methylated DNA, suggesting that halogenated cytosine damage products can potentially mimic methylation signals. However, the influence of methylation or halogenation on the base-pairing energies (BPEs) of proton-bound dimers of cytosine and their impact on the stability of DNA i-motif conformations is presently unknown. To address this, proton-bound homodimers of cytosine and 5-methyl-, 5-fluoro-, 5-bromo-, and 5-iodocytosine are investigated in detail both experimentally and theoretically. The BPEs of proton-bound homodimers of cytosine and the modified cytosines are measured by threshold collision-induced dissociation (TCID) techniques. 5-Methylation of cytosine is found to increase the BPE and would therefore tend to stabilize DNA i-motif conformations. In contrast, 5-halogenation lowers the BPE. However, the BPEs of the proton-bound 5-halocytosine homodimers examined here still significantly exceed that of Watson-Crick G·C base pairs, such that DNA i-motif conformations should be preserved in the presence of these modifications. Excellent agreement between TCID measured and B3LYP calculated BPEs is found, suggesting that B3LYP calculations can be used to provide reliable energetic predictions for related systems.

  5. Ir-catalyzed preparation of SF5-substituted potassium aryl trifluoroborates via C-H borylation and their application in the Suzuki-Miyaura reaction.

    PubMed

    Joliton, Adrien; Carreira, Erick M

    2013-10-18

    The preparation of new pentafluorosulfanyl-substituted potassium aryltrifluoroborates via Ir-catalyzed C-H borylation is reported. The utility of these novel building blocks was demonstrated in the Suzuki-Miyaura cross-coupling reaction, giving access to 3,5-disubstituted pentafluorosulfanylbenzenes.

  6. Arylazoindazole Photoswitches: Facile Synthesis and Functionalization via SNAr Substitution

    PubMed Central

    2017-01-01

    A straightforward synthetic route to arylazoindazoles via nucleophilic aromatic substitution is presented. Upon deprotonation of the NH group, a C6F5-substituted formazan undergoes facile cyclization as a result of intermolecular nucleophilic substitution (SNAr). This new class of azo photoswitches containing an indazole five-membered heterocycle shows photochemical isomerization with high fatigue resistance. In addition, the Z-isomers have long thermal half-lives in the dark of up to several days at room temperature. The fluorinated indazole group offers a handle for further functionalization and tuning of its properties, as it is shown to be susceptible to a subsequent, highly selective nucleophilic displacement reaction. PMID:28218846

  7. Novel pyridyl ring C5 substituted analogues of epibatidine and 3-(1-methyl-2(S)-pyrrolidinylmethoxy)pyridine (A-84543) as highly selective agents for neuronal nicotinic acetylcholine receptors containing beta2 subunits.

    PubMed

    Wei, Zhi-Liang; Xiao, Yingxian; Yuan, Hongbin; Baydyuk, Maryna; Petukhov, Pavel A; Musachio, John L; Kellar, Kenneth J; Kozikowski, Alan P

    2005-03-24

    Introduction of a hydrophobic or hydrogen-bonding alkynyl group into the C5 position of the pyridyl ring of epibatidine and A-84543 significantly increased the selectivity for neuronal nicotinic acetylcholine receptors (nAChRs) containing beta2 subunits over nAChRs containing beta4 subunits (K(i) ratio up to 92000-fold). Our data indicate that the extracellular domains of the nAChRs are sufficiently different to allow for the design of novel ligands with high affinity and selectivity for the nAChR subtypes.

  8. Synthesis, characterization, evaluation and molecular dynamics studies of 5, 6-diphenyl-1,2,4-triazin-3(2H)-one derivatives bearing 5-substituted 1,3,4-oxadiazole as potential anti-inflammatory and analgesic agents.

    PubMed

    Banerjee, Anupam G; Das, Nirupam; Shengule, Sushant A; Srivastava, Radhey Shyam; Shrivastava, Sushant Kumar

    2015-08-28

    A series of triazin-3(2H)-one derivatives bearing 1,3,4-oxadiazole (4a-4o) were synthesized, characterized and evaluated for anti-inflammatory and analgesic activities. Preliminary in vitro anti-inflammatory activity was assessed using an albumin denaturation assay. The promising compounds were further evaluated in acute, sub-chronic and chronic animal models of inflammation. Derivatives 4d, 4e, 4g, 4j and 4l exhibited significant anti-inflammatory activity with reduced ulcerogenic, hepatotoxic and renotoxic liabilities compared to standard indomethacin. These potential derivatives were also evaluated for in vivo analgesic activity using a writhing model and the formalin-induced paw licking response in mice. Compounds 4d, 4e and 4g exhibited comparable analgesic activity, whereas 4j and 4l yielded moderate effects. The specificity of compounds 4d, 4e, 4g, 4j, and 4l to inhibit (cyclooxygenase-1) COX-1 and (cyclooxygenase-2) COX-2 isozymes and their kinetics were also determined via an in vitro COX inhibition assay. In silico docking studies were performed using a molecular dynamics simulation of the most active compound 4d (COX-2 IC50: 3.07 μM) at the COX-2 active site. The outcome of this exercise helped to verify the consensual interaction of these compounds with the enzyme.

  9. Influence of C-5 substituted cytosine and related nucleoside analogs on the formation of benzo[a]pyrene diol epoxide-dG adducts at CG base pairs of DNA.

    PubMed

    Guza, Rebecca; Kotandeniya, Delshanee; Murphy, Kristopher; Dissanayake, Thakshila; Lin, Chen; Giambasu, George Madalin; Lad, Rahul R; Wojciechowski, Filip; Amin, Shantu; Sturla, Shana J; Hudson, Robert H E; York, Darrin M; Jankowiak, Ryszard; Jones, Roger; Tretyakova, Natalia Y

    2011-05-01

    Endogenous 5-methylcytosine ((Me)C) residues are found at all CG dinucleotides of the p53 tumor suppressor gene, including the mutational 'hotspots' for smoking induced lung cancer. (Me)C enhances the reactivity of its base paired guanine towards carcinogenic diolepoxide metabolites of polycyclic aromatic hydrocarbons (PAH) present in cigarette smoke. In the present study, the structural basis for these effects was investigated using a series of unnatural nucleoside analogs and a representative PAH diolepoxide, benzo[a]pyrene diolepoxide (BPDE). Synthetic DNA duplexes derived from a frequently mutated region of the p53 gene (5'-CCCGGCACCC GC[(15)N(3),(13)C(1)-G]TCCGCG-3', + strand) were prepared containing [(15)N(3), (13)C(1)]-guanine opposite unsubstituted cytosine, (Me)C, abasic site, or unnatural nucleobase analogs. Following BPDE treatment and hydrolysis of the modified DNA to 2'-deoxynucleosides, N(2)-BPDE-dG adducts formed at the [(15)N(3), (13)C(1)]-labeled guanine and elsewhere in the sequence were quantified by mass spectrometry. We found that C-5 alkylcytosines and related structural analogs specifically enhance the reactivity of the base paired guanine towards BPDE and modify the diastereomeric composition of N(2)-BPDE-dG adducts. Fluorescence and molecular docking studies revealed that 5-alkylcytosines and unnatural nucleobase analogs with extended aromatic systems facilitate the formation of intercalative BPDE-DNA complexes, placing BPDE in a favorable orientation for nucleophilic attack by the N(2) position of guanine.

  10. Design synthesis and structure-activity relationship of 5-substituted (tetrahydronaphthalen-2yl)methyl with N-phenyl-N-(piperidin-2-yl)propionamide derivatives as opioid ligands.

    PubMed

    Deekonda, Srinivas; Rankin, David; Davis, Peg; Lai, Josephine; Vanderah, Todd W; Porecca, Frank; Hruby, Victor J

    2016-01-15

    Here, we report the design, synthesis and structure activity relationship of novel small molecule opioid ligands based on 5-amino substituted (tetrahydronaphthalen-2-yl)methyl moiety with N-phenyl-N-(piperidin-2-yl)propionamide derivatives. We synthesized various molecules including amino, amide and hydroxy substitution on the 5th position of the (tetrahydronaphthalen-2-yl)methyl moiety. In our further designs we replaced the (tetrahydronaphthalen-2-yl)methyl moiety with benzyl and phenethyl moiety. These N-phenyl-N-(piperidin-2-yl)propionamide analogues showed moderate to good binding affinities (850-4 nM) and were selective towards the μ opioid receptor over the δ opioid receptors. From the structure activity relationship studies, we found that a hydroxyl substitution at the 5th position of (tetrahydronapthalen-2yl)methyl group, ligands 19 and 20, showed excellent binding affinities 4 and 5 nM, respectively, and 1000 fold selectivity towards the μ opioid relative to the delta opioid receptor. The ligand 19 showed potent agonist activities 75±21 nM, and 190±42 nM in the GPI and MVD assays. Surprisingly the fluoro analogue 20 showed good agonist activities in MVD assays 170±42 nM, in contrast to its binding affinity results.

  11. Stereocontrolled Cyanohydrin Ether Synthesis through Chiral Brønsted Acid-Mediated Vinyl Ether Hydrocyanation

    PubMed Central

    Lu, Chunliang; Su, Xiaoge; Floreancig, Paul E.

    2013-01-01

    Vinyl ethers can be protonated to generate oxocarbenium ions that react with Me3SiCN to form cyanohydrin alkyl ethers. Reactions that form racemic products proceed efficiently upon converting the vinyl ether to an α-chloro ether prior to cyanide addition in a pathway that proceeds through Brønsted acid-mediated chloride ionization. Enantiomerically enriched products can be accessed by directly protonating the vinyl ether with a chiral Brønsted acid to form a chiral ion pair. Me3SiCN acts as the nucleophile and PhOH serves as a stoichiometric proton source in a rare example of an asymmetric bimolecular nucleophilic addition reaction into an oxocarbenium ion. Computational studies provide a model for the interaction between the catalyst and the oxocarbenium ion. PMID:23968162

  12. Synthesis of Bridged Inside-Outside Bicyclic Ethers through Oxidative Transannular Cyclization Reactions

    PubMed Central

    Han, Xun

    2012-01-01

    The classical geometry of the 6-endo transition state for nucleophilic additions into oxocarbenium ions can be perturbed by incorporating the reactive groups into medium sized rings, leading to the formation of 2,6-trans-dialkyl tetrahydropyrans. The bicyclic products exhibit inside-outside stereoisomerism, as seen in numerous macrolide natural products. PMID:22783950

  13. The effect of ZnO ↔ Ta{sub 2}O{sub 5} substitution on the structural and thermal properties of SiO{sub 2}-ZnO-SrO-CaO-P{sub 2}O{sub 5} glasses

    SciTech Connect

    Alhalawani, Adel M.F.; Towler, Mark R.

    2016-04-15

    A series of glasses based on the system 48SiO{sub 2}-(36-X) ZnO-6CaO-8SrO-2P{sub 2}O{sub 5}-XTa{sub 2}O{sub 5} with X varying from 0 mol% (Ta0) to 8 mol% (Ta4) were fabricated. The structural features as a function of Ta{sub 2}O{sub 5} content were investigated by network connectivity (NC) calculations, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). The thermal properties of the glasses were obtained by performing simultaneous thermal analysis (STA). XRD showed that all compositions were predominantly amorphous, however the incorporation of tantalum pentoxide (Ta{sub 2}O{sub 5}) resulted in a small degree of crystallinity within the sample. Replacing ZnO with Ta{sub 2}O{sub 5} increases the glass transition, crystallization and melting temperatures. Further, Ta{sub 2}O{sub 5} incorporation results in higher thermal stability suggesting a greater glass forming tendency and the insertion of Ta in the glass network. XPS and FTIR spectroscopy revealed that Ta behaves as a glass former and that Zn has an intermediary role in the vitreous network. - Highlights: • ZnO substitution for Ta{sub 2}O{sub 5} in the glass system SiO{sub 2}-ZnO-CaO-SrO-P{sub 2}O{sub 5} is presented. • ZnO substitution results in greater glass forming tendency. • Ta{sub 2}O{sub 5} addition results in the formation of Si−O−Ta and Ta−O−Ta linkages. • Ta{sub 2}O{sub 5} addition increases the glass thermal stability. • ZnO behaves as an intermediate in this glass system.

  14. Coordination polymers of 5-substituted isophthalic acid† †Electronic supplementary information (ESI) available. CCDC 1417516–1417520 contain the supplementary crystallographic data for this paper. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5ce02091c Click here for additional data file. Click here for additional data file.

    PubMed Central

    Morris, Samuel A.; Slawin, Alexandra M. Z.; Teat, Simon J.; Morris, Russell E.

    2016-01-01

    The synthesis and characterisation of five coordination polymers – Ni2(mip)2(H2O)8·2H2O (1), Zn6(mip)5(OH)2(H2O)4·7.4H2O (2), Zn6(mip)5(OH)2(H2O)2·4H2O (3), Mn(HMeOip)2 (4), and Mn3(tbip)2(Htbip)2(EtOH)2 (5) – are reported. Preliminary nitric oxide release data on compounds 2 and 3 are also given. PMID:27019640

  15. Reactivity of damaged pyrimidines: formation of a Schiff base intermediate at the glycosidic bond of saturated dihydrouridine.

    PubMed

    Jian, Yajun; Lin, Gengjie; Chomicz, Lidia; Li, Lei

    2015-03-11

    DNA glycosylases catalyze the first step of the base excision repair (BER) pathway. The chemistry used by these enzymes for deglycosylation has been largely considered as the chemistry of the oxocarbenium ion, e.g., direct rupture of the C1'-N1 bond resulting in an oxocarbenium ion intermediate. Here we present mechanistic studies revealing the 2'-deoxyribose isomerization and subsequent deglycosylation processes in two pyrimidine lesions: 5,6-dihydro-2'-deoxyuridine (dHdU) and 5,6-dihydrothymidine (dHT), formed via ionizing radiation damage to 2'-deoxycytidine and thymidine, respectively, under anoxic conditions. Acid or heat treatment of these two lesions leads to the production of two pairs of C1' epimers containing a pyranose and a furanose, respectively, indicating that both lesions favor the rupture of the C1'-O4' bond, resulting in a Schiff base intermediate at the N-glycosidic bond. Such a Schiff base intermediate was trapped and characterized by either Pd-catalyzed hydrogenation or thiol-mediated addition reaction. In contrast, in undamaged 2'-deoxyuridine and thymidine, reactions at elevated temperatures lead to the release of nucleobases most likely via the traditional oxocarbenium ion pathway. DFT calculations further support the experimental findings, suggesting that the oxocarbenium ion intermediate is responsible for the deglycosylation process if the integrity of the pyrimidine ring is maintained, while the Schiff base intermediate is preferred if the C5═C6 bond is saturated. Currently, the oxocarbenium ion pathway is indicated to be solely responsible for the deglycosylation in BER enzymes, however our results suggest an alternative Schiff base mechanism which may be responsible for the repair of saturated pyrimidine damages.

  16. Aromatic Cations from Oxidative Carbon–Hydrogen Bond Cleavage in Bimolecular Carbon–Carbon Bond Forming Reactions

    PubMed Central

    Clausen, Dane J.

    2012-01-01

    Chromenes and isochromenes react quickly with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) to form persistent aromatic oxocarbenium ions through oxidative carbon–hydrogen cleavage. This process is tolerant of electron-donating and electron-withdrawing groups on the benzene ring and additional substitution on the pyran ring. A variety of nucleophiles can be added to these cations to generate a diverse set of structures. PMID:22780559

  17. Total synthesis of neopeltolide and analogs

    PubMed Central

    Cui, Yubo; Tu, Wangyang; Floreancig, Paul E.

    2010-01-01

    Neopeltolide, a potent cytotoxin from a Carribean sponge, was synthesized through a brief sequence that highlights the use of ethers as oxocarbenium ion precursors. Other key steps include an acid-mediated etherification and sequence that features a Sonogashira reaction, an intramolecular alkyne hydrosilylation reaction, and a Tamao oxidation. The alkene that is required for the oxidative cyclization can be hydrogenated to provide access to the natural product or an epimer, or can be epoxidized or dihydroxylated to form polar analogs. PMID:20697460

  18. A propos of glycosyl cations and the mechanism of chemical glycosylation; the current state of the art.

    PubMed

    Bohé, Luis; Crich, David

    2015-02-11

    An overview of recent advances in glycosylation with particular emphasis on mechanism is presented. The mounting evidence for both the existence of glycosyl oxocarbenium ions as fleeting intermediates in some reactions, and the crucial role of the associated counterion in others is discussed. The extremes of the SN1 and SN2 manifolds for the glycosylation reaction are bridged by a continuum of mechanisms in which it appears likely that most examples are located.

  19. A Propos of Glycosyl Cations and the Mechanism of Chemical Glycosylation; the Current State of the Art

    PubMed Central

    Bohé, Luis

    2014-01-01

    An overview of recent advances in glycosylation with particular emphasis on mechanism is presented. The mounting evidence for both the existence of glycosyl oxocarbenium ions as fleeting intermediates in some reactions, and the crucial role of the associated in counter ion in others is discussed. The extremes of the SN1 and SN2 manifolds for the glycosylation reaction are bridged by a continuum of mechanisms in which it appears likely that most examples are located. PMID:25108484

  20. Aspects of glycosidic bond formation in aqueous solution: chemical bonding and the role of water.

    PubMed

    Stubbs, John M; Marx, Dominik

    2005-04-22

    A model of the specific acid-catalyzed glycosidic bond formation in liquid water at ambient conditions is studied based on constrained Car-Parrinello ab initio molecular dynamics. Specifically the reaction of alpha-D-glucopyranose and methanol is found to proceed by a D(N)A(N) mechanism. The D(N) step consists of a concerted protonation of the O(1) hydroxyl leaving group; this process results in the breaking of the C(1)-O(1) bond, and oxocarbenium ion formation involving C(1)=O(5). The second step, A(N), is the formation of the C(1)-O(m) glycosidic bond, deprotonation of the methanol hydroxyl group O(m)H(m), and re-formation of the C(1)-O(5) single bond. A focus of this study is the analysis of the electronic structure during this condensed phase reaction relying on both Boys/Wannier localized orbitals and the electron localization function ELF. This analysis allows the clear elucidation of the chemical bonding features of the intermediate bracketed by the D(N) and A(N) steps, which is a non-solvent equilibrated oxocarbenium cation. Most interestingly, it is found that the oxygen in the pyranose ring becomes "desolvated" upon double bond/oxocarbenium formation, whereas it is engaged in the hydrogen-bonded water network before and after this period. This demonstrates that hydrogen bonding and thus the aqueous solvent play an active role in this reaction implying that microsolvation studies in the gas phase, both theoretical and experimental, might lead to qualitatively different reaction mechanisms compared to solution.

  1. Racemization in Prins Cyclization Reactions

    PubMed Central

    Jasti, Ramesh

    2008-01-01

    Isotopic labeling experiments were performed in order to elucidate a new mechanism for racemization in Prins cyclization reactions. The loss in optical activity for these reactions was shown to occur by 2-oxonia-Cope rearrangements by way of a (Z)-oxocarbenium ion intermediate. Reaction conditions such as solvent, temperature, and the nucleophile employed played a critical role in whether an erosion in enantiomeric excess was observed. Additionally, certain structural features of Prins cyclization precursors were also shown to be important for preserving optical purity in these reactions. PMID:17031979

  2. Glycosyl Cations versus Allylic Cations in Spontaneous and Enzymatic Hydrolysis.

    PubMed

    Danby, Phillip M; Withers, Stephen G

    2017-08-09

    Enzymatic prenyl and glycosyl transfer are seemingly unrelated reactions that yield molecules and protein modifications with disparate biological functions. However, both reactions employ diphosphate-activated donors and each proceed via cationic species: allylic cations and oxocarbenium ions, respectively. In this study, we explore the relationship between these processes by preparing valienyl ethers to serve as glycoside mimics that are capable of allylic rather than oxocarbenium cation stabilization. Rate constants for spontaneous hydrolysis of aryl glycosides and their analogous valienyl ethers were found to be almost identical, as were the corresponding activation enthalpies and entropies. This close similarity extended to the associated secondary kinetic isotope effects (KIEs), indicating very similar transition state stabilities and structures. Screening a library of over 100 β-glucosidases identified a number of enzymes that catalyze hydrolysis of these valienyl ethers with kcat values up to 20 s(-1). Detailed analysis of one such enzyme showed that ether hydrolysis occurs via the analogous mechanisms found for glycosides, and through a very similar transition state. This suggests that the generally lower rates of enzymatic cleavage of the cyclitol ethers reflects evolutionary specialization of these enzymes toward glycosides rather than inherent reactivity differences.

  3. The role of enzyme distortion in the single displacement mechanism of family 19 chitinases

    PubMed Central

    Brameld, Ken A.; Goddard, William A.

    1998-01-01

    By using molecular dynamics simulations, we have examined the binding of a hexaNAG substrate and two potential hydrolysis intermediates (an oxazoline ion and an oxocarbenium ion) to a family 19 barley chitinase. We find the hexaNAG substrate binds with all sugars in a chair conformation, unlike the family 18 chitinase which causes substrate distortion. Glu 67 is in a position to protonate the anomeric oxygen linking sugar residues D and E whereas Asn 199 serves to hydrogen bond with the C2′ N-acetyl group of sugar D, thus preventing the formation of an oxazoline ion intermediate. In addition, Glu 89 is part of a flexible loop region allowing a conformational change to occur within the active site to bring the oxocarbenium ion intermediate and Glu 89 closer by 4–5 Å. A hydrolysis product with inversion of the anomeric configuration occurs because of nucleophilic attack by a water molecule that is coordinated by Glu 89 and Ser 120. Issues important for the design of inhibitors specific to family 19 chitinases over family 18 chitinases also are discussed. PMID:9539727

  4. Photo-alteration of hydantoins against UV light and its relevance to prebiotic chemistry

    NASA Astrophysics Data System (ADS)

    Sarker, Palash K.; Takahashi, Jun-ichi; Obayashi, Yumiko; Kaneko, Takeo; Kobayashi, Kensei

    2013-06-01

    Aqueous solutions of 5-substituted hydantoins were irradiated with ultraviolet (UV) light, to investigate their structural stability against UV radiation as well as the possible photolysis products. The photolysis products were identified and the degree of photolysis was measured using reversed-phase and ion-exchange high-performance liquid chromatography. Hydantoin (2,4-imidazolidinedione) was dominantly detected as a photolysis product of 5-substituted hydantoins. With hydrolysis of UV-irradiated 5-substituted hydantoins, glycine and alanine were dominantly detected. These experimental results are important for the prebiotic photochemistry of 5-substituted hydantoins in the formation of hydantoin since they have been detected in Solar System materials.

  5. 32 CFR 724.701 - Composition.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... grade of Lieutenant Commander/Major with preference being given to senior grades. (c) Normally, at least three of the five members of the NDRB shall belong to the service from which the applicant whose case is...

  6. 32 CFR 724.701 - Composition.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... grade of Lieutenant Commander/Major with preference being given to senior grades. (c) Normally, at least three of the five members of the NDRB shall belong to the service from which the applicant whose case is...

  7. An Experimental and Computational Approach to Defining Structure/Reactivity Relationships for Intramolecular Addition Reactions to Bicyclic Epoxonium Ions

    PubMed Central

    Wan, Shuangyi; Gunaydin, Hakan; Houk, K. N.; Floreancig, Paul E.

    2008-01-01

    In this manuscript we report that oxidative cleavage reactions can be used to form oxocarbenium ions that react with pendent epoxides to form bicyclic epoxonium ions as an entry to the formation of cyclic oligoether compounds. Bicyclic epoxonium ion structure was shown to have a dramatic impact on the ratio of exo- to endo-cyclization reactions, with bicyclo[4.1.0] intermediates showing a strong preference for endo-closures and bicyclo[3.1.0] intermediates showing a preference for exo-closures. Computational studies on the structures and energetics of the transition states using the B3LYP/6-31G(d) method provide substantial insight into the origins of this selectivity. PMID:17547399

  8. Quantum Mechanics/Molecular Mechanics Study of the Sialyltransferase Reaction Mechanism.

    PubMed

    Hamada, Yojiro; Kanematsu, Yusuke; Tachikawa, Masanori

    2016-10-11

    The sialyltransferase is an enzyme that transfers the sialic acid moiety from cytidine 5'-monophospho-N-acetyl-neuraminic acid (CMP-NeuAc) to the terminal position of glycans. To elucidate the catalytic mechanism of sialyltransferase, we explored the potential energy surface along the sialic acid transfer reaction coordinates by the hybrid quantum mechanics/molecular mechanics method on the basis of the crystal structure of sialyltransferase CstII. Our calculation demonstrated that CstII employed an SN1-like reaction mechanism via the formation of a short-lived oxocarbenium ion intermediate. The computational barrier height was 19.5 kcal/mol, which reasonably corresponded with the experimental reaction rate. We also found that two tyrosine residues (Tyr156 and Tyr162) played a vital role in stabilizing the intermediate and the transition states by quantum mechanical interaction with CMP.

  9. A Novel Metabolic Pathway for Glucose Production Mediated by α-Glucosidase-catalyzed Conversion of 1,5-Anhydrofructose*

    PubMed Central

    Kim, Young-Min; Saburi, Wataru; Yu, Shukun; Nakai, Hiroyuki; Maneesan, Janjira; Kang, Min-Sun; Chiba, Seiya; Kim, Doman; Okuyama, Masayuki; Mori, Haruhide; Kimura, Atsuo

    2012-01-01

    α-Glucosidase is in the glycoside hydrolase family 13 (13AG) and 31 (31AG). Only 31AGs can hydrate the d-glucal double bond to form α-2-deoxyglucose. Because 1,5-anhydrofructose (AF), having a 2-OH group, mimics the oxocarbenium ion transition state, AF may be a substrate for α-glucosidases. α-Glucosidase-catalyzed hydration produced α-glucose from AF, which plateaued with time. Combined reaction with α-1,4-glucan lyase and 13AG eliminated the plateau. Aspergillus niger α-glucosidase (31AG), which is stable in organic solvent, produced ethyl α-glucoside from AF in 80% ethanol. The findings indicate that α-glucosidases catalyze trans-addition. This is the first report of α-glucosidase-associated glucose formation from AF, possibly contributing to the salvage pathway of unutilized AF. PMID:22613728

  10. Pheophorbide b ethyl ester from a chlorella vulgaris dietary supplement.

    PubMed

    Chee, Chin Fei; Rahman, Noorsaadah Abdul; Zain, Sharifuddin M; Ng, Seik Weng

    2008-09-24

    In the title compound, C(37)H(38)N(4)O(6), four five-membered nitro-gen-bearing rings are nearly coplanar. Two N atoms in two these five-membered rings have attached H atoms, which contribute to the formation of intra-molecular N-H⋯N hydrogen bonds [N⋯N = 2.713 (5)-3.033 (6) Å].

  11. The growth of phenanthrene from naphthalene by C2H2 additions

    NASA Astrophysics Data System (ADS)

    Bauschlicher, Charles W., Jr.

    2015-07-01

    Two paths are investigated for the growth of phenanthrene from naphthalene by the addition of C2H2 groups. The first series of steps leads to acenaphthylene (ACN), which is consistent with the path found previously. The addition of C2H2 to ACN can yield a product with two adjacent five-membered rings. Opening one five-membered ring produces a five-membered ring with CH2 side group. This can be converted to a six-membered ring in a manner analogous to the hydrogen atom catalysed fulvene to benzene conversion. A second path, with a somewhat higher barrier, can also lead to the phenanthrene product. The transition state for the second path is essentially isoenergetic with the stating material of ACN + C2H2 + H.

  12. Crystal structure of 3-meth-oxy-carbonyl-2-(4-meth-oxy-phen-yl)-8-oxo-1-aza-spiro[4.5]deca-1,6,9-trien-1-ium-1-olate.

    PubMed

    Martins, Lucimara Julio; Simoni, Deborah de Alencar; Aparicio, Ricardo; Coelho, Fernando

    2014-11-01

    The title compound, C18H17NO5, was prepared by a synthetic strategy based on the Heck reaction from Morita-Baylis-Hillman adducts. The five-membered ring adopts a slightly twisted conformation on the Ca-Cm (a = aromatic and m = methyl-ene) bond. The dihedral angle between the five-membered ring and the spiro aromatic ring is 89.35 (7)°; that between the five-membered ring and the 4-meth-oxy-benzene ring is 4.65 (7)°. Two short intra-molecular C-H⋯O contacts occur. In the crystal, mol-ecules are linked by C-H⋯O hydrogen bonds to generate a three-dimensional network.

  13. ANAEROBIC BIODEGRADATION OF NITROGEN-SUBSTITUTED AND SULFONATED BENZENE AQUIFER CONTAMINANTS (JOURNAL)

    EPA Science Inventory

    A literature survey of ground water contaminants indicated that aquifers are repositories for hazardous wastes, including N- and 5-substituted benzene derivatives. We therefore examined the susceptibility of several anilines, benzamides, benenesulfonic acids and benenesulfonamide...

  14. ANAEROBIC BIODEGRADATION OF NITROGEN-SUBSTITUTED AND SULFONATED BENZENE AQUIFER CONTAMINANTS (JOURNAL)

    EPA Science Inventory

    A literature survey of ground water contaminants indicated that aquifers are repositories for hazardous wastes, including N- and 5-substituted benzene derivatives. We therefore examined the susceptibility of several anilines, benzamides, benenesulfonic acids and benenesulfonamide...

  15. [N-(Carboxylatomethyl)aspartato(3-)](ethylenediamine)cobalt(III) trihydrate.

    PubMed

    Maderová, Jana; Marek, Jaromír; Pavelcík, Frantisek

    2003-05-01

    The mononuclear title complex, [Co(C(6)H(6)NO(6))(C(2)H(8)N(2))].3H(2)O, contains an octahedrally coordinated Co(III) atom. The N-(carboxymethyl)aspartate moiety is coordinated as a tetradentate ligand, providing an OONO-donor set and forming two trans five-membered chelate rings and one six-membered chelate ring. A seven-membered chelate ring is also formed, which consists of part of the six-membered chelate ring and part of one of the five-membered chelate rings. The crystal structure of the complex is stabilized by hydrogen bonds with three water molecules.

  16. Trimethyl-3-meth­oxy-4-oxo-5-triphenyl­phospho­ranyl­idene­cyclo­pent-1-ene-1,2,3-tricarboxyl­ate

    PubMed Central

    Krawczyk, Krzysztof K.; Wojtasiewicz, Krystyna; Maurin, Jan K.; Gronowska, Ewa; Czarnocki, Zbigniew

    2010-01-01

    The title compound, C30H27O8P (2), was formed as one of two products {(1) [Krawczyk et al. (2010 ▶). Acta Cryst. E66 (cv2752)] and (2)} in the reaction of dimethyl acetyl­enedicarboxyl­ate with triphenyl­phosphine. The mol­ecule of (2) consists of a five-membered carbocyclic ring. The P atom is a part of a triphenylphosphoranylidene substituent. In contrast to (1), the five-membered ring of (2) is planar, the r.m.s. deviation being only 0.009 (2) Å. PMID:21588989

  17. 7 CFR 1220.213 - Establishment and membership.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... soybean production. (c) Cooperator Organization representation on the Committee shall consist of five members elected by the Cooperator Organization Board of Directors. The Cooperator Organization shall... elected by the Board and 5 producers elected by the Cooperator Organization. (b) Board representation on...

  18. 4 CFR 27.1 - The Board.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 4 Accounts 1 2014-01-01 2013-01-01 true The Board. 27.1 Section 27.1 Accounts GOVERNMENT... § 27.1 The Board. The Government Accountability Office Personnel Appeals Board, hereinafter the Board, is composed of five members appointed by the Comptroller General, in accordance with the provisions...

  19. 17 CFR 200.10 - The Commission.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 3 2014-04-01 2014-04-01 false The Commission. 200.10 Section... The Commission. The Commission is composed of five members, not more than three of whom may be members of the same political party. The members are appointed by the President, with the advice and consent...

  20. 10 CFR 1.11 - The Commission.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false The Commission. 1.11 Section 1.11 Energy NUCLEAR REGULATORY COMMISSION STATEMENT OF ORGANIZATION AND GENERAL INFORMATION Headquarters § 1.11 The Commission. (a) The Nuclear Regulatory Commission, composed of five members, one of whom is designated by the...

  1. 4 CFR 27.1 - The Board.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 4 Accounts 1 2013-01-01 2013-01-01 false The Board. 27.1 Section 27.1 Accounts GOVERNMENT... § 27.1 The Board. The Government Accountability Office Personnel Appeals Board, hereinafter the Board, is composed of five members appointed by the Comptroller General, in accordance with the provisions...

  2. 4 CFR 27.1 - The Board.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 4 Accounts 1 2012-01-01 2012-01-01 false The Board. 27.1 Section 27.1 Accounts GOVERNMENT... § 27.1 The Board. The Government Accountability Office Personnel Appeals Board, hereinafter the Board, is composed of five members appointed by the Comptroller General, in accordance with the provisions...

  3. 4 CFR 27.1 - The Board.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 4 Accounts 1 2011-01-01 2011-01-01 false The Board. 27.1 Section 27.1 Accounts GOVERNMENT... § 27.1 The Board. The Government Accountability Office Personnel Appeals Board, hereinafter the Board, is composed of five members appointed by the Comptroller General, in accordance with the provisions...

  4. 17 CFR 200.10 - The Commission.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 2 2013-04-01 2013-04-01 false The Commission. 200.10 Section... The Commission. The Commission is composed of five members, not more than three of whom may be members of the same political party. The members are appointed by the President, with the advice and consent...

  5. 17 CFR 200.10 - The Commission.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 2 2011-04-01 2011-04-01 false The Commission. 200.10 Section... The Commission. The Commission is composed of five members, not more than three of whom may be members of the same political party. The members are appointed by the President, with the advice and consent...

  6. 10 CFR 1.11 - The Commission.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false The Commission. 1.11 Section 1.11 Energy NUCLEAR REGULATORY COMMISSION STATEMENT OF ORGANIZATION AND GENERAL INFORMATION Headquarters § 1.11 The Commission. (a) The Nuclear Regulatory Commission, composed of five members, one of whom is designated by the...

  7. 17 CFR 200.10 - The Commission.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 2 2012-04-01 2012-04-01 false The Commission. 200.10 Section... The Commission. The Commission is composed of five members, not more than three of whom may be members of the same political party. The members are appointed by the President, with the advice and consent...

  8. The Reluctant Thinker and the Uses of Voice Parody in the Classroom.

    ERIC Educational Resources Information Center

    Airaudi, Jesse T.

    Student writers should be encouraged to move beyond a "jargon" or "public discourse" model of writing. This can be accomplished by capitalizing on the students' knack for imitation by turning it into public parody. After being divided into small panels of three, four, or five members, students are assigned a voice and topic and asked to develop a…

  9. Synthesis and characterization of estolide esters containing epoxy and cyclic carbonate groups

    USDA-ARS?s Scientific Manuscript database

    The unsaturated sites in oleic 2-ethylhexyl estolide esters (containing 35% monoenic fatty acids) were converted into epoxide and five-membered cyclic carbonate groups and the products characterized by Fourier transform infrared spectra (FTIR), 1H-, and 13C-nuclear magnetic resonance (NMR) spectrosc...

  10. The Curriculum Development Project for the Medical Laboratory Technology Program at Miami-Dade Junior College, Miami, Florida. Final Report.

    ERIC Educational Resources Information Center

    Miami-Dade Junior Coll., FL. Div. of Allied Health Studies.

    During Phase I of an Allied Health Professions Basic Improvement Grant, a five-member committee developed a curriculum for a medical laboratory technology program at Miami-Dade Junior College by: (1) defining competencies which differentiate a certified laboratory assistant from a medical laboratory technician, (2) translating expected laboratory…

  11. 26 CFR 1.382-3 - Definitions and rules relating to a 5-percent shareholder.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... increases or decreases its ownership of stock of the loss corporation relative to its percentage ownership... corporation relative to its percentage ownership interest at the close of November 19, 1990, by five... members of Public L. Because there is a shift of more than fifty percentage points in the ownership of...

  12. 26 CFR 1.382-3 - Definitions and rules relating to a 5-percent shareholder.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... increases or decreases its ownership of stock of the loss corporation relative to its percentage ownership... corporation relative to its percentage ownership interest at the close of November 19, 1990, by five... members of Public L. Because there is a shift of more than fifty percentage points in the ownership of...

  13. 26 CFR 1.382-3 - Definitions and rules relating to a 5-percent shareholder.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... increases or decreases its ownership of stock of the loss corporation relative to its percentage ownership... corporation relative to its percentage ownership interest at the close of November 19, 1990, by five... members of Public L. Because there is a shift of more than fifty percentage points in the ownership of...

  14. Rural electrification in Bangladesh: management, engineering, and financial assessment

    SciTech Connect

    Deverick, B.; Gellerson, M.; Stovall, J.; Shelton, R.

    1986-07-01

    This report represents the partial findings of a five-member, multidisciplinary team requested by USAID to assess the progress of the Rural Electrification Program in Bangladesh. Four areas are assessed in this report: the effectiveness of the management system; the system planning and engineering capabilities; RE tariffs and energy sector pricing policies; and the effectiveness of technical assistance.

  15. The phytochrome family: dissection of functional roles and signalling pathways among family members.

    PubMed Central

    Quail, P H

    1998-01-01

    There is considerable evidence that individual members of the five-membered phytochrome family of photoreceptors in Arabidopsis have differential functional roles in controlling plant photomorphogenesis. Emerging genetic evidence suggests that this differential activity may involve initially separate signalling pathway branches specific to individual family members. PMID:9800202

  16. Causality: School Libraries and Student Success (CLASS). White Paper

    ERIC Educational Resources Information Center

    American Association of School Librarians, 2014

    2014-01-01

    On April 11 and 12, 2014, the American Association of School Librarians (AASL) held "Causality: School Libraries and Student Success" (CLASS), an IMLS-funded national forum. Dr. Thomas Cook, one of the most influential methodologists in education research, and a five member panel of expert scholars and practitioners led 50 established…

  17. Extending the short and long wavelength limits of bacteriochlorin near-infrared absorption via dioxo- and bisimide-functionalization.

    PubMed

    Vairaprakash, Pothiappan; Yang, Eunkyung; Sahin, Tuba; Taniguchi, Masahiko; Krayer, Michael; Diers, James R; Wang, Alfred; Niedzwiedzki, Dariusz M; Kirmaier, Christine; Lindsey, Jonathan S; Bocian, David F; Holten, Dewey

    2015-03-26

    Six new bacteriochlorins expanding the range of the strong near-infrared (NIR) absorption (Qy band) to both shorter and longer wavelengths (∼690 to ∼900 nm) have been synthesized and characterized. The architectures include bacteriochlorin-bisimides that have six-membered imide rings spanning the 3,5- and 13,15-macrocycle positions or five-membered imide rings spanning the β-pyrrolic 2,3- and 12,13-positions. Both bisimide types absorb at significantly longer wavelength than the bacteriochlorin precursors (no fused rings), whereas oxo-groups at the 7- or 7,17-positions shift the Qy band to a new short wavelength limit. Surprisingly, bacteriochlorin-bisimides with five-membered β-pyrrolic-centered imide rings have a Qy band closer to that of six-membered bacteriochlorin-monoimides. However, the five-membered bisimides (versus the six-membered bacteriochlorin-monoimides) have significantly enhanced absorption intensity that is paralleled by an ∼2-fold higher fluorescence yield (∼0.16 vs ∼0.07) and longer singlet excited-state lifetime (∼4 ns vs ∼2 ns). The photophysical enhancements derive in part from mixing of the lowest unoccupied frontier molecular orbitals of the five-membered imide ring with those of the bacteriochlorin framework. In general, all of the new bacteriochlorins have excited-state lifetimes (1-4 ns) that are sufficiently long for use in molecular-based systems for photochemical applications.

  18. A Delicate Balance: Scientific Communication vs. National Security.

    ERIC Educational Resources Information Center

    Wallerstein, Mitchel B., Ed.; Gould, Stephen B., Ed.

    1987-01-01

    Provides the statements of the representatives of five member countries of the Coordinating Committee on Multilateral Export Control (CoCom) regarding the dissemination of government-sponsored research. Includes textual statements from representatives of the United Kingdom, France, the Federal Republic of Germany, Japan, and the United States. (TW)

  19. Crystal structure of 7,7-dimethyl-6-methyl-idenetri-cyclo-[6.2.1.0(1,5)]undecane-2-carb-oxy-lic acid.

    PubMed

    Beghidja, Noureddine; Benayache, Samir; Benayache, Fadila; Knight, David W; Kariuki, Benson M

    2015-02-01

    In the title compound, C15H22O2, both five-membered rings display an envelope conformation whereas the six-membered ring displays a chair conformation. In the crystal, pairs of O-H⋯O hydrogen bonds between carb-oxy-lic groups link mol-ecules, related by a twofold rotation axis, into supra-molecular dimers.

  20. A general and efficient palladium-catalyzed carbonylative synthesis of 2-aryloxazolines and 2-aryloxazines from aryl bromides.

    PubMed

    Wu, Xiao-Feng; Neumann, Helfried; Neumann, Stephan; Beller, Matthias

    2012-10-22

    Oxazoline is OK! A general and efficient method for the synthesis of oxazolines has been developed. This allowed the preparation of 27 five-membered-ring heterocycles and 11 six-membered-ring heterocycles in moderate to good yields. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Remembering Nancy. 25 Members of the Montessori Community Share Their Reflections on the Death of the AMS Founder.

    ERIC Educational Resources Information Center

    Turner, Joy; And Others

    1995-01-01

    Twenty-five members of the Montessori community share their memories of Dr. Nancy McCormick Rambusch, charismatic founder of the American Montessori movement, early childhood professional, and innovative educator, who died of pancreatic cancer on October 27, 1994. Rambusch's work of 40 years now flowers as an institutionalized educational program…

  2. Ligand iron catalysts for selective hydrogenation

    DOEpatents

    Casey, Charles P.; Guan, Hairong

    2010-11-16

    Disclosed are iron ligand catalysts for selective hydrogenation of aldehydes, ketones and imines. A catalyst such as dicarbonyl iron hydride hydroxycyclopentadiene) complex uses the OH on the five member ring and hydrogen linked to the iron to facilitate hydrogenation reactions, particularly in the presence of hydrogen gas.

  3. 10 CFR 7.2 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Definitions. 7.2 Section 7.2 Energy NUCLEAR REGULATORY...). Commission means the Nuclear Regulatory Commission of five members, or a quorum thereof, sitting as a body, as provided by section 201 of the Energy Reorganization Act of 1974, 42 U.S.C. 5841, (88 Stat....

  4. 10 CFR 7.2 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Definitions. 7.2 Section 7.2 Energy NUCLEAR REGULATORY...). Commission means the Nuclear Regulatory Commission of five members, or a quorum thereof, sitting as a body, as provided by section 201 of the Energy Reorganization Act of 1974, 42 U.S.C. 5841, (88 Stat....

  5. 10 CFR 7.2 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false Definitions. 7.2 Section 7.2 Energy NUCLEAR REGULATORY...). Commission means the Nuclear Regulatory Commission of five members, or a quorum thereof, sitting as a body, as provided by section 201 of the Energy Reorganization Act of 1974, 42 U.S.C. 5841, (88 Stat....

  6. 10 CFR 7.2 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Definitions. 7.2 Section 7.2 Energy NUCLEAR REGULATORY...). Commission means the Nuclear Regulatory Commission of five members, or a quorum thereof, sitting as a body, as provided by section 201 of the Energy Reorganization Act of 1974, 42 U.S.C. 5841, (88 Stat....

  7. 10 CFR 13.2 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Definitions. 13.2 Section 13.2 Energy NUCLEAR REGULATORY... to 5 U.S.C. 3344. Authority means the Nuclear Regulatory Commission. Authority head means the Commission of five members or a quorum thereof sitting as a body, as provided by section 201 of the...

  8. 10 CFR 7.2 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Definitions. 7.2 Section 7.2 Energy NUCLEAR REGULATORY...). Commission means the Nuclear Regulatory Commission of five members, or a quorum thereof, sitting as a body, as provided by section 201 of the Energy Reorganization Act of 1974, 42 U.S.C. 5841, (88 Stat....

  9. STS-29 MS Bagian during post landing egress exercises in JSC FFT mockup

    NASA Image and Video Library

    1989-01-19

    S89-25704 (Feb 1989) --- Astronaut James P. Bagian, STS-29 mission specialist, works his way down to "safety" using a Sky-genie device during emergency egress training for his five-member crew. Three other crewmembers watch in the background and await their turns with the rehearsal. The training took place in the Johnson Space Center's Shuttle mockup and integration laboratory.

  10. Institutional Self Study in Support of Reaffirmation of Accreditation.

    ERIC Educational Resources Information Center

    El Camino Coll., Torrance, CA.

    El Camino College, California, is a public two-year college in the South Bay area of Los Angeles County. The El Camino College District encompasses 5 high school districts, 12 elementary school districts and nine cities, with a population of almost 1 million. The district is governed by a five-member Board of Trustees, each representing one of the…

  11. A Day in the Life of the Gonzalez Family.

    ERIC Educational Resources Information Center

    Van Duzer, Carol; Burt, Miriam

    This multimedia, integrated educational package offers high beginning through intermediate adult English language learners (ELLs) an opportunity to develop communication skills and acquire cultural content knowledge relevant to their daily lives. The videotape and accompanying textbook and teacher's guide focus on the five members of an immigrant…

  12. Vouchers: Yea or Nay.

    ERIC Educational Resources Information Center

    Rouk, Ullik

    2000-01-01

    This report from the Southwest Educational Development Laboratory (SEDL) examines the status of publicly funded voucher programs, issues affecting the voucher movement, and program research. No legislature in the five member states served by SEDL has adopted vouchers, but several private programs are in place. Proponents claim vouchers offer an…

  13. Exploring the Cautionary Attitude toward Wikipedia in Higher Education: Implications for Higher Education Institutions

    ERIC Educational Resources Information Center

    Bayliss, Gemma

    2013-01-01

    This article presents the research findings of a small-scale study which aimed to explore the cautionary attitude toward the use of Wikipedia in the process of learning. A qualitative case study approach was taken, using literature review, institutional documentation, and semi-structured interviews with five members of academic teaching staff from…

  14. Synthesis and electronic properties of polycyclic aromatic hydrocarbons doped with phosphorus and sulfur.

    PubMed

    Delaunay, W; Szűcs, R; Pascal, S; Mocanu, A; Bouit, P-A; Nyulászi, L; Hissler, M

    2016-02-07

    In this work, we report on the synthesis of polyaromatic hydrocarbons containing phosphole and thiophene rings at the edge. The ring-closure reactions have been investigated by theoretical calculations. The optical and electrochemical properties and density functional theory calculations showed that the properties depend on the relative position of these five membered rings in the PAH structure.

  15. A Delicate Balance: Scientific Communication vs. National Security.

    ERIC Educational Resources Information Center

    Wallerstein, Mitchel B., Ed.; Gould, Stephen B., Ed.

    1987-01-01

    Provides the statements of the representatives of five member countries of the Coordinating Committee on Multilateral Export Control (CoCom) regarding the dissemination of government-sponsored research. Includes textual statements from representatives of the United Kingdom, France, the Federal Republic of Germany, Japan, and the United States. (TW)

  16. How to Add Philosophy Dimensions in Your Basic International Business Course

    ERIC Educational Resources Information Center

    Thanopoulos, John

    2010-01-01

    This article aims to assist professors in introducing concepts of self, philosophy, religions, the universe, existential dilemmas, etc., in their basic international business classes. Using active learning and five-member student teams, a student organized and administered conference adds a very useful dimension of knowledge sacrificing only one…

  17. 4 CFR 27.1 - The Board.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 4 Accounts 1 2010-01-01 2010-01-01 false The Board. 27.1 Section 27.1 Accounts GOVERNMENT... § 27.1 The Board. The Government Accountability Office Personnel Appeals Board, hereinafter the Board, is composed of five members appointed by the Comptroller General, in accordance with the provisions...

  18. 17 CFR 200.10 - The Commission.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false The Commission. 200.10 Section... The Commission. The Commission is composed of five members, not more than three of whom may be members of the same political party. The members are appointed by the President, with the advice and consent...

  19. 10 CFR 1.11 - The Commission.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false The Commission. 1.11 Section 1.11 Energy NUCLEAR REGULATORY COMMISSION STATEMENT OF ORGANIZATION AND GENERAL INFORMATION Headquarters § 1.11 The Commission. (a) The Nuclear Regulatory Commission, composed of five members, one of whom is designated by the...

  20. 7 CFR 1726.14 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... appropriate engineering study and RUS approval, for purposes of system financing, of the completion of all... committee means the committee consisting of three to five members representing the borrower's management and... registered or licensed person, who may be a staff employee or an outside consultant, to provide engineering...

  1. 40 CFR 26.1107 - IRB membership.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false IRB membership. 26.1107 Section 26.1107 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS Basic Ethical...-nursing Adults § 26.1107 IRB membership. (a) Each IRB shall have at least five members, with varying...

  2. 40 CFR 26.1107 - IRB membership.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false IRB membership. 26.1107 Section 26.1107 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS Basic Ethical...-nursing Adults § 26.1107 IRB membership. (a) Each IRB shall have at least five members, with varying...

  3. 32 CFR 865.107 - DRB composition and meeting location.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Section 865.107 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE ORGANIZATION AND MISSION-GENERAL PERSONNEL REVIEW BOARDS Air Force Discharge Review Board § 865.107 DRB composition and meeting location. (a) The DRB consists of five members, with the senior line officer acting...

  4. 32 CFR 865.107 - DRB composition and meeting location.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Section 865.107 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE ORGANIZATION AND MISSION-GENERAL PERSONNEL REVIEW BOARDS Air Force Discharge Review Board § 865.107 DRB composition and meeting location. (a) The DRB consists of five members, with the senior line officer acting...

  5. 49 CFR 800.2 - Organization.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 7 2014-10-01 2014-10-01 false Organization. 800.2 Section 800.2 Transportation... ORGANIZATION AND FUNCTIONS OF THE BOARD AND DELEGATIONS OF AUTHORITY Organization and Functions § 800.2 Organization. The Board consists of five Members appointed by the President with the advice and consent of...

  6. Needs of Older Employees and Retirees: Task Force Results of the Corporate Volunteerism Council of Minneapolis and St. Paul, Minnesota.

    ERIC Educational Resources Information Center

    Jecklin, Mary Jean; Fetter, Elizabeth A.

    The Twin Cities-based Corporate Volunteerism Council (CVC) sponsored the development and administration of a survey and focus groups in May through August, 1985, to determine the needs of older people before and after retirement. Twenty-five members of the CVC answered the survey. They replied that most companies offer preretirement planning and…

  7. A biomass derived N/C-catalyst for the electrochemical production of hydrogen peroxide.

    PubMed

    Yang, Yiran; He, Fei; Shen, Yanfei; Chen, Xinghua; Mei, Hao; Liu, Songqin; Zhang, Yuanjian

    2017-09-16

    Pomelo peel, a waste biomass, was used as an all-in-one (carbon source, self-template, and heteroatom) precursor to develop a nanoporous N/C-electrocatalyst for highly selective and energy-saving H2O2 production, in which disordered carbonous defects and five-membered rings (pyrrolic-N) played vital roles.

  8. A Secret Support Network

    ERIC Educational Resources Information Center

    Wasley, Paula

    2007-01-01

    This article describes Hanover College's Early Alert Team, an early-alert program that seeks to identify students' academic, social, or personal troubles as soon as they surface. The team's five members gather information about students from all corners of the campus and then devise strategies to help them. The early-alert system has not only…

  9. [3+2] Photooxygenation of aryl cylopropanes via visible light photocatalysis

    PubMed Central

    Lu, Zhan; Parrish, Jonathan D.; Yoon, Tehshik P.

    2014-01-01

    We report that Ru(bpz)32+ is an excellent sensitizer for the photooxygenation of aryl cyclopropanes upon irradiation with visible light. The effectiveness of this photocatalyst enables the synthesis of a range of five-membered endoperoxides in excellent yield with quite low (0.5 mol%) catalyst loadings even when standard household light sources are utilized. PMID:25170179

  10. Using WRF for Regional Climate Modeling: An Emphasis on the Southeast U.S. for Future Air Quality

    EPA Science Inventory

    This presentation describes preliminary analysis of a five-member regional climate ensemble (developed by AMAD and its contractors, including UNC) to determine if there is any consensus on projected changes to the placement of the North Atlantic Subtropical High (NASH, or Bermuda...

  11. Biotransformation of glabratephrin, a rare type of isoprenylated flavonoids, by Aspergillus niger.

    PubMed

    Mohamed, Abou-El-Hamd H; Khalafallah, Ali K; Yousof, Afifi H

    2008-01-01

    Microbial transformation of glabratephrin, the major isolated compound from Tephrosia purpurea, afforded pseudosemiglabrin. The formation of the transformed compound seems to be performed via ring opening-closure of a five-membered ring causing transformation from a spiro into a fused system. The structure of the transformed compound was determined by comprehensive NMR studies, including DEPT, COSY, HMQC, NOE and MS.

  12. 78 FR 18625 - Call for Nominations for the California Desert District Advisory Council

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-27

    ... Bureau of Land Management Call for Nominations for the California Desert District Advisory Council AGENCY...) California Desert District is soliciting nominations from the public for five members to serve 3-year terms on its Desert District Advisory Council. Council members provide advice and recommendations to...

  13. Classification of Vowels and Consonants by Individuals with Moderate Mental Retardation: Development of Arbitrary Relations via Match-to-Sample Training with Compound Stimuli.

    ERIC Educational Resources Information Center

    Lane, Scott D.; Critchfield, Thomas S.

    1998-01-01

    This study explored whether an identity-matching-based stimulus equivalence procedure could be used to teach vowel and consonant stimulus classes to two adolescent females with moderate mental retardation. Both participants acquired five-member classes of vowel and consonant stimuli, which subsequently generalized to vocal classification and to…

  14. Exploring the Drivers of Teacher Professionalism in Ghana

    ERIC Educational Resources Information Center

    Salifu, Inusah

    2015-01-01

    This research aimed to explore the working conditions teachers in the Ghana Education Service perceived as motivators in their professional practice. The research used mainly a qualitative approach and three focus groups of five members: each were organised with teacher participants drawn from the Ashanti Region purposively selected. The research…

  15. Current Updates on Oxazolidinone and Its Significance

    PubMed Central

    Pandit, Neha; Singla, Rajeev K.; Shrivastava, Birendra

    2012-01-01

    Oxazolidinone is a five-member heterocyclic ring exhibiting potential medicinal properties with preferential antibacterial activity. Scientists reported various synthetic procedures for this heterocyclic structure. Current review articles tried to cover each and every potential aspect of oxazolidinone like synthetic routes, pharmacological mechanism of action, medicinal properties, and current research activities. PMID:25954524

  16. Attitudes to Agricultural Policy and Farming Futures in the Context of the 2003 CAP Reform: A Comparison of Farmers in Selected Established and New Member States

    ERIC Educational Resources Information Center

    Gorton, Matthew; Douarin, Elodie; Davidova, Sophia; Latruffe, Laure

    2008-01-01

    Farmers' attitudes, to agricultural production, diversification and policy support, and behavioural intentions in five Member States of the EU (France, Lithuania, Slovakia, Sweden, England) are analysed comparatively. Groups of farmers with similarly held attitudes are identified using cluster analysis to investigate whether differences in…

  17. 14 CFR 1230.107 - IRB membership.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 5 2013-01-01 2013-01-01 false IRB membership. 1230.107 Section 1230.107 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION PROTECTION OF HUMAN SUBJECTS § 1230.107 IRB membership. (a) Each IRB shall have at least five members, with varying backgrounds to...

  18. 14 CFR 1230.107 - IRB membership.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 5 2011-01-01 2010-01-01 true IRB membership. 1230.107 Section 1230.107 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION PROTECTION OF HUMAN SUBJECTS § 1230.107 IRB membership. (a) Each IRB shall have at least five members, with varying backgrounds to...

  19. How to Create Lasting Change.

    ERIC Educational Resources Information Center

    Trusteeship, 1996

    1996-01-01

    Five members of the Commission on the Academic Presidency (Michael Schwartz, Garrey Caruthers, Mary Maples Dunn, Paul D. Schauer, Donald G. Phelps) reflect on how the commission's recommendations to public and higher education leaders can encourage meaningful, lasting change in college governance. Each speaks from a different policy perspective…

  20. 7 CFR 1215.21 - Establishment and membership.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Establishment and membership. 1215.21 Section 1215.21 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... Establishment and membership. (a) There is hereby established a Popcorn Board of five members. The number...

  1. 7 CFR 1c.107 - IRB membership.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 1 2012-01-01 2012-01-01 false IRB membership. 1c.107 Section 1c.107 Agriculture Office of the Secretary of Agriculture PROTECTION OF HUMAN SUBJECTS § 1c.107 IRB membership. (a) Each IRB shall have at least five members, with varying backgrounds to promote complete and adequate review...

  2. 45 CFR 690.107 - IRB membership.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 3 2013-10-01 2013-10-01 false IRB membership. 690.107 Section 690.107 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION PROTECTION OF HUMAN SUBJECTS § 690.107 IRB membership. (a) Each IRB shall have at least five members, with varying...

  3. 22 CFR 225.107 - IRB membership.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false IRB membership. 225.107 Section 225.107 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT PROTECTION OF HUMAN SUBJECTS § 225.107 IRB membership. (a) Each IRB shall have at least five members, with varying backgrounds to promote complete and...

  4. 15 CFR 27.107 - IRB membership.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 15 Commerce and Foreign Trade 1 2014-01-01 2014-01-01 false IRB membership. 27.107 Section 27.107 Commerce and Foreign Trade Office of the Secretary of Commerce PROTECTION OF HUMAN SUBJECTS § 27.107 IRB membership. (a) Each IRB shall have at least five members, with varying backgrounds to promote complete...

  5. 22 CFR 225.107 - IRB membership.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false IRB membership. 225.107 Section 225.107 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT PROTECTION OF HUMAN SUBJECTS § 225.107 IRB membership. (a) Each IRB shall have at least five members, with varying backgrounds to promote complete and...

  6. 49 CFR 11.107 - IRB membership.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 1 2014-10-01 2014-10-01 false IRB membership. 11.107 Section 11.107 Transportation Office of the Secretary of Transportation PROTECTION OF HUMAN SUBJECTS § 11.107 IRB membership. (a) Each IRB shall have at least five members, with varying backgrounds to promote complete and...

  7. 7 CFR 1215.21 - Establishment and membership.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Establishment and membership. 1215.21 Section 1215.21 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... Establishment and membership. (a) There is hereby established a Popcorn Board of five members. The number...

  8. 32 CFR 219.107 - IRB membership.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 2 2011-07-01 2011-07-01 false IRB membership. 219.107 Section 219.107 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS PROTECTION OF HUMAN SUBJECTS § 219.107 IRB membership. (a) Each IRB shall have at least five members,...

  9. 45 CFR 690.107 - IRB membership.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 3 2012-10-01 2012-10-01 false IRB membership. 690.107 Section 690.107 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION PROTECTION OF HUMAN SUBJECTS § 690.107 IRB membership. (a) Each IRB shall have at least five members, with varying...

  10. 34 CFR 97.107 - IRB membership.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 1 2014-07-01 2014-07-01 false IRB membership. 97.107 Section 97.107 Education Office of the Secretary, Department of Education PROTECTION OF HUMAN SUBJECTS Federal Policy for the... membership. (a) Each IRB shall have at least five members, with varying backgrounds to promote complete...

  11. 22 CFR 225.107 - IRB membership.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false IRB membership. 225.107 Section 225.107 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT PROTECTION OF HUMAN SUBJECTS § 225.107 IRB membership. (a) Each IRB shall have at least five members, with varying backgrounds to promote complete and...

  12. 7 CFR 1215.21 - Establishment and membership.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Establishment and membership. 1215.21 Section 1215.21 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... Establishment and membership. (a) There is hereby established a Popcorn Board of five members. The number...

  13. 7 CFR 1c.107 - IRB membership.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 1 2014-01-01 2014-01-01 false IRB membership. 1c.107 Section 1c.107 Agriculture Office of the Secretary of Agriculture PROTECTION OF HUMAN SUBJECTS § 1c.107 IRB membership. (a) Each IRB shall have at least five members, with varying backgrounds to promote complete and adequate review...

  14. 32 CFR 219.107 - IRB membership.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 2 2013-07-01 2013-07-01 false IRB membership. 219.107 Section 219.107 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS PROTECTION OF HUMAN SUBJECTS § 219.107 IRB membership. (a) Each IRB shall have at least five members,...

  15. 34 CFR 97.107 - IRB membership.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 1 2011-07-01 2011-07-01 false IRB membership. 97.107 Section 97.107 Education Office of the Secretary, Department of Education PROTECTION OF HUMAN SUBJECTS Federal Policy for the... membership. (a) Each IRB shall have at least five members, with varying backgrounds to promote complete...

  16. 38 CFR 16.107 - IRB membership.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false IRB membership. 16.107 Section 16.107 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS PROTECTION OF HUMAN SUBJECTS § 16.107 IRB membership. (a) Each IRB shall have at least five members, with varying...

  17. 15 CFR 27.107 - IRB membership.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 15 Commerce and Foreign Trade 1 2012-01-01 2012-01-01 false IRB membership. 27.107 Section 27.107 Commerce and Foreign Trade Office of the Secretary of Commerce PROTECTION OF HUMAN SUBJECTS § 27.107 IRB membership. (a) Each IRB shall have at least five members, with varying backgrounds to promote complete...

  18. 32 CFR 219.107 - IRB membership.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 2 2012-07-01 2012-07-01 false IRB membership. 219.107 Section 219.107 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS PROTECTION OF HUMAN SUBJECTS § 219.107 IRB membership. (a) Each IRB shall have at least five members,...

  19. 7 CFR 1215.21 - Establishment and membership.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Establishment and membership. 1215.21 Section 1215.21 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... Establishment and membership. (a) There is hereby established a Popcorn Board of five members. The number...

  20. 45 CFR 690.107 - IRB membership.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false IRB membership. 690.107 Section 690.107 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION PROTECTION OF HUMAN SUBJECTS § 690.107 IRB membership. (a) Each IRB shall have at least five members, with varying...

  1. 49 CFR 11.107 - IRB membership.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false IRB membership. 11.107 Section 11.107 Transportation Office of the Secretary of Transportation PROTECTION OF HUMAN SUBJECTS § 11.107 IRB membership. (a) Each IRB shall have at least five members, with varying backgrounds to promote complete and...

  2. Igniting Diversity: Actionable Methods and Ideas for Advancing Diversity in LIS Education in the US

    ERIC Educational Resources Information Center

    Lee, Shari A.; Chancellor, Renate; Chu, Clara M.; Rodriguez-Mori, Howard; Roy, Loriene

    2015-01-01

    The Association for Library and Information Science Education (ALISE) appointed a five-member Taskforce in 2011 to pursue the development of an ALISE Statement on Diversity. Two years later, the ALISE membership voted unanimously to adopt the statement. In an effort to move the statement from mere words on paper, the Taskforce provided actionable…

  3. 32 CFR 219.107 - IRB membership.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PROTECTION OF HUMAN SUBJECTS § 219.107 IRB membership. (a) Each IRB shall have at least five members, with... the institution. The IRB shall be sufficiently qualified through the experience and expertise of its... counsel in safeguarding the rights and welfare of human subjects. In addition to possessing the...

  4. An Assessment of the Basic Curriculum Guide for Teaching Vocational Agriculture in Texas.

    ERIC Educational Resources Information Center

    Brown, Herman D.

    The major purpose of this study was to revise the basic production agriculture curriculum guide used by vocational agrculture teachers in Texas. A twenty-five member advisory committee for curriculum revision conducted the following activities: (1) obtained thirty-one curriculum guides for a technical agriculture program, (2) surveyed vocational…

  5. Exploring the Drivers of Teacher Professionalism in Ghana

    ERIC Educational Resources Information Center

    Salifu, Inusah

    2015-01-01

    This research aimed to explore the working conditions teachers in the Ghana Education Service perceived as motivators in their professional practice. The research used mainly a qualitative approach and three focus groups of five members: each were organised with teacher participants drawn from the Ashanti Region purposively selected. The research…

  6. The Comprehensive Examination: Study Groups and Their Effectiveness--A Message to Counselor Education Faculty and Graduate Students

    ERIC Educational Resources Information Center

    Bartle, Lisa; Brodwin, Martin G.

    2006-01-01

    Counselor Education professors can assist students with comprehensive examination preparation. The first author, a graduate student in counseling, developed these ideas while studying for the comprehensive examination for the Master of Science degree program in counseling. All five members of her study group passed the examination the first time.

  7. The structure of N-arylindazoles and their aza-derivatives in the solid state: A systematic analysis of the Cambridge Structural Database coupled with DFT calculations

    NASA Astrophysics Data System (ADS)

    Alkorta, Ibon; Elguero, José

    2017-06-01

    A search in the Cambridge Structural Database for N-aryl indazoles and their aza derivatives affords 227 structures (183 1-aryl and 44 2-aryl). To discuss their structures, DFT calculations on 20 model compounds were carried out. The geometry of the five-membered ring (the pyrazole) and the conformation if the N-aryl substituent were analyzed.

  8. Recruiting and Developing HRDQ Reviewers: Why You Should Do It and What You Should Look For. Innovative Session.

    ERIC Educational Resources Information Center

    Squillaci, Christine M.; Russ-Eft, Darlene F.; Hatcher, Timothy G.; Rocco, Tonette S.; Yang, Baiyin

    The recruitment and development of reviewers for the Academy of Human Resource Development's (AHRD) research journal, "Human Resources Development Quarterly" (HRDQ), was examined at an innovative session of the 2002 AHRD conference. The session was conducted by five members of HRDQ's editorial board. The session objectives were as…

  9. Using WRF for Regional Climate Modeling: An Emphasis on the Southeast U.S. for Future Air Quality

    EPA Science Inventory

    This presentation describes preliminary analysis of a five-member regional climate ensemble (developed by AMAD and its contractors, including UNC) to determine if there is any consensus on projected changes to the placement of the North Atlantic Subtropical High (NASH, or Bermuda...

  10. 1'-Methyl-4'-[4-(trifluoro-meth-yl)phen-yl]dispiro-[indan-2,2'-pyrrolidine-3',2''-indan]-1,3,1''-trione.

    PubMed

    Wei, Ang Chee; Ali, Mohamed Ashraf; Choon, Tan Soo; Hemamalini, Madhukar; Fun, Hoong-Kun

    2011-11-01

    In the title compound, C(28)H(20)F(3)NO(3), the pyrrolidine ring adopts a half-chair conformation. The other five-membered rings adopt envelope conformations with the spiro and methylene C atoms as the flap atoms. In the crystal, mol-ecules are connected via weak C-H⋯O hydrogen bonds, forming sheets parallel to the bc plane.

  11. 22 CFR 67.2 - Board of Directors.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Board of Directors. 67.2 Section 67.2 Foreign... than thirteen and not more than twenty-five members reflecting the diversity of American society. The..., Washington, DC 20005-5000. (b) All major policy and funding decisions are made by the Board of Directors....

  12. How Should the "Ideal-Coach" Be? And How Is the "Real-Coach" Judged by the Athletes?

    ERIC Educational Resources Information Center

    Moser, Thomas

    1992-01-01

    Forty-five members of the Norwegian national team in orienteering and 11 coaches ranked 18 items regarding their importance in being a good coach. In addition, the athletes evaluated their individual coaches using the evaluation version of the scale. Compared responses of males and females, junior and senior athletes, and coaches and athletes. (KS)

  13. Space Shuttle Project

    NASA Image and Video Library

    1994-03-18

    Space Shuttle Columbia (STS-62) comes to a graceful halt with the help of a parachute after a 14-day mission. The five member crew performed materials processing experiments on the United States Microgravity Payload 2 (USMP-2), and also conducted experiments designed to enable or extend space flight technology aboard the Office of Aeornautics and Space Technology 2 payload (OAST-2).

  14. 4-Benzyl-6-bromo-2-phenyl-4H-imidazo[4,5-b]pyridine

    PubMed Central

    Ouzidan, Y.; Obbade, S.; Capet, F.; Essassi, El Mokhtar; Ng, Seik Weng

    2010-01-01

    The imidazopyridine fused ring in the title compound, C19H14BrN3, is almost coplanar with the phenyl ring at the 2-position of the five-membered ring [dihedral angle = 2.4 (1). The crystal structure features short Br⋯Br contacts [3.562 (1) Å]. PMID:21580750

  15. Desegregation in Birmingham, Alabama: A Case Study.

    ERIC Educational Resources Information Center

    Bynum, Effie; And Others

    In May 1974, a five member study team from Teachers College, Columbia University spent four and one-half days in Birmingham, Alabama, for the purpose of (1) collecting information that describes the desegregation process as it evolved, (2) interviewing principals, administrators, teachers, students and community leaders relative to their…

  16. Racemic methyl 3,10-dioxa-2-aza­tri­cyclo­[6.2.1.02,6]undecane-4-carboxyl­ate

    PubMed Central

    Moosa, Basem A.; Fazal, Atif; Ali, Shaikh A.; Fettouhi, Mohammed

    2011-01-01

    The structure of the racemic title compound, C10H15NO4, consists of a tricyclic skeleton comprising a six-membered piperidine ring and five-membered isoxazolidine and tetra­hydro­furan rings. The piperidine ring adopts a distorted chair conformation, while the isoxazolidine and tetra­hydro­furan rings have envelope conformations. PMID:21754538

  17. Trichodermin (4β-acet­oxy-12,13-epoxy­trichothec-9-ene)

    PubMed Central

    Chen, Shao-Yuan; Zhang, Chu-Long; Chen, Yu-Zhe; Lin, Fu-Cheng

    2008-01-01

    In the title natural product, C17H24O4, which is a very potent inhibitor of protein synthesis in mammalian cells, the five-membered ring displays an envelope conformation, whereas the two six-membered rings show different conformations, viz. chair and half-chair. PMID:21202093

  18. Convenient Synthesis of a Lactone, gamma-Butyrolactone

    NASA Astrophysics Data System (ADS)

    Bozak, Richard E.; Knittel, J.; Hicks, Ronald J.

    1998-01-01

    A five-membered cyclic ester, gamma-Butyrolactone, was prepared from GHB using a microscale reflux method. Cyclization yielded a product with a boiling point significantly greater (by 129 °C) than that of the open-chain analogue.

  19. New insights into thermal decomposition of polycyclic aromatic hydrocarbon oxyradicals.

    PubMed

    Liu, Peng; Lin, He; Yang, Yang; Shao, Can; Gu, Chen; Huang, Zhen

    2014-12-04

    Thermal decompositions of polycyclic aromatic hydrocarbon (PAH) oxyradicals on various surface sites including five-membered ring, free-edge, zigzag, and armchair have been systematically investigated by using ab initio density functional theory B3LYP/6-311+G(d,p) basis set. The calculation based on Hückel theory indicates that PAHs (3H-cydopenta[a]anthracene oxyradical) with oxyradicals on a five-membered ring site have high chemical reactivity. The rate coefficients of PAH oxyradical decomposition were evaluated by using Rice-Ramsperger-Kassel-Marcus theory and solving the master equations in the temperature range of 1500-2500 K and the pressure range of 0.1-10 atm. The kinetic calculations revealed that the rate coefficients of PAH oxyradical decomposition are temperature-, pressure-, and surface site-dependent, and the oxyradical on a five-membered ring is easier to decompose than that on a six-membered ring. Four-membered rings were found in decomposition of the five-membered ring, and a new reaction channel of PAH evolution involving four-membered rings is recommended.

  20. A Secret Support Network

    ERIC Educational Resources Information Center

    Wasley, Paula

    2007-01-01

    This article describes Hanover College's Early Alert Team, an early-alert program that seeks to identify students' academic, social, or personal troubles as soon as they surface. The team's five members gather information about students from all corners of the campus and then devise strategies to help them. The early-alert system has not only…

  1. A PROPOSED PROGRAM FOR A CURRICULUM DEVELOPMENT LABORATORY FOR UNEMPLOYED OUT-OF-SCHOOL YOUTH, 16 TO 21 YEARS OF AGE.

    ERIC Educational Resources Information Center

    FITZSIMMONS, JOHN J.; AND OTHERS

    A FIVE-MEMBER CONSULTANT TEAM, DURING THE SUMMER OF 1966, DEVELOPED A PROGRAM FOR OUT-OF-SCHOOL YOUTH WHICH WOULD RELATE WORK AND STUDY AND PROVIDE ON-THE-JOB TRAINING WITH THE ULTIMATE GOALS OF PLACING PARTICIPANTS IN SUITABLE VOCATIONS AND ASSISTING THEIR RETURN TO FORMAL EDUCATION LEADING TO A HIGH SCHOOL DIPLOMA. THIS PROPOSAL OUTLINES PROGRAM…

  2. Exploring the Cautionary Attitude toward Wikipedia in Higher Education: Implications for Higher Education Institutions

    ERIC Educational Resources Information Center

    Bayliss, Gemma

    2013-01-01

    This article presents the research findings of a small-scale study which aimed to explore the cautionary attitude toward the use of Wikipedia in the process of learning. A qualitative case study approach was taken, using literature review, institutional documentation, and semi-structured interviews with five members of academic teaching staff from…

  3. Single kernel method for detection of 2-acetyl-1-pyrroline in aromatic rice germplasm using SPME-GC/MS

    USDA-ARS?s Scientific Manuscript database

    INTRODUCTION Aromatic rice or fragrant rice, (Oryza sativa L.), has a strong popcorn-like aroma due to the presence of a five-membered N-heterocyclic ring compound known as 2-acetyl-1-pyrroline (2-AP). To date, existing methods for detecting this compound in rice require the use of several kernels. ...

  4. The Effect of Feedback on Group Cohesiveness.

    ERIC Educational Resources Information Center

    Mears, Peter M.

    The effect of feedback on group cohesiveness (measured in terms of group and task attractiveness) for a person who is performing a simple, highly repetitive task was studied. One hundred business administration students, randomly assigned to five member groups, completed a series of trials having the goal of determining the number commonly held by…

  5. Writing Assessment in the Department of Mathematics at Rochester Institute of Technology.

    ERIC Educational Resources Information Center

    Birken, Marcia

    The goal of writing assessment in the Department of Mathematics at Rochester Institute of Technology (RIT) is to assure that students can communicate about mathematics or statistics in a manner appropriate to their future careers. A five-member writing committee, composed of mathematics faculty, assess students at three different times during…

  6. Igniting Diversity: Actionable Methods and Ideas for Advancing Diversity in LIS Education in the US

    ERIC Educational Resources Information Center

    Lee, Shari A.; Chancellor, Renate; Chu, Clara M.; Rodriguez-Mori, Howard; Roy, Loriene

    2015-01-01

    The Association for Library and Information Science Education (ALISE) appointed a five-member Taskforce in 2011 to pursue the development of an ALISE Statement on Diversity. Two years later, the ALISE membership voted unanimously to adopt the statement. In an effort to move the statement from mere words on paper, the Taskforce provided actionable…

  7. 32 CFR 724.103 - NDRB panel.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 5 2010-07-01 2010-07-01 false NDRB panel. 724.103 Section 724.103 National... Definitions § 724.103 NDRB panel. An element of the NDRB, consisting of five members, authorized to review discharges. In plenary review session, an NDRB panel acts with the authority delegated by the Secretary...

  8. 45 CFR 46.107 - IRB membership.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Welfare Department of Health and Human Services GENERAL ADMINISTRATION PROTECTION OF HUMAN SUBJECTS Basic HHS Policy for Protection of Human Research Subjects § 46.107 IRB membership. (a) Each IRB shall have at least five members, with varying backgrounds to promote complete and adequate review of research...

  9. 45 CFR 46.107 - IRB membership.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROTECTION OF HUMAN SUBJECTS Basic HHS Policy for Protection of Human Research Subjects § 46.107 IRB membership. (a) Each IRB shall have at least five members, with varying backgrounds to promote complete and adequate review of research...

  10. JPRS Report, Near East and South Asia.

    DTIC Science & Technology

    1991-07-10

    detainees. The youngest is 22 and the eldest is 27. to lead them wisely," said one of the five members, who had short, curly hair and the stubble of a beard...In order to ensure the people enjoy quality standable given the ministerial ambitions of many of the goods, the government has to prevent adulteration

  11. Orono High School's Phase-Elective English Program.

    ERIC Educational Resources Information Center

    Larsen, David

    After completing a freshman course that provides instruction in basic skills and acquaints them with five members of the English staff, students at Orono High School, Maine, can select according to their interests from among 37 courses in diverse areas: folklore, film study, mythology, modern grammar, English literature, expository writing, and…

  12. Remembering Nancy. 25 Members of the Montessori Community Share Their Reflections on the Death of the AMS Founder.

    ERIC Educational Resources Information Center

    Turner, Joy; And Others

    1995-01-01

    Twenty-five members of the Montessori community share their memories of Dr. Nancy McCormick Rambusch, charismatic founder of the American Montessori movement, early childhood professional, and innovative educator, who died of pancreatic cancer on October 27, 1994. Rambusch's work of 40 years now flowers as an institutionalized educational program…

  13. 10 CFR 1.11 - The Commission.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false The Commission. 1.11 Section 1.11 Energy NUCLEAR.... (a) The Nuclear Regulatory Commission, composed of five members, one of whom is designated by the... for licensing and regulating nuclear facilities and materials and for conducting research in support...

  14. 10 CFR 1.11 - The Commission.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false The Commission. 1.11 Section 1.11 Energy NUCLEAR.... (a) The Nuclear Regulatory Commission, composed of five members, one of whom is designated by the... for licensing and regulating nuclear facilities and materials and for conducting research in support...

  15. 77 FR 66870 - Advisory Committee on Construction Safety and Health (ACCSH)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-07

    ... whenever the Agency proposes any safety or health standard that affects the construction industry. ACCSH... the construction industry--three employer representatives will be appointed; Five members who are similarly qualified to present the viewpoint of employees in the construction industry--three employee...

  16. 75 FR 19424 - Request for Nominations To Serve on the Advisory Committee on Construction Safety and Health (ACCSH)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-14

    ... proposes any safety or health standard that affects the construction industry. ACCSH operates in accordance... construction industry: Two employer representatives will be appointed; Five members who are similarly qualified to present the viewpoint of employees in the construction industry: Two employee representatives will...

  17. 75 FR 55610 - Advisory Committee on Construction Safety and Health (ACCSH)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-13

    ... whenever the Agency proposes any safety or health standard that affects the construction industry. ACCSH... the construction industry: three employer representatives will be appointed; Five members who are similarly qualified to present the viewpoint of employees in the construction industry: three employee...

  18. How to Add Philosophy Dimensions in Your Basic International Business Course

    ERIC Educational Resources Information Center

    Thanopoulos, John

    2010-01-01

    This article aims to assist professors in introducing concepts of self, philosophy, religions, the universe, existential dilemmas, etc., in their basic international business classes. Using active learning and five-member student teams, a student organized and administered conference adds a very useful dimension of knowledge sacrificing only one…

  19. The Effects of Assigned Role Versus Non-Assigned Role on Group Consensus.

    ERIC Educational Resources Information Center

    Gray, Philip A.

    1972-01-01

    Students in speech classes at Northern Illinois University participated in tests to determine what assumption of roles in discussion groups impairs participation and prohibits consensus. Students were randomly assigned to one of twelve discussion groups of five members each. The topic and materials for discussion were excerpted from the local…

  20. Needs of Older Employees and Retirees: Task Force Results of the Corporate Volunteerism Council of Minneapolis and St. Paul, Minnesota.

    ERIC Educational Resources Information Center

    Jecklin, Mary Jean; Fetter, Elizabeth A.

    The Twin Cities-based Corporate Volunteerism Council (CVC) sponsored the development and administration of a survey and focus groups in May through August, 1985, to determine the needs of older people before and after retirement. Twenty-five members of the CVC answered the survey. They replied that most companies offer preretirement planning and…

  1. Structural basis for the mechanistic understanding of human CD38-controlled multiple catalysis.

    PubMed

    Liu, Qun; Kriksunov, Irina A; Graeff, Richard; Munshi, Cyrus; Lee, Hon Cheung; Hao, Quan

    2006-10-27

    The enzymatic cleavage of the nicotinamide-glycosidic bond on nicotinamide adenine dinucleotide (NAD(+)) has been proposed to go through an oxocarbenium ion-like transition state. Because of the instability of the ionic intermediate, there has been no structural report on such a transient reactive species. Human CD38 is an ectoenzyme that can use NAD(+) to synthesize two calcium-mobilizing molecules. By using NAD(+) and a surrogate substrate, NGD(+), we captured and determined crystal structures of the enzyme complexed with an intermediate, a substrate, and a product along the reaction pathway. Our results showed that the intermediate is stabilized by polar interactions with the catalytic residue Glu(226) rather than by a covalent linkage. The polar interactions between Glu(226) and the substrate 2',3'-OH groups are essential for initiating catalysis. Ser(193) was demonstrated to have a regulative role during catalysis and is likely to be involved in intermediate stabilization. In addition, a product inhibition effect by ADP-ribose (through the reorientation of the product) or GDP-ribose (through the formation of a covalently linked GDP-ribose dimer) was observed. These structural data provide insights into the understanding of multiple catalysis and clues for drug design.

  2. Dissecting the mechanisms of a class of chemical glycosylation using primary 13C kinetic isotope effects

    NASA Astrophysics Data System (ADS)

    Huang, Min; Garrett, Graham E.; Birlirakis, Nicolas; Bohé, Luis; Pratt, Derek A.; Crich, David

    2012-08-01

    Although arguably the most important reaction in glycoscience, chemical glycosylations are among the least well understood of organic chemical reactions, resulting in an unnecessarily high degree of empiricism and a brake on rational development in this critical area. To address this problem, primary 13C kinetic isotope effects have now been determined for the formation of β- and α-manno- and glucopyranosides using a natural abundance NMR method. In contrast to the common current assumption, for three of the four cases studied the experimental and computed values are indicative of associative displacement of the intermediate covalent glycosyl trifluoromethanesulfonates. For the formation of the α-mannopyranosides, the experimentally determined KIE differs significantly from that computed for an associative displacement, which is strongly suggestive of a dissociative mechanism that approaches the intermediacy of a glycosyl oxocarbenium ion. The application of analogous experiments to other glycosylation systems should shed further light on their mechanisms and thus assist in the design of better reactions conditions with improved stereoselectivity.

  3. Dissecting the Mechanisms of a Class of Chemical Glycosylation Using Primary 13C Kinetic Isotope Effects

    PubMed Central

    Huang, Min; Garrett, Graham E.; Birlirakis, Nicolas; Bohé, Luis

    2012-01-01

    Although arguably the most important reaction in glycoscience, chemical glycosylations are among the least well understood of organic chemical reactions resulting in an unnecessarily high degree of empiricism and a brake on rational development in this critical area. To address this problem primary 13C kinetic isotope effects now have been determined for the formation of β- and α-manno- and glucopyranosides by a natural abundance NMR method. In contrast to the common current assumption, for three of the four cases studied the experimental values concur with those computed for associative displacement of the intermediate covalent glycosyl trifluoromethanesulfonates. For the formation of the α-mannopyranosides the experimentally determined KIE differs significantly from that computed for an associative displacement, which is strongly suggestive of a dissociative mechanism that approaches the intermediacy of a glycosyl oxocarbenium ion. The application of comparable experiments to other glycosylation systems should shed further light on their glycosylation mechanisms and thus assist in the design of better reactions conditions with improved stereoselectivity. PMID:22824899

  4. Studies of the Mechanism and Origins of Enantioselectivity for the Chiral Phosphoric Acid-Catalyzed Stereoselective Spiroketalization Reactions.

    PubMed

    Khomutnyk, Yaroslav Ya; Argüelles, Alonso J; Winschel, Grace A; Sun, Zhankui; Zimmerman, Paul M; Nagorny, Pavel

    2016-01-13

    Mechanistic and computational studies were conducted to elucidate the mechanism and the origins of enantiocontrol for asymmetric chiral phosphoric acid-catalyzed spiroketalization reactions. These studies were designed to differentiate between the S(N)1-like, S(N)2-like, and covalent phosphate intermediate-based mechanisms. The chiral phosphoric acid-catalyzed spiroketalization of deuterium-labeled cyclic enol ethers revealed a highly diastereoselective syn-selective protonation/nucleophile addition, thus ruling out long-lived oxocarbenium intermediates. Hammett analysis of the reaction kinetics revealed positive charge accumulation in the transition state (ρ = -2.9). A new computational reaction exploration method along with dynamics simulations supported an asynchronous concerted mechanism with a relatively short-lived polar transition state (average lifetime = 519 ± 240 fs), which is consistent with the observed inverse secondary kinetic isotope effect of 0.85. On the basis of these studies, a transition state model explaining the observed stereochemical outcome has been proposed. This model predicts the enantioselective formation of the observed enantiomer of the product with 92% ee, which matches the experimentally observed value.

  5. Transition state analysis of the arsenolytic depyrimidination of thymidine by human thymidine phosphorylase.

    PubMed

    Schwartz, Phillip A; Vetticatt, Mathew J; Schramm, Vern L

    2011-03-01

    Human thymidine phosphorylase (hTP) is responsible for thymidine (dT) homeostasis, promotes angiogenesis, and is involved in metabolic inactivation of antiproliferative agents that inhibit thymidylate synthase. Understanding its transition state structure is on the path to design transition state analogues. Arsenolysis of dT by hTP permits kinetic isotope effect (KIE) analysis of the reaction by forming thymine and the chemically unstable 2-deoxyribose 1-arsenate. The transition state for the arsenolytic reaction was characterized using multiple KIEs and computational analysis. Transition state analysis revealed a concerted bimolecular (A(N)D(N)) mechanism. A transition state constrained to match the intrinsic KIE values was found using density functional theory (B3LYP/6-31G*). An active site histidine is implicated as the catalytic base responsible for activation of the arsenate nucleophile and stabilization of the thymine leaving group during the isotopically sensitive step. At the transition state, the deoxyribose ring exhibits significant oxocarbenium ion character with bond breaking (r(C-N) = 2.45 Å) nearly complete and minimal bond making to the attacking nucleophile (r(C-O) = 2.95 Å). The transition state model predicts a deoxyribose conformation with a 2'-endo ring geometry. Transition state structure for the slow hydrolytic reaction of hTP involves a stepwise mechanism [Schwartz, P. A., Vetticatt, M. J., and Schramm, V. L. (2010) J. Am. Chem. Soc. 132, 13425-13433], in contrast to the concerted mechanism described here for arsenolysis.

  6. Revisit of the phenol O-glycosylation with glycosyl imidates, BF₃·OEt₂ is a better catalyst than TMSOTf.

    PubMed

    Li, Yali; Mo, Huaping; Lian, Gaoyan; Yu, Biao

    2012-12-01

    With BF(3)·OEt(2) as the catalyst, the glycosylation of phenols with glycosyl trichloroacetimidates (or N-phenyl trifluoroacetimidates) bearing 2-O-participating groups leads to the desired 1,2-trans-O-glycosides in generally excellent yields without formation of the 1,2-cis-anomers. However, with TMSOTf as the catalyst, the outcomes of the corresponding phenol O-glycosylation are highly dependent on the nucleophilicity of the phenols; less nucleophilic is the phenol, higher amounts of the 1,2-cis-O-glycoside together with more side-products are generated. 1,2-Orthoesters have been found to be the major products at a low temperature (<-70 °C) in all these phenol O-glycosylation reactions, which are transformed into the final products at a higher temperature. BF(3)·OEt(2) is an effective catalyst to promote the conversion of 1,2-orthoesters into the corresponding 1,2-trans-O-glycosides. However, the 1,2-orthoesters could be converted into the dioxolenium triflate and glycosyl triflate in the presence of TMSOTf, these intermediates which might be in equilibrium with the glycosyl oxocarbenium related species lead to the final mixture of the α/β-O-glycosides and side-products.

  7. An allolactose trapped at the lacZ β-galactosidase active site with its galactosyl moiety in a (4)H3 conformation provides insights into the formation, conformation, and stabilization of the transition state.

    PubMed

    Wheatley, Robert W; Huber, Reuben E

    2015-12-01

    When lactose was incubated with G794A-β-galactosidase (a variant with a "closed" active site loop that binds transition state analogs well) an allolactose was trapped with its Gal moiety in a (4)H3 conformation, similar to the oxocarbenium ion-like conformation expected of the transition state. The numerous interactions formed between the (4)H3 structure and β-galactosidase indicate that this structure is representative of the transition state. This conformation is also very similar to that of d-galactono-1,5-lactone, a good transition state analog. Evidence indicates that substrates take up the (4)H3 conformation during migration from the shallow to the deep mode. Steric forces utilizing His418 and other residues are important for positioning the O1 leaving group into a quasi-axial position. An electrostatic interaction between the O5 of the distorted Gal and Tyr503 as well as C-H-π bonds with Trp568 are also significant. Computational studies of the energy of sugar ring distortion show that the β-galactosidase reaction itinerary is driven by energetic considerations in utilization of a (4)H3 transition state with a novel (4)C1-(4)H3-(4)C1 conformation itinerary. To our knowledge, this is the first X-ray crystallographic structural demonstration that the transition state of a natural substrate of a glycosidase has a (4)H3 conformation.

  8. Structural analysis of substrate-mimicking inhibitors in complex with Neisseria meningitidis 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase - The importance of accommodating the active site water.

    PubMed

    Heyes, Logan C; Reichau, Sebastian; Cross, Penelope J; Jameson, Geoffrey B; Parker, Emily J

    2014-12-01

    3-Deoxy-d-arabino-heptulosonate 7-phosphate synthase (DAH7PS) catalyses the first committed step of the shikimate pathway, which produces the aromatic amino acids as well as many other aromatic metabolites. DAH7PS catalyses an aldol-like reaction between phosphoenolpyruvate and erythrose 4-phosphate. Three phosphoenolpyruvate mimics, (R)-phospholactate, (S)-phospholactate and vinyl phosphonate [(E)-2-methyl-3-phosphonoacrylate], were found to competitively inhibit DAH7PS from Neisseria meningitidis, which is the pathogen responsible for bacterial meningitis. The most potent inhibitor was the vinyl phosphonate with a Ki value of 3.9±0.4μM. We report for the first time crystal structures of these compounds bound in the active site of a DAH7PS enzyme which reveals that the inhibitors bind to the active site of the enzyme in binding modes that mimic those of the predicted oxocarbenium and tetrahedral intermediates of the enzyme-catalysed reaction. Furthermore, the inhibitors accommodate the binding of a key active site water molecule. Together, these observations provide strong evidence that this active site water participates directly in the DAH7PS reaction, enabling the facial selectivity of the enzyme-catalysed reaction sequence to be delineated.

  9. Crystal structures of Geobacillus stearothermophilus alpha-glucuronidase complexed with its substrate and products: mechanistic implications.

    PubMed

    Golan, Gali; Shallom, Dalia; Teplitsky, Anna; Zaide, Galia; Shulami, Smadar; Baasov, Timor; Stojanoff, Vivian; Thompson, Andy; Shoham, Yuval; Shoham, Gil

    2004-01-23

    Alpha-glucuronidases cleave the alpha-1,2-glycosidic bond between 4-O-methyl-d-glucuronic acid and short xylooligomers as part of the hemicellulose degradation system. To date, all of the alpha-glucuronidases are classified as family 67 glycosidases, which catalyze the hydrolysis via the investing mechanism. Here we describe several high resolution crystal structures of the alpha-glucuronidase (AguA) from Geobacillus stearothermophilus, in complex with its substrate and products. In the complex of AguA with the intact substrate, the 4-O-methyl-d-glucuronic acid sugar ring is distorted into a half-chair conformation, which is closer to the planar conformation required for the oxocarbenium ion-like transition state structure. In the active site, a water molecule is coordinated between two carboxylic acids, in an appropriate position to act as a nucleophile. From the structural data it is likely that two carboxylic acids, Asp(364) and Glu(392), activate together the nucleophilic water molecule. The loop carrying the catalytic general acid Glu(285) cannot be resolved in some of the structures but could be visualized in its "open" and "closed" (catalytic) conformations in other structures. The protonated state of Glu(285) is presumably stabilized by its proximity to the negative charge of the substrate, representing a new variation of substrate-assisted catalysis mechanism.

  10. Cation Clock Reactions for the Determination of Relative Reaction Kinetics in Glycosylation Reactions: Applications to Gluco- and Mannopyranosyl Sulfoxide and Trichloroacetimidate Type Donors

    PubMed Central

    Adero, Philip O.; Furukawa, Takayuki; Huang, Min; Mukherjee, Debaraj; Retailleau, Pascal; Bohé, Luis

    2015-01-01

    The development of a cation clock method based on the intramolecular Sakurai reaction for probing the concentration dependence of the nucleophile in glycosylation reactions is described. The method is developed for the sulfoxide and trichloroacetimidate glycosylation protocols. The method reveals that O-glycosylation reactions have stronger concentration dependencies than C-glycosylation reactions consistent with a more associative, SN2-like character. For the 4,6-O-benzylidene-directed mannosylation reaction a significant difference in concentration dependence is found for the formation of the β- and α-anomers suggesting a difference in mechanism and a rationale for the optimization of selectivity regardless of the type of donor employed. In the mannose series the cyclization reaction employed as clock results in the formation of cis and trans-fused oxabicyclo[4,4,0]decanes as products with the latter being strongly indicative of the involvement of a conformationally mobile transient glycosyl oxocarbenium ion. With identical protecting group arrays cyclization in the glucopyranose series is more rapid than in the mannopyranose manifold. The potential application of related clock reactions in other carbenium ion-based branches of organic synthesis is considered. PMID:26207807

  11. Crystal structure and snapshots along the reaction pathway of a family 51 α-l-arabinofuranosidase

    PubMed Central

    Hövel, Klaus; Shallom, Dalia; Niefind, Karsten; Belakhov, Valery; Shoham, Gil; Baasov, Timor; Shoham, Yuval; Schomburg, Dietmar

    2003-01-01

    High-resolution crystal structures of α-l-arabinofuranosidase from Geobacillus stearothermophilus T-6, a family 51 glycosidase, are described. The enzyme is a hexamer, and each monomer is organized into two domains: a (β/α)8-barrel and a 12-stranded β sandwich with jelly-roll topology. The structures of the Michaelis complexes with natural and synthetic substrates, and of the transient covalent arabinofuranosyl– enzyme intermediate represent two stable states in the double displacement mechanism, and allow thorough examination of the catalytic mechanism. The arabinofuranose sugar is tightly bound and distorted by an extensive network of hydrogen bonds. The two catalytic residues are 4.7 Å apart, and together with other conserved residues contribute to the stabilization of the oxocarbenium ion-like transition state via charge delocalization and specific protein–substrate interactions. The enzyme is an anti-protonator, and a 1.7 Å electrophilic migration of the anomeric carbon takes place during the hydrolysis. PMID:14517232

  12. Synthesis and reactivity of aliphatic sulfur pentafluorides from substituted (pentafluorosulfanyl)benzenes.

    PubMed

    Vida, Norbert; Václavík, Jiří; Beier, Petr

    2016-01-01

    Oxidation of 3- and 4-pentafluorosulfanyl-substituted anisoles and phenols with hydrogen peroxide and sulfuric acid provided a mixture of SF5-substituted muconolactone, maleic, and succinic acids. A plausible mechanism for the formation of the aliphatic SF5 compounds was presented and their chemical reactivity was investigated. SF5-substituted para-benzoquinone was synthesized; its oxidation led to an improved yield of 2-(pentafluorosulfanyl)maleic acid. The reaction of SF5-substituted maleic anhydride and para-benzoquinone with cyclopentadiene afforded the Diels-Alder adducts. Decomposition of 3-(pentafluorosulfanyl)muconolactone in acidic, neutral and basic aqueous media was investigated and the decarboxylation of 2-(pentafluorosulfanyl)maleic acid provided 3-(pentafluorosulfanyl)acrylic acid.

  13. Synthesis and reactivity of aliphatic sulfur pentafluorides from substituted (pentafluorosulfanyl)benzenes

    PubMed Central

    Vida, Norbert; Václavík, Jiří

    2016-01-01

    Summary Oxidation of 3- and 4-pentafluorosulfanyl-substituted anisoles and phenols with hydrogen peroxide and sulfuric acid provided a mixture of SF5-substituted muconolactone, maleic, and succinic acids. A plausible mechanism for the formation of the aliphatic SF5 compounds was presented and their chemical reactivity was investigated. SF5-substituted para-benzoquinone was synthesized; its oxidation led to an improved yield of 2-(pentafluorosulfanyl)maleic acid. The reaction of SF5-substituted maleic anhydride and para-benzoquinone with cyclopentadiene afforded the Diels–Alder adducts. Decomposition of 3-(pentafluorosulfanyl)muconolactone in acidic, neutral and basic aqueous media was investigated and the decarboxylation of 2-(pentafluorosulfanyl)maleic acid provided 3-(pentafluorosulfanyl)acrylic acid. PMID:26877813

  14. [Equivalence classes formation applied to learning musical notes].

    PubMed

    Escuer Acín, Emilio; García García, Andrés; Bohórquez Zayas, Cristóbal; Gutiérrez Domínguez, Maria Teresa

    2006-02-01

    Three experiments involving training and application of equivalence classes were carried out. In the first of them, with 6-6 years old children, and applying the equivalence classes logic to musical symbols and sounds learning, the necessary relations to build three equivalence classes (do, mi, sol) of five members each were acquired. In second and third experiments, five and seven equivalence classes (musical notes) of five member each were obtained. Six and a half years old children and one 17 years old Down syndrome diagnosed child took part in them, respectively. Results highlight the theoretical meaning of equivalence classes as explanation of human symbolic behavior, as the educational incomes of improving learning of basic elements in artistic skills.

  15. The origin of global and macrocyclic aromaticity in porphyrinoids.

    PubMed

    Nakagami, Yuto; Sekine, Rika; Aihara, Jun-ichi

    2012-07-21

    The global and macrocyclic aromaticity of porphyrinoids was characterized using our graph theory of aromaticity. The sequential line plots of topological resonance energy (TRE) against the number of π-electrons (N(π)) for different porphyrinoids are similar with four major extrema to those for five-membered heterocycles. This supports the view that five-membered rings are the main origin of global aromaticity in porphyrinoids. Macrocyclic circuits contribute significantly to macrocyclic π-circulation but modestly to global aromaticity. Macrocyclic aromaticity/antiaromaticity in oligopyrrolic macrocycles can be predicted by formally applying Hückel's [4n + 2] rule to an annulene-like main macrocyclic conjugation pathway (MMCP). This bridged annulene model can be justified by examining the contribution of individual macrocyclic circuits to macrocyclic aromaticity. A Hückel-like rule of macrocyclic aromaticity was found for porphyrinoid species.

  16. Tetra­methyl 1,1,2-triphenyl-2H-1λ5-phosphole-2,3,4,5-tetra­carboxyl­ate

    PubMed Central

    Krawczyk, Krzysztof K.; Wojtasiewicz, Krystyna; Maurin, Jan K.; Gronowska, Ewa; Czarnocki, Zbigniew

    2010-01-01

    The title compound, C30H27O8P (1), was formed as one of two products {(1) and (2) [Krawczyk et al. (2010 ▶). Acta Cryst. E66 (cv2753)]} in the reaction of dimethyl acetyl­enedicarboxyl­ate with triphenyl­phosphine. The mol­ecule of (1) consists of a five-membered ring, in which the P atom is incorporated. One of the phenyl groups of the triphenyl­phosphine migrated to a vicinal C atom during the reaction. The five-membered ring of (1) is corrugated [r.m.s. deviation = 0.0719 (8) Å], whereas that in compound (2) is planar, the r.m.s. deviation being only 0.009 (2) Å. PMID:21588988

  17. Crystal structure of N′-[(E)-(1S,3R)-(3-isopropyl-1-methyl-2-oxo­cyclo­pent­yl)methyl­idene]-4-methyl­benzene­sulfono­hydrazide

    PubMed Central

    Tymann, David; Dragon, Dina Christina; Golz, Christopher; Preut, Hans; Strohmann, Carsten; Hiersemann, Martin

    2015-01-01

    The title compound, C17H24N2O3S, was synthesized in order to determine the relative configuration of the corresponding β-keto aldehyde. In the U-shaped mol­ecule, the five-membered ring approximates an envelope, with the methyl­ene C atom adjacent to the quaternary C atom being the flap, and the methyl and isopropyl substituents lying to the same side of the ring. The dihedral angles between the four nearly coplanar atoms of the five-membered ring and the flap and the aromatic ring are 35.74 (15) and 55.72 (9)°, respectively. The bond angles around the S atom are in the range from 103.26 (12) to 120.65 (14)°. In the crystal, mol­ecules are linked via N—H⋯O hydrogen bonds, forming a chain along the a axis. PMID:26870519

  18. Theoretical study of the decomposition of ethyl and ethyl 3-phenyl glycidate.

    PubMed

    Josa, Daniela; Peña-Gallego, Angeles; Rodríguez-Otero, Jesús; Cabaleiro-Lago, Enrique M

    2013-01-01

    The mechanism of the decomposition of ethyl and ethyl 3-phenyl glycidate in gas phase was studied by density functional theory (DFT) and MP2 methods. A proposed mechanism for the reaction indicates that the ethyl side of the ester is eliminated as ethylene through a concerted six-membered cyclic transition state, and the unstable intermediate glycidic acid decarboxylates rapidly to give the corresponding aldehyde. Two possible pathways for glycidic acid decarboxylation were studied: one via a five-membered cyclic transition state, and the other via a four-membered cyclic transition state. The results of the calculations indicate that the decarboxylation reaction occurs via a mechanism with five-membered cyclic transition state.

  19. Effects of meso-substituents and core-modification on photophysical and electrochemical properties of porphyrin-ferrocene conjugates

    NASA Astrophysics Data System (ADS)

    Rai, Smita; Gayatri, G.; Narahari Sastry, G.; Ravikanth, M.

    2008-12-01

    The effects of meso-substituents and porphyrin core-modification on electronic communication between ferrocene and porphyrin in covalently linked porphyrin-ferrocene conjugates are described. The electrochemical and photophysical studies indicated that the electronic communication between porphyrin and ferrocene is strong when meso-substituents are five membered aryl groups than six membered aryl groups. This may be traced to the near orthogonal arrangement of porphyrin ring with six membered meso-aryl groups leading to weaker interaction between the porphyrin and ferrocenyl groups in conjugates, while the five membered furyl and thienyl groups are closer to the porphyrin plane than being orthogonal. Molecular orbital studies are performed at semiempirical PM3 and BLYP levels to rationalize the results.

  20. Hydrogen bonding in the mechanism of GDP-mannose mannosyl hydrolase

    NASA Astrophysics Data System (ADS)

    Mildvan, A. S.; Xia, Z.; Azurmendi, H. F.; Legler, P. M.; Balfour, M. R.; Lairson, L. L.; Withers, S. G.; Gabelli, S. B.; Bianchet, M. A.; Amzel, L. M.

    2006-06-01

    GDP-mannose mannosyl hydrolase (GDPMH) from E. coli catalyzes the hydrolysis of GDP-α- D-sugars to GDP and β- D-sugars by nucleophilic substitution with inversion at the anomeric C1 of the sugar, with general base catalysis by His-124. The 1.3 Å X-ray structure of the GDPMH-Mg 2+-GDP complex was used to model the complete substrate, GDP-mannose into the active site. The substrate is linked to the enzyme by 12 hydrogen bonds, as well as by the essential Mg 2+. In addition, His-124 was found to participate in a hydrogen bonded triad: His-124-NδH⋯Tyr-127-OH⋯Pro-120(C dbnd6 O). The contributions of these hydrogen bonds to substrate binding and to catalysis were investigated by site-directed mutagenesis. The hydrogen bonded triad detected in the X-ray structure was found to contribute little to catalysis since the Y127F mutation of the central residue shows only 2-fold decreases in both kcat and Km. The GDP leaving group is activated by the essential Mg 2+ which contributes at least 10 5-fold to kcat, and by nine hydrogen bonds, including those from Tyr-103, Arg-37, Arg-52, and Arg-65 (via an intervening water), each of which contribute factors to kcat ranging from 24- to 309-fold. Both Arg-37 and Tyr-103 bind the β-phosphate of the leaving GDP and are only 5.0 Å apart. Accordingly, the R37Q/Y103F double mutant shows partially additive effects of the two single mutants on kcat, indicating cooperativity of Arg-37 and Tyr-103 in promoting catalysis. The extensive activation of the GDP leaving group suggests a mechanism with dissociative character with a cationic oxocarbenium-like transition state and a half-chair conformation of the sugar ring, as found with glycosidase enzymes. Accordingly, Asp-22 which contributes 10 2.1- to 10 2.6-fold to kcat, is positioned to both stabilize a developing cationic center at C1 and to accept a hydrogen bond from the C2-OH of the mannosyl group, and His-88, which contributes 10 2.3-fold to kcat, is positioned to accept

  1. Mission Specialist (MS) Fabian sleeps on middeck

    NASA Image and Video Library

    1983-06-24

    STS007-26-1439 (18-24 June 1983) --- Astronaut John M. Fabian, STS-7 mission specialist, is captured with a 35mm camera at his sleep station in the middeck of the Earth-orbiting space shuttle Challenger. This scene was selected by the five-member astronaut crew for showing at its July 1, 1983 Post Flight Press Conference (PFPC) at the Johnson Space Center's (JSC) main auditorium. Photo credit: NASA

  2. Activation of C-H bonds of arenes: selectivity and reactivity in bis(pyridyl) platinum(II) complexes.

    PubMed

    Zhang, Fenbao; Kirby, Christopher W; Hairsine, Douglas W; Jennings, Michael C; Puddephatt, Richard J

    2005-10-19

    The reaction of [PtMe2(NN)] and B(C6F5)3/H2O in CF3CH2OH with arenes Ar-H gives [PtAr{HOB(C6F5)3}(LL)] if the bis(pyridyl) ligand NN forms a six-membered, but not five-membered, chelate ring; methyl-substituted arenes give selectivity for metalation of meta > para > ortho, but methoxy-substituted arenes give ortho > meta, para.

  3. STS-69 crew prepares for landing

    NASA Image and Video Library

    1995-09-21

    STS069-343-014 (18 September 1995) --- Astronaut David M. Walker, mission commander, gets a hand from astronaut Michael L. Gernhardt as he gets into the partial-pressure launch and entry suit in preparation for landing. STS-69 and the Space Shuttle Endeavour, with a five-member crew, launched on September 7, 1995, from the Kennedy Space Center (KSC). The multifaceted mission ended September 18, 1995, with a successful landing on Runway 33 at KSC.

  4. STS-37 Gamma Ray Observatory (GRO) held by RMS over OV-104's payload bay

    NASA Image and Video Library

    1991-04-07

    STS037-99-098 (7 April 1991) --- Backdropped against clouds over water, the Gamma Ray Observatory (GRO) is still in the grasp of the Space Shuttle Atlantis' Remote Manipulator System (RMS) in this 70mm scene. A special Extravehicular Activity (EVA) was required by astronauts Jerry L. Ross and Jerome (Jay) Apt to manually extend the high-gain antenna on GRO. The five-member crew capped off a busy Flight Day 3 by releasing the heavy payload.

  5. A silaproline-containing dipeptide.

    PubMed

    Vivet, B; Cavelier, F; Martinez, J; Didierjean, C; Marraud, M; Aubry, A

    2000-12-01

    The silaproline-containing dipeptide N-(3, 3-dimethyl-1-pivaloyl-1-aza-3-sila-5-cyclopentylcarbonyl)-L- alanine isopropylamide, C(17)H(33)N(3)O(3)Si, has two independent molecules in the asymmetric unit and each adopts a beta-II folded conformation, where the amide on the terminal C interacts intramolecularly with the pivaloyl O atom. The five-membered silaproline ring is C(beta)-puckered, an infrequent conformation for the homologous proline ring.

  6. Combining Silver Catalysis and Organocatalysis: A Sequential Michael Addition/Hydroalkoxylation One-Pot Approach to Annulated Coumarins

    PubMed Central

    2014-01-01

    A highly stereoselective one-pot procedure for the synthesis of five-membered annulated hydroxycoumarins has been developed. By merging primary amine catalysis with silver catalysis, a series of functionalized coumarin derivatives were obtained in good yields (up to 91%) and good to excellent enantioselectivities (up to 99% ee) via a Michael addition/hydroalkoxylation reaction. Depending on the substituents on the enynone, the synthesis of annulated six-membered rings is also feasible. PMID:25250728

  7. Muscarine, imidaozle, oxazole and thiazole alkaloids.

    PubMed

    Jin, Zhong

    2013-06-01

    Covering: July 2010 to June 2012. Previous review: Nat. Prod. Rep., 2011, 28, 1143-1191. Structurally diverse alkaloids containing five-membered heterocyclic subunits, such as imidazole, oxazole, thiazole, as well as their saturated congeners, are widely distributed in terrestrial and marine organisms and microorganisms. These naturally occurring secondary metabolites often exhibit extensive and pharmacologically important biological activities. The latest progress involving isolation, biological activities, chemical synthetic studies, and biosynthetic pathways of these natural products has been summarized in this review.

  8. Board Duty in Retirement

    ERIC Educational Resources Information Center

    Goodman, Richard H.

    2007-01-01

    At 75, encouraged by an 18-year veteran board member who decided to seek election to the state legislature, the author decided to run for election to the five-member regional school board that represents the voters in the four-town New Hampshire seacoast. He had been superintendent of a five-town area in New Hampshire and in the Boston suburb of…

  9. 2-(4-Ethoxy­benzyl­idene)butanoic acid

    PubMed Central

    Muhammad, Niaz; Tahir, M. Nawaz; Zia-ur-Rehman; Ali, Saqib

    2008-01-01

    In the crystal structure of the title compound, C13H16O3, dimers are formed due to inter­molecular O—H⋯O hydrogen bonding. There exists an intra­molecular C—H⋯O hydrogen bond which forms a five-membered ring. There is also present a C—H⋯π inter­action between a methyl CH group of an ethyl group and the centroid of the aromatic ring. PMID:21203172

  10. (3+2)-Cycloaddition Reactions of Oxyallyl Cations

    PubMed Central

    Li, Hui; Wu, Jimmy

    2014-01-01

    The (3+2)-cycloaddition reaction involving oxyallyl cations has proven to be a versatile and efficient approach for the construction of five-membered carbo- and heterocycles, which are prevalent frameworks in natural products and pharmaceuticals. The following article will provide a brief summary of recent disclosures on this process featuring chemo-, regio- and diastereoselective oxyallyl cycloadditions with both electron-rich and electron-deficient 2π partners. PMID:25598556

  11. 1-Dichloro­acetyl-8a-methyl-1,2,3,4,6,7,8,8a-octa­hydro­pyrrolo­[1,2-a]pyrimidin-6-one

    PubMed Central

    Gao, Shuang; Zhao, Li-xia; Ye, Fei; Fu, Ying; Xing, Zhi-yong

    2012-01-01

    In the title compound, C10H14Cl2N2O2, the five-membered ring adopts an envelope conformation (with the methylene C atom closest to the C—N bridge as the flap), while the conformation of the six-membered ring is close to a twist-boat. In the crystal, mol­ecules are linked by weak C—H⋯O hydrogen bonds, forming chains along the c-axis direction. PMID:22807815

  12. 2,2-Dichloro-1-(3,3,6-trimethyl-9-oxo-1,5-diaza­bicyclo­[4.3.0]nonan-5-yl)ethanone

    PubMed Central

    Fu, Ying; Ye, Fei

    2011-01-01

    In the title mol­ecule, C12H18Cl2N2O2, the six-membered ring is in a chair conformation and the five-membered ring is in an envelope conformation. In the crystal, weak inter­molecular bifurcated (C—H)2⋯O hydrogen bonds connect mol­ecules into chains along [010]. PMID:22091051

  13. Proliferation Control Regimes: Background and Status

    DTIC Science & Technology

    2008-01-31

    and, eventually, two 1000-megawatt, light water nuclear reactors.10 North Korea received shipments CRS-15 10 (...continued) Latest Developments, by...heavy water reactor, ratify and implement the Additional Protocol and implement transparency measures. On June 6, 2006, the permanent five members of the...inalienable right to peaceful nuclear energy, assistance in building state-of-the-art light water reactors for Iran, a peaceful nuclear cooperation agreement

  14. Synthesis of cyclic alkenylsiloxanes by semihydrogenation: a stereospecific route to (Z)-alkenyl polyenes.

    PubMed

    Elbert, Bryony L; Lim, Diane S W; Gudmundsson, Haraldur G; O'Hanlon, Jack A; Anderson, Edward A

    2014-07-07

    Cyclic alkenylsiloxanes were synthesized by semihydrogenation of alkynylsilanes-a reaction previously plagued by poor stereoselectivity. The silanes, which can be synthesized on multigram scale, undergo Hiyama-Denmark coupling to give (Z)-alkenyl polyene motifs found in bioactive natural products. The ring size of the silane is crucial: five-membered cyclic siloxanes also couple under fluoride-free conditions, whilst their six-membered homologues do not, enabling orthogonality within this structural motif.

  15. Crystal structure of methyl 3'-benzamido-4'-(4-meth-oxy-phen-yl)-1'-methyl-spiro-[indeno-[1,2-b]quinoxaline-11,2'-pyrrolidine]-3'-carboxyl-ate.

    PubMed

    Chandralekha, Kuppan; Sureshbabu, Adukamparai Rajukrishnan; Gavaskar, Deivasigamani; Lakshmi, Srinivasakannan

    2016-09-01

    In the title compound, C35H30N4O3, the spiro C atom connects the five-membered pyrrolidine ring and the indeno-quinoxaline ring system. The pyrrolidine ring adopts a twist conformation. An intra-molecular N-H⋯N inter-action between the amino group and the pyrazine ring is observed. In the crystal, mol-ecules are linked by a pairs of C-H⋯O hydrogen bonds, forming inversion dimers.

  16. STS-34 Galileo spacecraft / inertial upper stage (IUS) deployment

    NASA Image and Video Library

    1989-10-18

    STS034-72-070 (18 Oct 1989) --- Backdropped against the blackness of space, the Galileo spacecraft and its inertial upper stage (IUS) begin relative separation from the Earth-orbiting Space Shuttle Atlantis. The five-member STS-34 crew deployed the Jupiter-bound satellite within six hours of achieving Earth orbit on Oct. 18, 1989. The scene was exposed with a 70mm handheld Hasselblad camera.

  17. STS 51-L crewmembers briefed during training session

    NASA Technical Reports Server (NTRS)

    1986-01-01

    Five members of the STS 51-L crew and a backup crewmember are briefed during a training session in JSC's Shuttle mockup and integration laboratory. From left to right are Astronauts Ellison S. Onizuka, mission specialist; Ronald E. McNair, mission specialist; Gregory Jarvis, Hughes payload specialist; Judith A. Resnik, mission specialist; Sharon Christa McAuliffe, citizen observer/payload specialist representing the Teacher in Space project. Barbara R. Morgan, backup to McAuliffe, is in the right foreground.

  18. Rhodium-Catalyzed NH-Indole-Directed C-H Carbonylation with Carbon Monoxide: Synthesis of 6H-Isoindolo[2,1-a]indol-6-ones.

    PubMed

    Huang, Qiufeng; Han, Qingshuai; Fu, Shurong; Yao, Zizhu; Su, Lv; Zhang, Xiaofeng; Lin, Shen; Xiang, Shengchang

    2016-12-16

    An efficient synthesis of 6H-isoindolo[2,1-a]indol-6-ones through rhodium-catalyzed NH-indole-directed C-H carbonylation of 2-arylindoles with carbon monoxide has been developed. Preliminary mechanistic studies revealed that this reaction proceeds via N-H bond cleavage and subsequent C-H bond cleavage. Reaction monitoring via ESI-MS was used to support the formation of five-membered rhodacycle species in the catalytic cycle.

  19. 4,4,5,5-Tetra­methyl-1,3,2λ5-dioxa­phospho­lan-2-one

    PubMed Central

    Skarżyńska, Anna; Trzeciak, Anna M.; Gniewek, Andrzej

    2011-01-01

    The five-membered ring in the title compound, C6H13O3P, exists in an envelope conformation with one of the ring C atoms at the flap position. The coordination geometry around the P atom is a distorted tetra­hedron. The crystal structure is stabilized by several weak C—H⋯O and P—H⋯O hydrogen bonds, forming a three-dimensional network. PMID:22091172

  20. 16-Oxa-penta-cyclo-[6.6.5.0(1,18).0(2,7).0(9,14)]nona-deca-2,4,6,9,11,13,18-heptaen-15-one.

    PubMed

    Mathew, Eason M; Sithambaresan, M; Unnikrishnan, P A; Kurup, M R Prathapachandra

    2014-02-01

    In the title compound, C18H12O2, the benzene rings are inclined to one another by 66.79 (7)°. The five-membered ring is almost planar with a maximum deviation of 0.014 (1) Å. In the crystal, the mol-ecules are linked by pairs of weak C-H⋯O interactions into centrosymmetric dimers. These dimers are linked by C-H⋯π interactions, forming a three-dimensional structure.

  1. Synthesis of Cyclic Alkenylsiloxanes by Semihydrogenation: A Stereospecific Route to (Z)-Alkenyl Polyenes

    PubMed Central

    Elbert, Bryony L; Lim, Diane S W; Gudmundsson, Haraldur G; O'Hanlon, Jack A; Anderson, Edward A

    2014-01-01

    Cyclic alkenylsiloxanes were synthesized by semihydrogenation of alkynylsilanes—a reaction previously plagued by poor stereoselectivity. The silanes, which can be synthesized on multigram scale, undergo Hiyama–Denmark coupling to give (Z)-alkenyl polyene motifs found in bioactive natural products. The ring size of the silane is crucial: five-membered cyclic siloxanes also couple under fluoride-free conditions, whilst their six-membered homologues do not, enabling orthogonality within this structural motif. PMID:24899240

  2. 2-[4-Acetyl-5-(biphenyl-4-yl)-4,5-dihydro-1,3,4-oxadiazol-2-yl]phenyl acetate

    PubMed Central

    Yehye, Wagee A.; Ariffin, Azhar; Rahman, Noorsaadah Abdul; Ng, Seik Weng

    2010-01-01

    In the title mol­ecule, C24H20N2O4, the five-membered oxadiazole ring is nearly planar (r.m.s. deviation = 0.053 Å) and the phenyl ring of the biphenyl unit attached to it forms a dihedral angle of 73.2 (1)°; the other phenyl ring is close to coplanar with the oxadiazole ring [dihedral angle = 6.2 (2)°]. PMID:21580697

  3. An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

    PubMed Central

    2011-01-01

    Summary This review presents a comprehensive overview on selected synthetic routes towards commercial drug compounds as published in both journal and patent literature. Owing to the vast number of potential structures, we have concentrated only on those drugs containing five-membered heterocycles and focused principally on the assembly of the heterocyclic core. In order to target the most representative chemical entities the examples discussed have been selected from the top 200 best selling drugs of recent years. PMID:21647262

  4. Dominantly-inherited lop ears.

    PubMed

    Leung, Alexander K C; Kong, Albert Y F; Robson, W Lane M; McLeod, D Ross

    2007-10-01

    We describe a four-generation Chinese family that included five members who had an isolated bilateral lop ear anomaly. The presentation suggested a dominant mode of inheritance. The absence of male-to-male transmission does not exclude an X-linked dominant mode of inheritance. Since the phenotypic anomaly of the male proband was no more severe than the affected female members, an autosomal dominant mode of inheritance is most likely. 2007 Wiley-Liss, Inc

  5. 10-Formyl-2,4,6,8,12-penta­nitro-2,4,6,8,10,12-hexa­azatetra­cyclo­[5.5.0.03,11.05,9]dodeca­ne

    PubMed Central

    Jin, Shaohua; Chen, Shusen; Chen, Huaxiong; Li, Lijie; Shi, Yanshan

    2009-01-01

    The title compound, C7H7N11O11 (PNMFIW), is a caged heterocycle substituted with five nitro and one formyl groups. It is related to the hexa­azaisowurtzitane family of high-density high-energy polycyclic cage compounds. Four nitro groups are appended to the four N atoms of the two five-membered rings, while a nitro group and a formyl are attached to the two N atoms of the six-membered ring. PMID:21578838

  6. Combining silver catalysis and organocatalysis: a sequential Michael addition/hydroalkoxylation one-pot approach to annulated coumarins.

    PubMed

    Hack, Daniel; Chauhan, Pankaj; Deckers, Kristina; Hermann, Gary N; Mertens, Lucas; Raabe, Gerhard; Enders, Dieter

    2014-10-03

    A highly stereoselective one-pot procedure for the synthesis of five-membered annulated hydroxycoumarins has been developed. By merging primary amine catalysis with silver catalysis, a series of functionalized coumarin derivatives were obtained in good yields (up to 91%) and good to excellent enantioselectivities (up to 99% ee) via a Michael addition/hydroalkoxylation reaction. Depending on the substituents on the enynone, the synthesis of annulated six-membered rings is also feasible.

  7. 17-Deoxoestrone [estra-1,3,5(10)-trien-3-ol]–methanol (3/1)

    PubMed Central

    Ketuly, Kamal Aziz; Hadi, A. Hamid A.; Ng, Seik Weng; Tiekink, Edward R. T.

    2011-01-01

    Three independent mol­ecules of the title estrone derivative and a mol­ecule of methanol comprise the asymmetric unit of the title compound [systematic name: 13-methyl-6,7,8,9,11,12,13,14,15,16-deca­hydro­cyclo­penta­[a]phenanthren-3-ol–meth­an­ol (3/1)], 3C18H24O·CH3OH. Two of the estrone mol­ecules exhibit 50:50 disorder (one displays whole-mol­ecule disorder and the other partial disorder in the fused five- and six-membered rings) so that five (partial) mol­ecular conformations are discernable. The conformation of the six-membered ring abutting the aromatic ring is close to a half-chair in all five components. The conformation of the six-membered ring fused to the five-membered ring is based on a chair with varying degrees of distortion ranging from minor to significant. Two distinct conformations are found for the five-membered ring: in four mol­ecules, the five-membered ring is twisted about the bond linking it to the six-membered ring, and in the other, the five-membered ring is an envelope with the quaternary C atom being the flap atom. The crystal packing features O—H⋯O hydrogen bonding whereby the four mol­ecules comprising the asymmetric unit are linked into a supra­molecular chain along the b axis. PMID:21754468

  8. 1,3-Dibenzyl-6-bromo-1H-imidazo[4,5-b]pyridin-2(3H)-one

    PubMed Central

    Dahmani, S.; Kandri Rodi, Y.; Capet, F.; Essassi, El Mokhtar; Ng, Seik Weng

    2010-01-01

    The imidazopyridine fused-ring in the title compound, C20H16BrN3O, is planar (r.m.s. deviation = 0.011 Å). The phenyl rings of the benzyl substitutents twist away from the central five-membered ring in opposite directions; the rings are aligned at 61.3 (1) and 71.2 (1)° with respect to this ring. PMID:21580599

  9. STS 51-L crewmembers briefed during training session

    NASA Technical Reports Server (NTRS)

    1986-01-01

    Five members of the STS 51-L crew and a backup crewmember are briefed during a training session in JSC's Shuttle mockup and integration laboratory. From left to right are Astronauts Ellison S. Onizuka, mission specialist; Ronald E. McNair, mission specialist; Gregory Jarvis, Hughes payload specialist; Judith A. Resnik, mission specialist; Sharon Christa McAuliffe, citizen observer/payload specialist representing the Teacher in Space project. Barbara R. Morgan, backup to McAuliffe, is in the right foreground.

  10. 6α-Hy-droxy-5,6-dihydro-salviasperanol.

    PubMed

    Asik, Safra Izuani Jama; Razak, Ibrahim Abdul; Salae, Abdul Wahab; Chantrapromma, Suchada; Fun, Hoong-Kun

    2010-10-23

    In the title compound, C(20)H(28)O(4), a diterpenoid isolated from the roots of Premna obtusifolia (Verbenaceae), the five-membered ring is in a half-chair conformation. One six-membered ring exists in a twisted-boat conformation while the other is in half-boat conformation. The crystal packing is stabilized by inter-molecular O-H⋯O and weak C-H⋯O inter-actions, generating (001) sheets.

  11. 6α-Hy­droxy-5,6-dihydro­salviasperanol

    PubMed Central

    Asik, Safra Izuani Jama; Razak, Ibrahim Abdul; Salae, Abdul Wahab; Chantrapromma, Suchada; Fun, Hoong-Kun

    2010-01-01

    In the title compound, C20H28O4, a diterpenoid isolated from the roots of Premna obtusifolia (Verbenaceae), the five-membered ring is in a half-chair conformation. One six-membered ring exists in a twisted-boat conformation while the other is in half-boat conformation. The crystal packing is stabilized by inter­molecular O—H⋯O and weak C—H⋯O inter­actions, generating (001) sheets. PMID:21589076

  12. STS-32 Commander Brandenstein dons LES equipment in KSC LC Pad 39A white room

    NASA Image and Video Library

    1990-01-09

    STS032-S-062 (9 Jan 1990) --- Inside the White Room at Launch Pad 39A, a suit technician helps astronaut Daniel C. Brandenstein, mission commander, suit up for the launch of the orbiter Columbia on Shuttle Mission STS-32. Dubious weather at the return-to-launch site (RTLS) caused postponement of yesterday's planned launch. During the ten day mission, the five member crew is scheduled to deploy the SYNCOM IV-5 military communications satellite and retrieve the Long Duration Exposure Facility.

  13. Tasumatrols U-Z, taxane diterpene esters from Taxus sumatrana.

    PubMed

    Shen, Ya-Ching; Wang, Shih-Sheng; Chien, Ching-Te; Kuo, Yao-Haur; Khalil, Ashraf Taha

    2008-04-01

    Phytochemical investigation of the leaves and twigs of Taxus sumatrana afforded six new taxane diterpene esters, tasumatrols U-Z ( 1- 6). Compounds 2 and 5 contained a rare five-membered lactone ring at C-8, C-9, C-10, and C-19. The structures were established on the basis of detailed spectroscopic analyses, particularly HRESIMS and 2D NMR techniques. Compound 5 showed cytotoxicity against a human hepatoma (Hep2) cell line.

  14. Tetrazolium compounds: synthesis and applications in medicine.

    PubMed

    Wei, Cheng-Xi; Bian, Ming; Gong, Guo-Hua

    2015-03-27

    Tetrazoles represent a class of five-membered heterocyclic compounds with polynitrogen electron-rich planar structural features. This special structure makes tetrazole derivatives useful drugs, explosives, and other functional materials with a wide range of applications in many fields of medicine, agriculture, material science, etc. Based on our research works on azoles and other references in recent years, this review covers reported work on the synthesis and biological activities of tetrazole derivatives.

  15. Metal-Free Radical [2+2+1] Carbocyclization of Benzene-Linked 1,n-Enynes: Dual C(sp(3))-H Functionalization Adjacent to a Heteroatom.

    PubMed

    Hu, Ming; Fan, Jian-Hong; Liu, Yu; Ouyang, Xuan-Hui; Song, Ren-Jie; Li, Jin-Heng

    2015-08-10

    A new metal-free oxidative radical [2+2+1] carbocyclization of benzene-linked 1,n-enynes with two C(sp(3))-H bonds adjacent to the same heteroatom is described. This method achieves two C(sp(3))-H oxidative functionalizations and an annulation, thus providing efficient and general access to a variety of fused five-membered carbocyclic hydrocarbons.

  16. Area Handbook Series: Dominican Republic and Haiti: Country Studies

    DTIC Science & Technology

    1991-01-01

    elections could be held. The Permanent Electoral Council ( Conseil Electoral Permanent- CEP) scheduled local, legislative, and presidential elections for...Jean-Claude Duvalier fled in face of popu- lar revolt. He was succeeded by five-member National Council of Government ( Conseil National de...con- sented. After hastily naming a National Council of Government ( Conseil National de Gouvernement-CNG) made up of Nam- phy, Regala, and three

  17. Dichlorido{(E)-2,4,6-trimethyl-N-[phen­yl(2-pyridyl)methyl­idene]aniline-κ2 N,N′}palladium(II)

    PubMed Central

    Yang, Cheng-Hsien; Peng, Ya-Liu; Wang, Mei-Hua; Shih, Kuo-Chen; Hsueh, Mao-Lin

    2010-01-01

    The title complex, [PdCl2(C21H20N2)], contains a PdII atom in a slightly distorted square-planar coordination environment defined by two N atoms from one 2,4,6-trimethyl-N-[phen­yl(2-pyrid­yl)methyl­idene]aniline ligand and two Cl atoms, forming a five-membered ring (N—Pd—N—C—C). PMID:21579287

  18. Crystal structure of (2R*,3aR*)-2-phenyl-sulfonyl-2,3,3a,4,5,6-hexa-hydro-pyrrolo-[1,2-b]isoxazole.

    PubMed

    Hernández, Yaiza; Marcos, Isidro; Garrido, Narciso M; Sanz, Francisca; Diez, David

    2017-01-01

    The title compound, C12H15NO3S, was prepared by 1,3-dipolar cyclo-addition of 3,4-di-hydro-2H-pyrrole 1-oxide and phenyl vinyl sulfone. In the mol-ecule, both fused five-membered rings display a twisted conformation. In the crystal, C-H⋯O hydrogen bonds link neighbouring mol-ecules, forming chains running parallel to the b axis.

  19. Crystal structure of (2R*,3aR*)-2-phenyl­sulfonyl-2,3,3a,4,5,6-hexa­hydro­pyrrolo­[1,2-b]isoxazole

    PubMed Central

    Hernández, Yaiza; Marcos, Isidro; Garrido, Narciso M.; Sanz, Francisca; Diez, David

    2017-01-01

    The title compound, C12H15NO3S, was prepared by 1,3-dipolar cyclo­addition of 3,4-di­hydro-2H-pyrrole 1-oxide and phenyl vinyl sulfone. In the mol­ecule, both fused five-membered rings display a twisted conformation. In the crystal, C—H⋯O hydrogen bonds link neighbouring mol­ecules, forming chains running parallel to the b axis. PMID:28083143

  20. Astronaut Newman on flight deck

    NASA Image and Video Library

    1995-09-25

    STS069-378-027 (7-18 September 1995) --- Astronaut James H. Newman, mission specialist, turns 180 degrees to pose for a photograph at his busy workstation on the middeck of the Earth-orbiting Space Shuttle Endeavour. The Endeavour, with a five-member crew, launched on September 7, 1995, from the Kennedy Space Center (KSC). The multifaceted mission ended September 18, 1995, with a successful landing on Runway 33 at KSC.

  1. STS-69 crew on flight deck during Wake Shield retrieval

    NASA Image and Video Library

    1995-09-22

    STS069-355-023 (7-18 September 1995) --- Astronauts David M. Walker (right), mission commander, and Michael L. Gernhardt, mission specialist, busy themselves on Space Shuttle Endeavour’s flight deck during rendezvous operations involving one of two temporarily free-flying craft. Endeavour, with a five-member crew, launched on September 7, 1995, from the Kennedy Space Center (KSC). The multifaceted mission ended September 18, 1995, with a successful landing on Runway 33 at KSC.

  2. CMIX-04

    NASA Image and Video Library

    1995-09-25

    STS069-377-021 (7-18 September 1995) --- Astronaut Michael L. Gernhardt, mission specialist, works with a test called the Commercial Material Dispersion Apparatus Instrumentation Technology Associates, Inc., Experiment (CMIX) 04. The experiment is in one of the stowage lockers on Space Shuttle Endeavour’s middeck. Endeavour, with a five-member crew, launched on September 7, 1995, from the Kennedy Space Center (KSC). The mission ended September 18, 1995, with a successful landing on Runway 33 at KSC.

  3. NFAT Gene Family in Inflammation and Cancer

    PubMed Central

    Pan, M.-G.; Xiong, Y.; Chen, F.

    2013-01-01

    Calcineurin-NFAT signaling is critical for numerous aspects of vertebrate function during and after embryonic development. Initially discovered in T cells, the NFAT gene family, consisting of five members, regulates immune system, inflammatory response, angiogenesis, cardiac valve formation, myocardial development, axonal guidance, skeletal muscle development, bone homeostasis, development and metastasis of cancer, and many other biological processes. In this review we will focus on the NFAT literature relevant to the two closely related pathological systems: inflammation and cancer. PMID:22950383

  4. CDR Shepherd and CDR Cockrell in SM

    NASA Image and Video Library

    2001-02-09

    STS98-E-5062 (9 February 2001) --- The shuttle and station commanders are pictured at the "kitchen" table onboard the International Space Station in this digital still camera's view, recorded not long after the two crews reunited aboard the outpost. Astronaut William M. (Bill) Shepherd (left) is Expedition One commander and astronaut Kenneth D. Cockrell serves as mission commander for the five-member STS-98 crew.

  5. Synthetic and Biological Aspects of Thiadiazoles and their Condensed Derivatives: An Overview.

    PubMed

    Dwivedi, Jaya; Kaur, Navjeet; Kishore, D; Kumari, Simpal; Sharma, Swapnil

    2016-01-01

    The three heteroatoms containing five membered heterocycles such as thiadiazoles have been extensively studied due to their important pharmacological activities. The thiadiazole nucleus is an important class of compounds for new drug development. The chemical and biological behavior and synthesis of thiadiazole derivatives have gained much importance in last few decades. This review article provides up to date information about exploration of new methods, developments, synthetic strategies, and their diverse pharmaceutical activities.

  6. Expedient Access to 2,3-Dihydropyridines from Unsaturated Oximes by Rh(III)-Catalyzed C-H Activation.

    PubMed

    Romanov-Michailidis, Fedor; Sedillo, Kassandra F; Neely, Jamie M; Rovis, Tomislav

    2015-07-22

    α,β-Unsaturated oxime pivalates are proposed to undergo reversible C(sp(2))-H insertion with cationic Rh(III) complexes to furnish five-membered metallacycles. In the presence of 1,1-disubstituted olefins, these species participate in irreversible migratory insertion to give, after reductive elimination, 2,3-dihydropyridine products in good yields. Catalytic hydrogenation can then be used to convert these molecules into piperidines, which are important structural components of numerous pharmaceuticals.

  7. Theoretical Analysis of Kinetic Isotope Effects on Proton Transfer Reactions between Substituted α-Methoxystyrenes and Substituted Acetic Acids

    PubMed Central

    Wong, Kin Yiu; Richard, John P.; Gao, Jiali

    2009-01-01

    Primary kinetic isotope effects (KIEs) on a series of carboxylic acid-catalyzed protonation reactions of aryl-substituted α-methoxystyrenes (X-1) to form oxocarbenium ions have been computed using the Kleinert variational second-order perturbation theory (KP2) in the framework of Feynman path integrals (PI) along with the potential energy surface obtained at the B3LYP/6-31+G(d,p) level. Good agreement with the experimental data was obtained, demonstrating that this novel computational approach for computing KIEs of organic reactions is a viable alternative to the traditional method employing Bigeleisen equation and harmonic vibrational frequencies. Although tunneling makes relative small contributions to the lowering of the free energy barriers for the carboxylic acid catalyzed protonation reaction, it is necessary to include tunneling contributions to obtain quantitative estimates of the KIEs. Consideration of anharmonicity can further improve the calculated KIEs for the protonation of substituted α-methoxystyrenes by chloroacetic acid, but for the reactions of the parent and 4-NO2 substituted α-methoxystyrene with substituted carboxylic acids, the correction of anharmonicity overestimates the computed KIEs for strong acid catalysts. In agreement with experimental findings, the largest KIEs are found in nearly ergoneutral reactions, ΔGo ≈ 0, where the transition structures are nearly symmetric and the reaction barriers are relatively low. Furthermore, the optimized transition structures are strongly dependent on the free energy for the formation of the carbocation intermediate, i.e., the driving force ΔGo, along with a good correlation of Hammond shift in the transition state structure. PMID:19754046

  8. Theoretical analysis of kinetic isotope effects on proton transfer reactions between substituted alpha-methoxystyrenes and substituted acetic acids.

    PubMed

    Wong, Kin-Yiu; Richard, John P; Gao, Jiali

    2009-10-07

    Primary kinetic isotope effects (KIEs) on a series of carboxylic acid-catalyzed protonation reactions of aryl-substituted alpha-methoxystyrenes (X-1) to form oxocarbenium ions have been computed using the second-order Kleinert variational perturbation theory (KP2) in the framework of Feynman path integrals (PI) along with the potential energy surface obtained at the B3LYP/6-31+G(d,p) level. Good agreement with the experimental data was obtained, demonstrating that this novel computational approach for computing KIEs of organic reactions is a viable alternative to the traditional method employing Bigeleisen equation and harmonic vibrational frequencies. Although tunneling makes relatively small contributions to the lowering of the free energy barriers for the carboxylic acid catalyzed protonation reaction, it is necessary to include tunneling contributions to obtain quantitative estimates of the KIEs. Consideration of anharmonicity can further improve the calculated KIEs for the protonation of substituted alpha-methoxystyrenes by chloroacetic acid, but for the reactions of the parent and 4-NO(2) substituted alpha-methoxystyrene with substituted carboxylic acids, the correction of anharmonicity overestimates the computed KIEs for strong acid catalysts. In agreement with experimental findings, the largest KIEs are found in nearly ergoneutral reactions, DeltaG(o) approximately 0, where the transition structures are nearly symmetric and the reaction barriers are relatively low. Furthermore, the optimized transition structures are strongly dependent on the free energy for the formation of the carbocation intermediate, that is, the driving force DeltaG(o), along with a good correlation of Hammond shift in the transition state structure.

  9. In silico analysis of interaction pattern switching in ligandreceptor binding in Golgi α-mannosidase II induced by the protonated states of inhibitors.

    PubMed

    Sladek, V; Kóňa, J; Tokiwa, H

    2017-05-21

    Golgi α-mannosidase II (GM) is a pharmaceutical target for the design of inhibitors with anticancer activity. The known potent GM inhibitors undergo complex interactions with Zn(2+) ions and the active-site amino acids, many of which contain ionisable functional groups. Herein, the physical insight into the ligandreceptor interactions has been provided based on energy decomposition techniques: SAPT (symmetry adapted perturbation theory) and FMO-PIEDA (fragment molecular orbital-pair interaction energy decomposition analysis) for a large GM active-site cluster. Protonation-dependent molecular recognition in Golgi α-mannosidase was demonstrated for five inhibitors, mannose, and its transition state. Zn(2+) ion and Asp472 induce the key interactions with the deprotonated inhibitors (bearing an amino group in the neutral state), followed by Asp92 and Asp341. This interaction pattern is consistent for all the studied inhibitors and is similar to the interaction pattern of the enzyme native substrate - mannose. The interactions with Zn(2+) ion become repulsive for the protonated states of the inhibitors (bearing an amino group with +1 charge) and the mannosyl transition state. The importance of Asp92 and Asp204 considerably increases, while the interactions with Asp472 and Asp341 are slightly modified. The interaction pattern for the protonated ligands seems to have an oxocarbenium transition state-like character, rather than a Michaelis complex of GM. The electrostatic interactions with amino acids coordinating zinc ion are of key importance for both the neutral and protonated states of the inhibitors. The ligand's diol group has a dual role as an electron donor, coordinating zinc ion, and as an electron acceptor, interacting with Asp92 and Asp472 via strong hydrogen bonds. This interaction pattern is an essential structural feature of the potent GM inhibitors, which is consistent with the experimental findings. Based on the calculations, either the protonated or

  10. Is aspartate 52 essential for catalysis by chicken egg white lysozyme? The role of natural substrate-assisted hydrolysis

    SciTech Connect

    Matsumura, Ichiro; Kirsch, J.F.

    1996-02-13

    The chicken and goose egg white lysozymes (ChEWL and GoEWL) are homologues, but differ in substrate specificity. ChEWL catalyzes the hydrolysis of the glycosidic bonds of bacterial peptidoglycans and chitin-derived substrates, while GoEWL is specific for bacterial peptidoglycans. The active-site aspartate 52 residue of ChEWL, which is postulated to stabilize the oxocarbenium ion intermediate, has no counterpart in GoEWL. The substrate specificity of the D52A ChEWL mutant was compared with those of wild-type ChEWL and GoEWL. D52A ChEWL retains approximately 4% of the wild-type catalytic activity in reactions with three different bacterial cell suspensions. Asp52 therefore is not essential to the catalytic mechanism, accounting for only a 2 kcal/mol decrease in AG. The function of Asp52 in D52A ChEWL- and GoEWL-catalyzed cleavage of (carboxymethyl)chitin may be partially fulfilled by an appropriately positioned carboxyl group on the substrate (substrate-assisted catalysis). D52A ChEWL and GoEWL, unlike wild-type ChEWL, exhibit biphasic kinetics in the clearing of Micrococcus luteus cell suspensions, suggesting preferences for subsets of the linkages in the M. luteus peptidoglycan. These subsets do not exist in the peptidoglycans of Escherichia coli or Sarcina lutea, since neither D52A ChEWL nor GoEWL exhibits initial bursts in reactions with suspensions of these bacteria. We propose that substrate-assisted catalysis occurs in reactions of D52A ChEWL and GoEWL with M. luteus peptidoglycans, with the glycine carboxyl group of uncross-linked peptides attached to N-acetylmuramic acid partially substituting the function of the missing Asp52. 52 refs., 6 figs., 1 tab.

  11. Structure of Salmonella typhimurium OMP synthase in a complete substrates complex

    PubMed Central

    Grubmeyer, Charles; Hansen, Michael Riis; Fedorov, Alexander A.; Almo, Steven C.

    2012-01-01

    Dimeric Salmonella typhimurium orotate phosphoribosyltransferase (OMP synthase, E.C. 2.4.2.10), a key enzyme in de novo pyrimidine nucleotide synthesis, has been co-crystallized in a complete substrate complex of E•MgPRPP•orotate, and the structure solved to 2.2 Å resolution. This structure resembles that for Saccharomyces cerevisiae OMP synthase in showing a dramatic and asymmetric reorganization around the active site-bound ligands, but shares the same basic topology previously observed in complexes of OMP synthase from S. typhimurium and Escherichia coli. The catalytic loop (residues 99–109) contributed by subunit A is reorganized to close the active site situated in subunit B and to sequester it from solvent. Furthermore, the overall structure of subunit B is more compact, due to movements of the amino-terminal hood and elements of the core domain. The catalytic loop of subunit B remains open and disordered, and subunit A retains the more relaxed conformation observed in loop-open S. typhimurium OMP synthase structures. A non-proline cis-peptide formed between Ala71 and Tyr72 is seen in both subunits. The loop-closed catalytic site of subunit B reveals that both the loop and the hood interact directly with the bound pyrophosphate group of PRPP. In contrast to dimagnesium hypoxanthine-guanine phosphoribosyltransferases, OMP synthase contains a single catalytic Mg2+ in the closed active site. The remaining pyrophosphate charges of PRPP are neutralized by interactions with Arg99A, Lys100B, Lys103A, and His105A. The new structure confirms the importance of loop movement in catalysis by OMP synthase, and identifies several additional movements that must be accomplished in each catalytic cycle. A catalytic mechanism based on enzymic and substratea-ssisted stabilization of the previously documented oxocarbenium transition state structure is proposed. PMID:22531064

  12. Computational insights into active site shaping for substrate specificity and reaction regioselectivity in the EXTL2 retaining glycosyltransferase.

    PubMed

    Mendoza, Fernanda; Lluch, José M; Masgrau, Laura

    2017-09-14

    Glycosyltransferases are enzymes that catalyze a monosaccharide transfer reaction from a donor to an acceptor substrate with the synthesis of a new glycosidic bond. They are highly substrate specific and regioselective, even though the acceptor substrate often presents multiple reactive groups. Currently, many efforts are dedicated to the development of biocatalysts for glycan synthesis and, therefore, a better understanding of how natural enzymes achieve this goal can be of valuable help. To gain a deeper insight into the catalytic strategies used by retaining glycosyltransferases, the wild type EXTL2 (CAZy family GT64) and four mutant forms (at positions 293 and 246) were studied using QM(DFT)/MM calculations and molecular dynamics simulations. Existing hypotheses on the roles of Arg293, an enigmatic residue in the CAZy family GT64 that seemed to contradict a mechanism through an oxocarbenium intermediate, and of Asp246 have been tested. We also provide a molecular interpretation for the results of site-directed mutagenesis experiments. Moreover, we have investigated why an Asp, and not a Glu like in the family GT6, is found on the β-face of the transferred GlcNAc. It is predicted that an Asp246Glu mutant of EXTL2 would be unable to catalyze the α-1,4 transfer. The results herein presented clarify the roles that Arg293, Asp246 and Leu213 have at different stages of the catalytic process (for binding but also for efficient chemical reaction). Altogether, we provide a molecular view that connects the identity and conformation of these residues to the substrate specificity and regioselectivity of the enzyme, illustrating a delicate interplay between all these aspects.

  13. Hydrosilation of Carbonyl-Containing Substrates Catalyzed by an Electrophilic η1-Silane Iridium(III) Complex

    PubMed Central

    Park, Sehoon; Brookhart, Maurice

    2010-01-01

    Hydrosilation of a variety of ketones and aldehydes using the cationic iridium catalyst, (POCOP)Ir(H)(acetone)+, 1, (POCOP = 2,6-bis(di-tert-butyl phosphinito)phenyl) is reported. With triethyl silane, all but exceptionally bulky ketones undergo quantitative reactions employing 0.5 mol% catalyst in 20-30 min at 25 °C. Hydrosilation of esters and amides results in over-reduction and cleavage of C-O and C-N bonds, respectively. The diastereoselectivity of hydrosilation of 4-tert-butyl cyclohexanone has been examined using numerous silanes and is highly temperature dependent. Using EtMe2SiH, analysis of the ratio of cis:trans hydrosilation products as a function of temperature yields values for ΔΔH‡ (ΔH‡ (trans) - ΔH‡ (cis)) and ΔΔS‡ (ΔS‡ (trans) - ΔS‡(cis)) of -2.5 kcal/mol and -6.9 e.u., respectively. Mechanistic studies show that the ketone complex, (POCOP)Ir(H)(ketone)+, is the catalyst resting state and is in equilibrium with low concentration of the silane complex, (POCOP)Ir(H)(HSiR3)+. The silane complex transfers R3Si+ to ketone forming the oxocarbenium ion, R3SiOCR’2+, which is reduced by the resulting neutral dihydride 3, (POCOP)Ir(H)2, to yield product R3SiOCHR’2 and (POCOP)IrH+ which closes the catalytic cycle. PMID:21572562

  14. Stepwise Catalytic Mechanism via Short-Lived Intermediate Inferred from Combined QM/MM MERP and PES Calculations on Retaining Glycosyltransferase ppGalNAcT2

    PubMed Central

    Trnka, Tomáš; Kozmon, Stanislav; Tvaroška, Igor; Koča, Jaroslav

    2015-01-01

    The glycosylation of cell surface proteins plays a crucial role in a multitude of biological processes, such as cell adhesion and recognition. To understand the process of protein glycosylation, the reaction mechanisms of the participating enzymes need to be known. However, the reaction mechanism of retaining glycosyltransferases has not yet been sufficiently explained. Here we investigated the catalytic mechanism of human isoform 2 of the retaining glycosyltransferase polypeptide UDP-GalNAc transferase by coupling two different QM/MM-based approaches, namely a potential energy surface scan in two distance difference dimensions and a minimum energy reaction path optimisation using the Nudged Elastic Band method. Potential energy scan studies often suffer from inadequate sampling of reactive processes due to a predefined scan coordinate system. At the same time, path optimisation methods enable the sampling of a virtually unlimited number of dimensions, but their results cannot be unambiguously interpreted without knowledge of the potential energy surface. By combining these methods, we have been able to eliminate the most significant sources of potential errors inherent to each of these approaches. The structural model is based on the crystal structure of human isoform 2. In the QM/MM method, the QM region consists of 275 atoms, the remaining 5776 atoms were in the MM region. We found that ppGalNAcT2 catalyzes a same-face nucleophilic substitution with internal return (SNi). The optimized transition state for the reaction is 13.8 kcal/mol higher in energy than the reactant while the energy of the product complex is 6.7 kcal/mol lower. During the process of nucleophilic attack, a proton is synchronously transferred to the leaving phosphate. The presence of a short-lived metastable oxocarbenium intermediate is likely, as indicated by the reaction energy profiles obtained using high-level density functionals. PMID:25849117

  15. Transition State Analysis of the Arsenolytic Depyrimidination of Thymidine by Human Thymidine Phosphorylase†

    PubMed Central

    Schwartz, Phillip A.; Vetticatt, Mathew J.; Schramm, Vern L.

    2011-01-01

    Human thymidine phosphorylase (hTP) is responsible for thymidine (dT) homeostasis, promotes angiogenesis, and is involved in metabolic inactivation of antiproliferative agents that inhibit thymidylate synthase. Understanding its transition state structure is on the path to design transition state analogues. Arsenolysis of dT by hTP permits kinetic isotope effect (KIE) analysis of the reaction by forming thymine and the chemically unstable 2-deoxyribose 1-arsenate. The transition state for the arsenolytic reaction was characterized using multiple KIEs and computational analysis. Transition state analysis revealed a concerted bimolecular (ANDN) mechanism. A transition state constrained to match the intrinsic KIE values was found using density functional theory [B3LYP/6-31+G*]. An active site histidine is implicated as the catalytic base responsible for activation of the arsenate nucleophile and stabilization of the thymine leaving group during the isotopically sensitive step. At the transition state, the deoxyribose ring exhibits significant oxocarbenium ion character with bond-breaking (rC-N = 2.45 Å) nearly complete but no significant bond-making to the attacking nucleophile (rC-O = 2.95 Å). The transition state model predicts a deoxyribose conformation with a 2′-endo ring geometry. Transition state structure for the slow hydrolytic reaction of hTP involves a stepwise mechanism (Schwartz, P.A., Vetticatt, M.J., Schramm, V.L. (2010) J. Am. Chem. Soc. 132, 13425–13433), in contrast to the concerted mechanism described here for arsenolysis. PMID:21222488

  16. Distortional binding of transition state analogs to human purine nucleoside phosphorylase probed by magic angle spinning solid-state NMR

    PubMed Central

    Vetticatt, Mathew J.; Itin, Boris; Evans, Gary B.; Schramm, Vern L.

    2013-01-01

    Transition state analogs mimic the geometry and electronics of the transition state of enzymatic reactions. These molecules bind to the active site of the enzyme much tighter than substrate and are powerful noncovalent inhibitors. Immucillin-H (ImmH) and 4′-deaza-1′-aza-2′-deoxy-9-methylene Immucillin-H (DADMe-ImmH) are picomolar inhibitors of human purine nucleoside phosphorylase (hPNP). Although both molecules are electronically similar to the oxocarbenium-like dissociative hPNP transition state, DADMe-ImmH is more potent than ImmH. DADMe-ImmH captures more of the transition state binding energy by virtue of being a closer geometric match to the hPNP transition state than ImmH. A consequence of these similarities is that the active site of hPNP exerts greater distortional forces on ImmH than on DADMe-ImmH to “achieve” the hPNP transition state geometry. By using magic angle spinning solid-state NMR to investigate stable isotope-labeled ImmH and DADMe-ImmH, we have explored the difference in distortional binding of these two inhibitors to hPNP. High-precision determinations of internuclear distances from NMR recoupling techniques, rotational echo double resonance, and rotational resonance, have provided unprecedented atomistic insight into the geometric changes that occur upon binding of transition state analogs. We conclude that hPNP stabilizes conformations of these chemically distinct analogs having distances between the cation and leaving groups resembling those of the known transition state. PMID:24043827

  17. Theoretical Insights into the Reaction and Inhibition Mechanism of Metal-Independent Retaining Glycosyltransferase Responsible for Mycothiol Biosynthesis.

    PubMed

    Blanco Capurro, Juan I; Hopkins, Chad W; Pierdominici Sottile, Gustavo; González Lebrero, Mariano C; Roitberg, Adrian E; Marti, Marcelo A

    2017-01-26

    Understanding enzymatic reactions with atomic resolution has proven in recent years to be of tremendous interest for biochemical research, and thus, the use of QM/MM methods for the study of reaction mechanisms is experiencing a continuous growth. Glycosyltransferases (GTs) catalyze the formation of glycosidic bonds, and are important for many biotechnological purposes, including drug targeting. Their reaction product may result with only one of the two possible stereochemical outcomes for the reacting anomeric center, and therefore, they are classified as either inverting or retaining GTs. While the inverting GT reaction mechanism has been widely studied, the retaining GT mechanism has always been controversial and several questions remain open to this day. In this work, we take advantage of our recent GPU implementation of a pure QM(DFT-PBE)/MM approach to explore the reaction and inhibition mechanism of MshA, a key retaining GT responsible for the first step of mycothiol biosynthesis, a low weight thiol compound found in pathogens like Mycobacterium tuberculosis that is essential for its survival under oxidative stress conditions. Our results show that the reaction proceeds via a front-side SNi-like concerted reaction mechanism (DNAN in IUPAC nomenclature) and has a 17.5 kcal/mol free energy barrier, which is in remarkable agreement with experimental data. Detailed analysis shows that the key reaction step is the diphosphate leaving group dissociation, leading to an oxocarbenium-ion-like transition state. In contrast, fluorinated substrate analogues increase the reaction barrier significantly, rendering the enzyme effectively inactive. Detailed analysis of the electronic structure along the reaction suggests that this particular inhibition mechanism is associated with fluorine's high electronegative nature, which hinders phosphate release and proper stabilization of the transition state.

  18. The mechanism of the glycosylase reaction with hOGG1 base-excision repair enzyme: concerted effect of Lys249 and Asp268 during excision of 8-oxoguanine

    PubMed Central

    Šebera, Jakub; Hattori, Yoshikazu; Sato, Daichi; Řeha, David; Nencka, Radim; Kohno, Takashi

    2017-01-01

    Abstract The excision of 8-oxoguanine (oxoG) by the human 8-oxoguanine DNA glycosylase 1 (hOGG1) base-excision repair enzyme was studied by using the QM/MM (M06-2X/6-31G(d,p):OPLS2005) calculation method and nuclear magnetic resonance (NMR) spectroscopy. The calculated glycosylase reaction included excision of the oxoG base, formation of Lys249-ribose enzyme–substrate covalent adduct and formation of a Schiff base. The formation of a Schiff base with ΔG# = 17.7 kcal/mol was the rate-limiting step of the reaction. The excision of the oxoG base with ΔG# = 16.1 kcal/mol proceeded via substitution of the C1΄-N9 N-glycosidic bond with an H-N9 bond where the negative charge on the oxoG base and the positive charge on the ribose were compensated in a concerted manner by NH3+(Lys249) and CO2−(Asp268), respectively. The effect of Asp268 on the oxoG excision was demonstrated with 1H NMR for WT hOGG1 and the hOGG1(D268N) mutant: the excision of oxoG was notably suppressed when Asp268 was mutated to Asn. The loss of the base-excision function was rationalized with QM/MM calculations and Asp268 was confirmed as the electrostatic stabilizer of ribose oxocarbenium through the initial base-excision step of DNA repair. The NMR experiments and QM/MM calculations consistently illustrated the base-excision reaction operated by hOGG1. PMID:28334993

  19. Tuning the stereoelectronic properties of 1-sulfanylhex-1-enitols for the sequential stereoselective synthesis of 2-deoxy-2-iodo-β-D-allopyranosides.

    PubMed

    Kövér, Andrea; Boutureira, Omar; Matheu, M Isabel; Díaz, Yolanda; Castillón, Sergio

    2014-04-04

    The preparation of challenging 2-deoxy-2-iodo-β-D-allo precursors of 2-deoxy-β-D-ribo-hexopyranosyl units and other analogues is reported using a robust olefination-cyclization-glycosylation sequence. Here, we particularly focus on tuning the stereoelectronic properties of the alkenyl sulfides intermediates in order to improve the diastereoselectivity of the cyclization step and, hence, the efficiency of the overall transformation. Phosphine oxides with the general formula Ph2P(O)CH2SR (R = t-Bu, Cy, p-MeOPh, 2,6-di-ClPh, and 2,6-di-MePh) were easily synthesized and subsequently used in the olefination reaction with 2,3,5-tri-O-benzyl-D-ribose and -D-arabinose. The corresponding sugar-derived alkenyl sulfides were submitted to a 6-endo [I(+)]-induced cyclization, and the resulting 2-deoxy-2-iodohexopyranosyl-1-thioglycosides were used as glycosyl donors for the stereoselective synthesis of 2-deoxy-2-iodohexopyranosyl glycosides. Among the different S-groups studied, t-Bu derivative was the best performer for the synthesis of cholesteryl 2-deoxy-2-iodomannopyranosides, whereas for the synthesis of 2-deoxy-2-iodoallopyranosides none of the derivatives here studied proved superior to the phenyl analogue previously described. Glycosylation of cholesterol with different d-allo and d-manno derivatives produced 2-deoxy-2-iodoglycosides with stereoselectivities in the same order in each case, reinforcing the involvement of an oxocarbenium ion as the common intermediate of this crucial glycosylation step.

  20. Structural basis for nicotinamide cleavage and ADP-ribose transfer by NAD(+)-dependent Sir2 histone/protein deacetylases.

    PubMed

    Zhao, Kehao; Harshaw, Robyn; Chai, Xiaomei; Marmorstein, Ronen

    2004-06-08

    Sir2 enzymes are broadly conserved from bacteria to humans and have been implicated to play roles in gene silencing, DNA repair, genome stability, longevity, metabolism, and cell physiology. These enzymes bind NAD(+) and acetyllysine within protein targets and generate lysine, 2'-O-acetyl-ADP-ribose, and nicotinamide products. To provide structural insights into the chemistry catalyzed by Sir2 proteins we report the high-resolution ternary structure of yeast Hst2 (homologue of Sir two 2) with an acetyllysine histone H4 peptide and a nonhydrolyzable NAD(+) analogue, carba-NAD(+), as well as an analogous ternary complex with a reaction intermediate analog formed immediately after nicotinamide hydrolysis, ADP-ribose. The ternary complex with carba-NAD(+) reveals that the nicotinamide group makes stabilizing interactions within a binding pocket harboring conserved Sir2 residues. Moreover, an asparagine residue, N116, strictly conserved within Sir2 proteins and shown to be essential for nicotinamide exchange, is in position to stabilize the oxocarbenium intermediate that has been proposed to proceed the hydrolysis of nicotinamide. A comparison of this structure with the ADP-ribose ternary complex and a previously reported ternary complex with the 2'-O-acetyl-ADP-ribose reaction product reveals that the ribose ring of the cofactor and the highly conserved beta1-alpha2 loop of the protein undergo significant structural rearrangements to facilitate the ordered NAD(+) reactions of nicotinamide cleavage and ADP-ribose transfer to acetate. Together, these studies provide insights into the chemistry of NAD(+) cleavage and acetylation by Sir2 proteins and have implications for the design of Sir2-specific regulatory molecules.

  1. Crystal structures of Mycobacterium tuberculosis GlgE and complexes with non-covalent inhibitors

    SciTech Connect

    Lindenberger, Jared J.; Kumar Veleti, Sri; Wilson, Brittney N.; Sucheck, Steven J.; Ronning, Donald R.

    2015-08-06

    GlgE is a bacterial maltosyltransferase that catalyzes the elongation of a cytosolic, branched α-glucan. In Mycobacterium tuberculosis (M. tb), inactivation of GlgE (Mtb GlgE) results in the rapid death of the organism due to a toxic accumulation of the maltosyl donor, maltose-1-phosphate (M1P), suggesting that GlgE is an intriguing target for inhibitor design. In this study, the crystal structures of the Mtb GlgE in a binary complex with maltose and a ternary complex with maltose and a maltosyl-acceptor molecule, maltohexaose, were solved to 3.3 Å and 4.0 Å, respectively. The maltohexaose structure reveals a dominant site for α-glucan binding. To obtain more detailed interactions between first generation, non-covalent inhibitors and GlgE, a variant Streptomyces coelicolor GlgEI (Sco GlgEI-V279S) was made to better emulate the Mtb GlgE M1P binding site. The structure of Sco GlgEI-V279S complexed with α-maltose-C-phosphonate (MCP), a non-hydrolyzable substrate analogue, was solved to 1.9 Å resolution, and the structure of Sco GlgEI-V279S complexed with 2,5-dideoxy-3-O-α-D-glucopyranosyl-2,5-imino-D-mannitol (DDGIM), an oxocarbenium mimic, was solved to 2.5 Å resolution. These structures detail important interactions that contribute to the inhibitory activity of these compounds, and provide information on future designs that may be exploited to improve upon these first generation GlgE inhibitors.

  2. Glycosyltransfer in mutants of putative catalytic residue Glu303 of the human ABO(H) A and B blood group glycosyltransferases GTA and GTB proceeds through a labile active site.

    PubMed

    Blackler, Ryan J; Gagnon, Susannah M L; Polakowski, Robert; Rose, Natisha L; Zheng, Ruixiang B; Letts, James A; Johal, Asha R; Schuman, Brock; Borisova, Svetlana N; Palcic, Monica M; Evans, Stephen V

    2016-11-22

    The homologous glycosyltransferases α-1,3-N-acetylgalactosaminyltransferase (GTA) and α-1,3-galactosyltransferase (GTB) carry out the final synthetic step of the closely related human ABO(H) blood group A and B antigens. The catalytic mechanism of these model retaining enzymes remains under debate, where Glu303 has been suggested to act as a putative nucleophile in a double displacement mechanism, a local dipole stabilizing the intermediate in an orthogonal associative mechanism or a general base to stabilize the reactive oxocarbenium ion-like intermediate in an S N i-like mechanism. Kinetic analysis of GTA and GTB point mutants E303C, E303D, E303Q and E303A shows that despite the enzymes having nearly identical sequences, the corresponding mutants of GTA/GTB have up to a 13-fold difference in their residual activities relative to wild type. High-resolution single crystal X-ray diffraction studies reveal, surprisingly, that the mutated Cys, Asp and Gln functional groups are no more than 0.8 Å further from the anomeric carbon of donor substrate compared to wild type. However, complicating the analysis is the observation that Glu303 itself plays a critical role in maintaining the stability of a strained "double-turn" in the active site through several hydrogen bonds, and any mutation other than E303Q leads to significantly higher thermal motion or even disorder in the substrate recognition pockets. Thus, there is a remarkable juxtaposition of the mutants E303C and E303D, which retain significant activity despite disrupted active site architecture, with GTB/E303Q, which maintains active site architecture but exhibits zero activity. These findings indicate that nucleophilicity at position 303 is more catalytically valuable than active site stability and highlight the mechanistic elasticity of these enzymes.

  3. (4'-Acet-yloxy-1,3,1'-trioxo-1,3,4,4a,4b,5,6,7,9,9a-deca-hydro-spiro-[indene-2,9'-pyrano[4,3-a]pyrrolizin]-3'-yl)methyl acetate.

    PubMed

    Latha, N; Naga Siva Rao, J; Raghunathan, R; Divya, G; Lakshmi, S

    2013-11-13

    In the title compound, C23H23NO8, the dihedral angle between the five- and six-membered rings of the indene-dione moiety is 3.09 (13)°. The mean plane of the five-membered ring (which has a flat envelope conformation with the spiro C atom as the flap) is inclined to the mean plane of the central five-membered ring of the pyrrolizine unit by 76.48 (12)°. This central ring has a twist conformation on the N-C(spiro) bond. The outer ring of the pyrrolizine unit has an envelope conformation with the N atom as the flap. The mean planes of these two fused rings are inclined to one another by 65.28 (15)°. The pyran ring has a screw-boat conformation and its mean plane makes a dihedral angle of 29.50 (11)° with the mean plane of the central five-membered ring of the pyrrolizine unit. In the crystal, mol-ecules are linked via C-H⋯O hydrogen bonds, forming two-dimensional networks lying parallel to the ab plane.

  4. Switching behavior of carbon chains bridging graphene nanoribbons: effects of uniaxial strain.

    PubMed

    Akdim, Brahim; Pachter, Ruth

    2011-03-22

    Recently, several experiments demonstrated the stability of chain-like carbon nanowires bridged between graphene nanoribbons, paving the way for potential applications in nanodevices. On the basis of density functional tight-binding calculations, we demonstrated switching for chains terminated with a five-membered ring under an applied strain, serving as a model for morphological changes in realistic materials. Electron transport calculations showed an increase of up to 100% in the output current, achieved at a reverse bias voltage of -2 V and an applied strain of just 1.5%. Structural analysis suggested that the switching is driven by conformational changes, where in our case is triggered by the formation and annihilation of a five-membered ring at the interface of the chain-graphene edge. In addition, we showed that a five-membered ring can easily be formed at the interface under a source-drain bias or through a gate voltage. This mechanism can serve as an explanation of experimentally observed conductance for the materials.

  5. Shielding in and around Oxazole, Imidazole, and Thiazole: How Does the Second Heteroatom Affect Aromaticity and Bonding?

    PubMed

    Horner, Kate E; Karadakov, Peter B

    2015-07-17

    Isotropic magnetic shielding distributions in the regions of space surrounding oxazole, imidazole, and thiazole are used to investigate aromaticity and bonding in these five-membered heterocycles with two heteroatoms. This is achieved by constructing HF-GIAO and MP2-GIAO (Hartree-Fock and second-order Møller-Plesset perturbation theory with gauge-including atomic orbitals) isotropic shielding plots, within the 6-311++G(d,p) basis, using regular two-dimensional 0.05 Å grids in the molecular plane and in planes 0.5 and 1 Å above it. The extent of isotropic shielding delocalization in the contour plots in planes 1 Å above the molecular plane, which is a new sensitive two-dimensional aromaticity criterion, indicates that aromaticity decreases in the order thiazole > imidazole > oxazole; in combination with previous results on furan, pyrrole, and thiophene ( J. Org. Chem. 2013 , 78 , 8037 - 9043 ), the aromaticity ordering in the six five-membered heterocycles becomes thiophene > thiazole > pyrrole > imidazole > furan > oxazole. The results suggest that the inclusion of a second heteroatom in a five-membered heterocycle has a detrimental effect on its aromaticity, which is very minor in oxazole, when compared to furan, and small but noticeable in imidazole and pyrrole and in thiazole and thiophene.

  6. Regiodefined synthesis of brominated hydroxyanthraquinones related to proisocrinins

    PubMed Central

    Roy, Joyeeta; Mal, Tanushree; Jana, Supriti

    2016-01-01

    Summary Dibromobenzoisofuranone 12, synthesized in six steps, was regiospecifically annulated with 5-substituted cyclohexenones 13/36 in the presence of LiOt-Bu to give brominated anthraquinones 14/38 in good yields. Darzens condensation of 30 was shown to give chain-elongated anthraquinone 32. Alkaline hydrolysis of 38 furnished 39 representing desulfoproisocrinin F. PMID:27340445

  7. 2,5-disubstituted oxazole research: fluorescence quantum yields and laser conversion efficiencies of 2-(p-italic-biphenyl)-5-phenyl oxazole and its 5-p-italic-substituted derivatives

    SciTech Connect

    Yu Peifeng

    1986-03-01

    The fluorescence quantum yield and laser conversion efficiency of 2-(p-italic-biphenyl)-5-phenyl-oxazole and thirteen 5-substituted phenyl derivatives are measured. A brief discussion is also given on the relation between the subtituent effects and spectral properties of the compounds.

  8. Regioselective cross-coupling reactions of boronic acids with dihalo heterocycles.

    PubMed

    Houpis, Ioannis N; Liu, Renmao; Wu, Yanfei; Yuan, Yukuan; Wang, Youchu; Nettekoven, Ulrike

    2010-10-15

    The carboxylic acid anion moiety has been used as a tunable directing group in the cross-coupling reaction of 2,6-dichloronicotinic acid and 2,5-dibromo-1,2,4-triazole derivatives producing selectively the 2- or 6-substituted nicotinic acids, while only the 5-substituted triazoles were obtained under a variety of conditions.

  9. A polyoxometalate-organic supramolecular nanotube with high chemical stability and proton-conducting properties.

    PubMed

    Cao, Gao-Juan; Liu, Jing-Dong; Zhuang, Ting-Ting; Cai, Xiu-Hong; Zheng, Shou-Tian

    2015-02-07

    The use of 1H-1,2,4-triazole-3-thiol (H2trzS) has led to a rare inorganic-organic hybrid supramolecular nanotube built from novel Ni5-substituted polyoxotungstates, which presents interesting structural characteristics, high chemical stability, and proton-conducting properties.

  10. Quantitative autoradiographic mapping of focal herpes simplex virus encephalitis using a radiolabeled antiviral drug

    SciTech Connect

    Price, R.

    1984-12-18

    A method of mapping herpes simplex viral infection comprising administering a radiolabeled antiviral active 5-substituted 1-(2'-deoxy-2'-substituted-D-arabinofuranosyl) pyrimidine nucleoside to the infected subject, and scanning the area in which the infection is to be mapped for the radiolabel.

  11. Behavior of the potential antitumor V(IV)O complexes formed by flavonoid ligands. 1. Coordination modes and geometry in solution and at the physiological pH.

    PubMed

    Sanna, Daniele; Ugone, Valeria; Lubinu, Giuseppe; Micera, Giovanni; Garribba, Eugenio

    2014-11-01

    The coordination modes and geometry assumed in solution by the potent antitumor oxidovanadium(IV) complexes formed by different flavonoids were studied by spectroscopic (Electron Paramagnetic Resonance, EPR) and computational (Density Functional Theory, DFT) methods. A series of bidentate flavonoid ligands (L) with increasing structural complexity was examined, which can involve (CO, O(-)) donors and formation of five- and six-membered chelate rings, or (O(-), O(-)) donors and five-membered chelate rings. The geometry corresponding to these coordination modes can be penta-coordinated, [VOL2], or cis-octahedral, cis-[VOL2(H2O)]. The results show that, at physiological pH, ligands provided with (CO, O(-)) donor set yield cis-octahedral species with "maltol-like" coordination when five-membered chelate rings are formed (as with 3-hydroxyflavone), while penta-coordinated structures with "acetylacetone-like" coordination are preferred when the chelate rings are six-membered (as with chrysin). When both the binding modes are possible, as with morin, the "acetylacetone-like" coordination is observed. For the ligands containing a catecholic donor set, such as 7,8-dihydroxyflavone, baicalein, fisetin, quercetin and rutin, the formation of square pyramidal complexes with (O(-), O(-)) "catechol-like" coordination and five-membered chelate rings is preferred at physiological pH. The determination of the different coordination modes and geometry is important to define the biotransformation in the blood and the interaction of these complexes with the biological membranes. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. cine-Substitution reactions of metallabenzenes: an experimental and computational study.

    PubMed

    Wang, Tongdao; Zhang, Hong; Han, Feifei; Long, Lipeng; Lin, Zhenyang; Xia, Haiping

    2013-08-12

    Alkali-resistant osmabenzene [(SCN)2(PPh3)2Os{CHC(PPh3)CHCICH}] (2) can undergo nucleophilic aromatic substitution with MeOH or EtOH to give cine-substitution products [(SCN)2(PPh3)2Os{CHC(PPh3)CHCHCR}] (R=OMe (3), OEt(4)) in the presence of strong alkali. However, the reactions of compound 2 with various amines, such as n-butylamine and aniline, afford five-membered ring species, [(SCN)2(PPh3)2Os{CH=C(PPh3)CH=C(CH=NHR')}] (R'=nBu(8), Ph(9)), in addition to the desired cine-substitution products, [(SCN)2(PPh3)2Os{CHC(PPh3)CHCHC(NHR')}] (R'=nBu(6), Ph(7)), under similar reaction conditions. The mechanisms of these reactions have been investigated in detail with the aid of isotopic labeling experiments and density functional theory (DFT) calculations. The results reveal that the cine-substitution reactions occur through nucleophilic addition, dissociation of the leaving group, protonation, and deprotonation steps, which resemble the classical "addition-of-nucleophile, ring-opening, ring-closure" (ANRORC) mechanism. DFT calculations suggest that, in the reaction with MeOH, the formation of a five-membered metallacycle species is both kinetically and thermodynamically less favorable, which is consistent with the experimental results that only the cine-substitution product is observed. For the analogous reaction with n-butylamine, the pathway for the formation of the cine-substitution product is kinetically less favorable than the pathway for the formation of a five-membered ring species, but is much more thermodynamically favorable, again consistent with the experimental conversion of compound 8 into compound 6, which is observed in an in situ NMR experiment with an isolated pure sample of 8.

  13. Synthesis, quantitative structure-activity relationship and biological evaluation of 1,3,4-oxadiazole derivatives possessing diphenylamine moiety as potential anticancer agents.

    PubMed

    Abdel Rahman, Doaa Ezzat

    2013-01-01

    Synthesis of 2,5-disubstituted-1,3,4-oxadiazole (2a-c), 3-substituted aminomethyl-5-substituted-1,3,4-oxadiazole-2(3H)-thione (4a-m) and 2-substituted thio-5-substituted-1,3,4-oxadiazole (5a, b) had been described. All the synthesized derivatives were screened for anticancer activity against HT29 and MCF7 cancer cell lines using Sulfo-Rodamine B (SRB) standard method. Most of the tested compounds exploited potent antiproliferative activity against HT29 cancer cell line rather than MCF7 cancer cell line. Compounds 2a-c, 4f and 5a exhibited potent cytotoxicity (IC(50) 1.3-2.0 µM) and selectivity against HT29 cancer cell line. Quantitative structure-activity relationship (QSAR) study was applied to find a correlation between the experimental antiproliferative activities of the newly synthesized oxadiazole derivatives with their physicochemical parameter and topological index.

  14. The stereodynamics of 5,5'-disubstituted BIPHEPs.

    PubMed

    Maier, Frank; Trapp, Oliver

    2013-02-01

    We investigated the stereodynamics of 5,5'-substituted tropos BIPHEP ligands (2,2'-bis(diphenylphosphino)-biphenyls) by enantioselective dynamic high-performance liquid chromatography (DHPLC) to elucidate the influence of the substitution pattern and electronics of the substituents (methyl, methoxy, and hydroxyl groups). By temperature-dependent dynamic HPLC measurements the activation parameters ΔG(╪), ΔH(╪), and ΔS(╪) could be determined with high precision, revealing that the activation barrier of these 5,5'-substituted BIPHEP ligands ranges in a narrow band between 87.8 and 93.0 kJ mol(-1), making them highly attractive as deracemizable dynamic chiral ligands in asymmetric catalysis. Interestingly, the activation parameters are highly influenced by a hydroxyl or methoxy group in the 5,5'-position of the BIPHEP ligands. Copyright © 2012 Wiley Periodicals, Inc.

  15. Synthesis of α-d-glucosyl substituted methyl glycosides of 3-deoxy-α-d-manno- and d-glycero-α-d-talo-oct-2-ulosonic acid (Kdo/Ko) corresponding to inner core fragments of Acinetobacter lipopolysaccharide.

    PubMed

    Pokorny, Barbara; Müller-Loennies, Sven; Kosma, Paul

    2014-06-04

    The α-d-glucopyranosyl-(1→5)-substituted methyl glycosides of 3-deoxy-α-d-manno-oct-2-ulosonic acid (Kdo), 3-deoxy-α-d-lyxo-hept-2-ulosonic acid (Kdh), and d-glycero-α-d-talo-oct-2-ulosonic acid (Ko) were prepared using orthogonally protected glycosyl acceptor derivatives via glycosylation with a torsionally disarmed 4,6-O-benzylidene protected trifluoroacetimidate glucosyl donor followed by global deprotection. The related 6-O-phosphoryl-α-d-glucopyranosyl-(1→5)-substituted Kdo and Kdh derivatives were derived from a benzylidene-protected glucosyl intermediate using phosphoramidite and phosphoryl chloride-based phosphorylation steps, respectively. The deprotected disaccharides serve as ligands to study lectin binding of Acinetobacter lipopolysaccharide core oligosaccharides. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. (E)-5-[(2-Hy-droxy-3-meth-oxy-benzyl-idene)amino]-1,3,4-thia-diazole-2(3H)-thione.

    PubMed

    Kargar, Hadi; Kia, Reza

    2011-12-01

    In the title compound, C(10)H(9)N(3)O(2)S(2), the dihedral angle between the benzene ring and the five-membered ring is 1.54 (13)°. An intra-molecular O-H⋯N hydrogen bond makes an S(6) ring. In the crystal, mol-ecules are linked together through bifurcated N-H⋯(O,O) hydrogen bonds having R(1) (2)(5) ring motifs, forming chains along the b axis. The crystal structure also features π-π inter-actions, with centroid-centroid distances of 3.699 (3)-3.767 (3) Å.

  17. An Unexpected Deamination Reaction after Hydrolysis of the Pyrimidine (6-4) Pyrimidone Photoproduct

    PubMed Central

    2015-01-01

    Pyrimidine (6-4) pyrimidone photoproduct (6-4PP), a common DNA photolesion formed under solar irradiation, was indicated to hydrolyze under strong basic conditions, breaking the N3–C4 bond at the 5′-thymine. The reanalysis of this reaction revealed that the resulting water adduct may not be stable as previously proposed; it readily undergoes an esterification reaction induced by the 5-OH group at 6-4PP to form a five-membered ring, eliminating a molecule of ammonia. PMID:25250878

  18. A SWOT analysis of the organization and financing of the Danish health care system.

    PubMed

    Christiansen, Terkel

    2002-02-01

    The organization and financing of the Danish health care system was evaluated within a framework of a SWOT analysis (analysis of Strengths, Weaknesses, Opportunities and Threats) by a panel of five members with a background in health economics. The present paper describes the methods and materials used for the evaluation: selection of panel members, structure of the evaluation task according to the health care triangle model, selection of background material consisting of documents and literature on the Danish health care system, and a 1-week study visit.

  19. Summary of the SWOT panel's evaluation of the organisation and financing of the Danish health care system.

    PubMed

    Christiansen, Terkel

    2002-02-01

    The organisation and financing of the Danish health care system was evaluated within a framework of a SWOT analysis (analysis of strengths, weaknesses, opportunities and threats) by a panel of five members with a background in health economics. This paper systematically summarises the panel's assessments, within the framework of the triangular model of health care. The members of the panel are in agreement on a number of aspects, while their views on other aspects differ. In general they find many strength in the way the system is organised and financed more so in the primary sector than in the hospital sector.

  20. Noncovalent Substrate-Directed Enantioselective Heck Reactions: Synthesis of S- and P-Stereogenic Heterocycles.

    PubMed

    de Azambuja, Francisco; Carmona, Rafaela C; Chorro, Tomaz H D; Heerdt, Gabriel; Correia, Carlos Roque D

    2016-08-01

    S- and P-Stereogenic heterocycles were synthesized by a remarkably simple enantioselective Heck desymmetrization reaction based on the unprecedented noncovalent directing effect of S=O and P=O functionalities. Selected prochiral symmetric substrates were efficiently arylated using the recently disclosed chiral PyraBOx ligand under mild and open-flask reaction conditions. Several five-membered aryl- sulfones, sulfoxides, and phosphine oxides were synthesized in good to excellent yields, in good to high diastereoselectivity, and enantiomeric ratios up to 98:2. Theoretical calculations also support the noncovalent directing effect of the S=O and P=O functionalities during the arylation process.

  1. 3-Carb-oxy-methyl-1H-indole-4-carb-oxy-lic acid.

    PubMed

    Mao, Shulin

    2012-01-01

    In the title compound, C(11)H(9)NO(4), the carboxyl group bonded to the six-membered ring lies close to the plane of the 1H-indole ring system [dihedral angle = 13.13 (9)°], whereas the carb-oxy-lic acid group linked to the five-membered ring by a methyl-ene bridge is close to perpendicular [78.85 (9)°]. In the crystal, O-H⋯O and N-H⋯O hydrogen bonds link the mol-ecules, generating (110) sheets.

  2. 8-Bromo-3-(cyclo­propanylcarbon­yl)-5-methyl­indolizine-1-carbonitrile

    PubMed Central

    Fan, Dahe; Tang, Fan; Wang, Wei

    2012-01-01

    The asymmetric unit of the title compound, C14H11BrN2O, contains three independent mol­ecules with very similar geometries. The dihedral angles between the side chain of the cyclo­propyl plane and the five-membered ring to which it is attached are 55.0 (2), 58.1 (2) and 60.2 (3)° for the three mol­ecules. Each mol­ecule forms an intra­molecular C—H⋯O hydrogen bond. PMID:22719653

  3. Familial abnormalities of thyroxine binding proteins: some problems of recognition and interpretation.

    PubMed Central

    Neild, J E; Byfield, P G; Lalloz, M R; Tait, D; Marigold, J H; Croft, D N; Slavin, B M

    1985-01-01

    A three generation family study was carried out after inappropriate treatment with radioactive iodine of a 50 year old woman with a raised serum total thyroxine concentration and free thyroxine index. Subsequent investigations showed that she and five members of her family had raised thyroxine binding globulin concentrations. Free thyroxine and free triiodothyronine concentrations were normal. Problems encountered in the recognition of this thyroxine binding protein disorder are discussed. Clinicians and clinical biochemists should be aware of these pitfalls and thus avoid further incorrect treatment on the basis of biochemical findings, even though free hormone estimations are now becoming readily available. PMID:3919066

  4. Biodegradation and dissolution of polyaromatic hydrocarbons by Stenotrophomonas sp.

    PubMed

    Tiwari, Bhagyashree; Manickam, N; Kumari, Smita; Tiwari, Akhilesh

    2016-09-01

    The aim of this work was to study the biodegradation capabilities of a locally isolated bacterium, Stenotrophomonas sp. strain IITR87 to degrade the polycyclic aromatic hydrocarbons and also check the preferential biodegradation of polycyclic aromatic hydrocarbons (PAHs). From preferential substrate degradation studies, it was found that Stenotrophomonas sp. strain IITR87 first utilized phenanthrene (three membered ring), followed by pyrene (four membered ring), then benzo[α]pyrene (five membered ring). Dissolution study of PAHs with surfactants, rhamnolipid and tritonX-100 showed that the dissolution of PAHs increased in the presence of surfactants.

  5. Hydrogen-bonding between the hydrogen peroxide molecule and the hydroperoxy radical (H 2O 2-HO 2): the global minimum

    NASA Astrophysics Data System (ADS)

    Alikhani, Mohammad Esmaı̈l; Barone, Vincenzo

    2004-06-01

    Spectroscopic properties of H 2O 2-HO 2 have been re-investigated by post Hartree-Fock methods including anharmonic vibrational effects through a second order perturbative approach. The results have been compared to recent experimental data. The very low barrier height computed for the conversion of the five-membered complex into its more stable six-membered counterpart (27 cm -1) explains why only the six-membered hydrogen-bonded complex is observed in argon matrices. The calculated anharmonic frequencies of the latter complex are in excellent agreement with experimental data.

  6. The Antiaircraft Journal. Volume 97, Number 4, July-August 1954

    DTIC Science & Technology

    1954-08-01

    in the regiment. The basic unit of the Party, the cell of from three to five members, is found in each of the twelve companies in the regiment. The...chief of the cell is responsible for inducing the best of the non-party men to apply to join the Communist Party. Komsomol and Com- munist Party members...Government. Usually, soldiers are eager to join the Party cells since membership in them facilitates pro- motion. In fact, Party membership is a virtual

  7. H12461. Fluorine as a Regiocontrol Element in the Ring Openings of Bicyclic Aziridiniums

    PubMed Central

    Lam, Yu-hong; Cossy, Janine; Prado, Domingo Gomez; Cochi, Anne

    2013-01-01

    The origin of the variation in the regioselectivity of the nucleophilic ring-opening of a series of bicyclic aziridinium ions derived from N-alkylprolinols was investigated by quantum chemical computations (M06-2X/6-31+G(d,p)—SMD). These aziridiniums differ only in the degree and the stereochemistry of fluoro substitution at C(4). With the azide ion as nucleophile, the ratio of the piperidine to the pyrrolidine product was computed. An electrostatic gauche effect influences the conformation of the adjoining five-membered ring in the fluorinated bicyclic aziridinium. This controls the regioselectivity of the aziridinium ring-opening. PMID:23471532

  8. Diastereoselective rhodium-catalyzed ene-cycloisomerization reactions of alkenylidenecyclopropanes: total synthesis of (-)-α-kainic acid.

    PubMed

    Evans, P Andrew; Inglesby, Phillip A

    2012-02-29

    The rhodium-catalyzed ene-cycloisomerization of alkenylidenecyclopropanes provides an atom-economical approach to five-membered carbo- and heterocycles that contain two new stereogenic centers. A key and striking feature of this protocol is that the alkene geometry does not impact the efficiency and diastereocontrol, which provides excellent synthetic versatility. For instance, (E)- and (Z)-allylic alcohols furnish the corresponding aldehydes with similar efficiency and selectivity. This process facilitates the construction of a key intermediate in an eight-step total synthesis of (-)-α-kainic acid. © 2012 American Chemical Society

  9. 2,3-O-Isopropyl­idene-3-C-phenyl­erythrofuran­ose

    PubMed Central

    Robinson, Tony V.; Taylor, Dennis K.; Tiekink, Edward R. T.

    2009-01-01

    The title compound, C13H16O, comprises two fused five-membered rings. Each ring has an envelope conformation, with the ether O atom in the furan­ose ring, and the CMe2 atom in the acetonide ring as the flap atoms. In the crystal, centrosymmetrically related mol­ecules associate via hydr­oxy–ether O—H⋯O hydrogen bonds and the resulting dimers are linked into a supra­molecular chain with a flattened topology via C—H⋯Ohydr­oxy contacts, and aligned in the a-axis direction. PMID:21578852

  10. Crystal structure of 3,4′-diphenyl-3′-p-tolyl-4′H-spiro­[indan-2,5′-[1,2]oxazol]-1-one

    PubMed Central

    Mahfoud, Asmae; Al Houari, Ghali; El Yazidi, Mohamed; Saadi, Mohamed; El Ammari, Lahcen

    2015-01-01

    In the title compound, C30H23NO2, the five-membered rings are both in envelope conformations with the same spiro C atom as the flap. The benzene ring and the two phenyl rings are inclined to the mean plane of the indene ring system by 83.98 (8), 81.46 (8) and 72.31 (7)°. In the crystal, mol­ecules are linked by pairs of C—H⋯O hydrogen bonds into inversion dimers. The dimers are further connected by C—H⋯N inter­actions, forming layers parallel to (10-1). PMID:26594573

  11. Crystal structure of 3,4'-diphenyl-3'-p-tolyl-4'H-spiro-[indan-2,5'-[1,2]oxazol]-1-one.

    PubMed

    Mahfoud, Asmae; Al Houari, Ghali; El Yazidi, Mohamed; Saadi, Mohamed; El Ammari, Lahcen

    2015-11-01

    In the title compound, C30H23NO2, the five-membered rings are both in envelope conformations with the same spiro C atom as the flap. The benzene ring and the two phenyl rings are inclined to the mean plane of the indene ring system by 83.98 (8), 81.46 (8) and 72.31 (7)°. In the crystal, mol-ecules are linked by pairs of C-H⋯O hydrogen bonds into inversion dimers. The dimers are further connected by C-H⋯N inter-actions, forming layers parallel to (10-1).

  12. Crystal structure of 1,2,3,5-di-O-methyl­ene-α-d-xylo­furan­ose

    PubMed Central

    Tiritiris, Ioannis; Tussetschläger, Stefan; Kantlehner, Willi

    2015-01-01

    The title compound, C7H10O5, was synthesized by reaction of d-xylose with paraformaldehyde. In the crystal, the central part of the mol­ecule consists of a five-membered C4O ring with an envelope conformation, with the methine C atom adjacent to the O atom being the flap. The protected O atoms of both cyclic acetal groups are oriented so that the four chiral C atoms of the furan­ose part show an R configuration. C—H⋯O hydrogen bonds are present between adjacent mol­ecules, generating a three-dimensional network. PMID:26594582

  13. Methyl 2-[(3RS,4RS)-3-phenyl-4-(phenyl­sulfon­yl)isoxazolidin-2-yl]acetate

    PubMed Central

    Gültekin, Zeynep; Civan, Mehmet; Frey, Wolfgang; Hökelek, Tuncer

    2014-01-01

    In the title compound, C18H19NO5S, the five-membered isoxazolidine ring is in a half-chair conformation, and the phenyl rings are oriented at a dihedral angle of 66.53 (3)°. In the crystal, C—H⋯O hydrogen bonds link the mol­ecules into a three-dimensional supra­molecular structure. A weak C—H⋯π inter­action is also observed between adjacent mol­ecules. PMID:24940296

  14. The human growth hormone gene is regulated by a multicomponent locus control region

    SciTech Connect

    Jones, B.; Cooke, N.E.; Liebhaber, S.A.; Monks, B.R.

    1995-12-01

    This article describes research involving the five-member human growth hormone (hGH)/chorionic somatomammotropin (hCS) gene cluster and its expression in the placenta. The results indicate that interactions among multiple elements are required to restrict hGH transcription to the pituitary and generate appropriate levels of expression in the mouse genome. In addition, the results suggest a role for shared and unique regulatory sequences in locus control region-mediated expression of the hGH/hCS gene cluster in the pituitary and possibly the placenta. 67 refs., 9 figs.

  15. Further evidence for heredity of pterygium.

    PubMed

    Romano, Vito; Steger, Bernhard; Kovacova, Adriana; Kaye, Stephen B; Willoughby, Colin E

    2016-12-01

    Epidemiological reports strongly indicate that pterygium is an ophthalmoheliosis: a sun-related eye disease. Familial occurrence of pterygium is rare but supports the concept that heredity may predispose the conjunctiva to react abnormally to atmospheric-environmental stimuli. We describe a two generation Caucasian family of five members from the United Kingdom, four of whom developed pterygia in early adulthood with autosomal dominant inheritance. The present report confirms the significance of heredity in the pathogenesis of pterygium. Understanding the genetic basis of pterygium pathogenesis is clinically relevant, particularly in the management of patients who develop recurrent and aggressive pterygia at younger ages.

  16. 2-Ethyl-6,6-ethyl­enedisulfanediyl-7-methoxy­methyl-1,2,3,4,5,6-hexa­hydro-1,5-methano­azocino[4,3-b]indol-3-one

    PubMed Central

    Tercan, Barış; Şahin, Ertan; Patır, Süleyman; Hökelek, Tuncer

    2010-01-01

    The title compound, C20H24N2O2S2, consists of a tetra­cyclic ring system containing an azocino skeleton with ethyl, dithiol­ane and methoxy­methyl groups as substituents. The benzene and five-membered rings are nearly coplanar, with a dihedral angle of 2.78 (11)°. The dithiol­ane ring adopts an envelope conformation. In the crystal structure, inter­molecular C—H⋯O hydrogen bonds link the mol­ecules into chains nearly parallel to the c axis. Two C—H⋯π inter­actions are also present. PMID:21579758

  17. 6,6-[Ethyl­enebis(sulfanediyl)]-2-(2-methoxy­ethyl)-1,2,3,4,5,6-hexa­hydro-1,5-methano-1H-azocino[4,3-b]indol-3-one

    PubMed Central

    Tercan, Barış; Yüksel, Fatma; Patır, Süleyman; Hökelek, Tuncer

    2010-01-01

    The title compound, C19H22N2O2S2, consists of a tetra­cyclic ring system containing an azocine skeleton with methoxy­ethyl and dithiol­ane groups as substituents. The benzene and five-membered N-heterocyclic rings are nearly coplanar, making a dihedral angle of 0.81 (12)°. The dithiol­ane ring adopts an envelope conformation. Inter­molecular N—H⋯O hydrogen-bonding and weak C—H⋯π inter­actions are present in the crystal structure. PMID:21579376

  18. Instrumental analysis for differentiation of beers and evaluation of beer ageing

    NASA Astrophysics Data System (ADS)

    Dreve, Simina; Voica, Cezara; Dragan, Felicia; Georgiu, Monica

    2013-11-01

    A representative selection of 5 different beers commercially available were measured spectrophotometrically in UV-Vis spectral region and by fluorescence spectroscopy, in order to determine qualitative differentiation due to the mainly iso-R-acids (with a five member ring) originating from R-acids present in hops. Minerals and trace elements analysis were also performed by ICP-MS method. The determination of the bitter organic acids in beers and of the content in metallic ions can be used as indicators for differentiation of beers and evaluation of beer ageing.

  19. Liftoff of Space Shuttle Endeavour on mission STS-97

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Space Shuttle Endeavour rockets off Launch Pad 39B in a perfect, on-time launch. Liftoff of Endeavour occurred at 10:06:01 p.m. EST on mission STS-97. Endeavour and its five-member crew will deliver U.S. solar arrays to the International Space Station and be the first Shuttle crew to visit the Station'''s first resident crew. The 11-day mission includes three spacewalks. This marks the 101st mission in Space Shuttle history and the 25th night launch. Endeavour is expected to land Dec. 11 at 6:19 p.m. EST.

  20. Liftoff of Space Shuttle Endeavour on mission STS-97

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Twin columns of flame spew from the solid rocket boosters lifting Space Shuttle Endeavour out of the smoke and steam and into the night sky. Liftoff occurred on time at 10:06:01 p.m. EST. The Shuttle and its five-member crew will deliver U.S. solar arrays to the International Space Station and be the first Shuttle crew to visit the Station'''s first resident crew. The 11-day mission includes three spacewalks. This marks the 101st mission in Space Shuttle history and the 25th night launch. Endeavour is expected to land at KSC Dec. 11 at 6:19 p.m. EST.

  1. African RH needs addressed in new video production.

    PubMed

    1999-09-01

    The problems encountered in reproductive health (RH) and family planning in sub-Saharan Africa are met through a video production. A video film has been produced to create awareness of the issues among donor agencies, policy-makers and program managers/implementers. The video is also produced to promote partnership and collaboration between governmental and nongovernmental organizations to teach community-based RH approaches. A five-member video production team led by JOICFP senior program officer Atsuhi Yoshino, visited Tanzania, Zambia and Ghana to take pictures for the videos from June 10, 1999 through July 22, 1999. Specific activities from each country are cited to illustrate problems and solutions.

  2. 2-(4-Isopropyl­benzylidene)propanoic acid

    PubMed Central

    Muhammad, Niaz; Tahir, M. Nawaz; Ali, Saqib; Zia-ur-Rehman; Kashmiri, Muhammad Akram

    2008-01-01

    The two mol­ecules in the asymmetric unit of the title compound, C13H16O2, form dimers through O—H⋯O hydrogen bonding, resulting in R 2 2(8) rings. Each carboxyl­ O atom is involved in inter­amolecular C—H⋯O hydrogen bonds, forming five-membered rings. There exist dissimilar dihedral angles within the two mol­ecules, for example the carboxylate and isopropyl groups make dihedral angles of 59.6 (4) and 71.7 (3)° in the two molecules. There are no intermolecular π inter­actions. PMID:21203170

  3. Crystal structure of rac-3-hy­droxy-2-(p-tol­yl)-2,3,3a,4,7,7a-hexa­hydro-1H-4,7-methano­isoindol-1-one

    PubMed Central

    Aslantaş, Mehmet; Çelik, Cumali; Çelik, Ömer; Karayel, Arzu

    2015-01-01

    In the title compound, C16H17NO2, the cyclo­hexene ring adopts a boat conformation, and the five-membered rings have envelope conformations with the bridging atom as the flap. Their mean planes are oriented at a dihedral angle of 86.51 (7)°. The mol­ecular structure is stabilized by a short intra­molecular C—H⋯O contact. In the crystal, mol­ecules are linked by O—H⋯O hydrogen bonds forming chains propagating along [100]. The chains are linked by C—H⋯π inter­actions, forming slabs parallel to (001). PMID:25844217

  4. Metallic three-coordinated carbon networks with eight-membered rings showing high density of states at the Fermi level.

    PubMed

    Noda, Yusuke; Ono, Shota; Ohno, Kaoru

    2014-04-21

    Using a density functional method to study the electronic structure of various three-coordinated sp(2) carbon nanostructures, we find that the presence of an eight-membered ring adjoined to two five-membered rings in a unit cell brings about the simultaneous occurrence of flat and dispersive bands, quite similar to the band structure of precious metals. These bands are parts of an anisotropic Dirac cone tilted from an isotropic one. We reveal that in-phase and out-of-phase oscillations in the sign of the phase of the Kohn-Sham orbital contribute to the appearance of the unique band structures.

  5. Construction of a Chiral Silicon Center by Rhodium-Catalyzed Enantioselective Intramolecular Hydrosilylation.

    PubMed

    Naganawa, Yuki; Namba, Tomoya; Kawagishi, Mayu; Nishiyama, Hisao

    2015-06-22

    Rhodium-catalyzed enantioselective desymmetrizing intramolecular hydrosilylation of symmetrically disubstituted hydrosilanes is described. The original axially chiral phenanthroline ligand (S)-BinThro (Binol-derived phenanthroline) was found to work as an effective chiral catalyst for this transformation. A chiral silicon stereogenic center is one of the chiral motifs gaining much attention in asymmetric syntheses and the present protocol provides cyclic five-membered organosilanes incorporating chiral silicon centers with high enantioselectivities (up to 91 % ee). The putative active Rh(I) catalyst takes the form of an N,N,O-tridentate coordination complex, as determined by several complementary experiments.

  6. Crystal structure of 3a,6,6,9a-tetra­methyl­dodeca­hydro­naphtho­[2,1-b]furan-2-ol

    PubMed Central

    Shi, Xin-Wei; Li, Sheng-Kun; Li, Dang-Dang; Lu, Qiang-Qiang

    2015-01-01

    The title compound (common name: sclaral), C16H28O2, is a sclareolide derivative, which was synthesized from sclareolide itself. In the mol­ecule, the two six-membered rings, A and B, of the labdane skeleton adopt chair conformations and the five-membered O-containing heterocyclic ring C displays an envelope conformation, with the methine C atom of the fused C—C bond as the flap. In the crystal, mol­ecules are linked by O—H⋯O hydrogen bonds, forming chains propagating along [100]. PMID:26594436

  7. STS-32 Columbia, OV-102, liftoff from KSC LC Pad 39A is reflected in waterway

    NASA Image and Video Library

    1990-01-09

    STS032-S-069 (9 Jan. 1990) --- The space shuttle Columbia, with a five member crew aboard, lifts off for the ninth time as STS-32 begins a 10-day mission in Earth orbit. Leaving from Launch Pad 39A at 7:34:59:98 a.m. EST, in this horizontal (cropped 70mm) frame, Columbia is seen reflected in nearby marsh waters some 24 hours after dubious weather at the return-to-launch site (RTLS) had cancelled a scheduled launch. Onboard the spacecraft were astronauts Daniel C. Brandenstein, James D. Wetherbee, Bonnie J. Dunbar, G. David Low and Marsha S. Ivins. Photo credit: NASA

  8. Medicinal Chemistry Perspective of Fused Isoxazole Derivatives.

    PubMed

    Barmade, Mahesh A; Murumkar, Prashant R; Sharma, Mayank Kumar; Yadav, Mange Ram

    2016-01-01

    Nitrogen containing heterocyclic rings with an oxygen atom is considered as one of the best combination in medicinal chemistry due to their diversified biological activities. Isoxazole, a five membered heterocyclic azole ring is found in naturally occuring ibetonic acid along with some of the marketed drugs such as valdecoxib, flucloxacillin, cloxacillin, dicloxacillin, and danazol. It is also significant for showing antipsychotic activity in risperidone and anticonvulsant activity in zonisamide, the marketed drugs. This review article covers research articles reported till date covering biological activity along with SAR of fused isoxazole derivatives.

  9. N-(2-Carb-oxy-eth-yl)-2,5-dide-oxy-2,5-imino-d-mannonic acid [(3R,4R,5R)-1-(2-carb-oxy-eth-yl)-3,4-dihy-droxy-5-hy-droxy-methyl-l-proline].

    PubMed

    Edgeley, David S; Martínez, R Fernando; Jenkinson, Sarah F; Nash, Robert J; Fleet, George W J; Thompson, Amber L

    2012-10-01

    The absolute stereochemistry of the title compound, C(9)H(15)NO(7), was determined from the use of d-glucuronolactone as the starting material. The compound crystallizes as the zwitterion. The five-membered ring adopts an envelope conformation with the -CH(2)OH-substituted C atom forming the flap. An intramolecular N-H⋯O hydrogen-bond occurs. In the crystal, the compound exists as a three-dimensional O-H⋯O intermolecular hydrogen-bonded network with each mol-ecule acting as a donor and acceptor for four hydrogen bonds.

  10. Ethane-1,2-diyl bis­(pyridine-3-car­box­ylate)

    PubMed Central

    Brito, Iván; Vallejos, Javier; López-Rodríguez, Matías; Cárdenas, Alejandro

    2010-01-01

    The title compound, C14H12N2O4, has twofold imposed crystallographic symmetry in the solid state. The asymmetric unit contains one half-mol­ecule. An intra­molecular C—H⋯O hydrogen bond is formed between the carboxyl­ate O group and one H atom of the aromatic ring such that a five-membered ring is formed. The angle between the planes of symmetry-related aromatic rings is 44.71 (19)°. PMID:21580003

  11. Unsymmetrically Extended Polyfused Aromatics Embedding Coronene and Perylene Frameworks: Syntheses and Properties.

    PubMed

    Kumar, Sushil; Ho, Man-Tzu; Tao, Yu-Tai

    2016-01-15

    A series of polyfused aromatics containing coronene and perylene in their frameworks was successfully constructed by a modified Ramirez-Corey-Fuchs reaction as the key reaction. Typical six-membered annulation and atypical five-membered annulation through controlled reaction conditions led to a range of extensively conjugate aromatics as possible candidates for organic semiconductors. A significant p-type field-effect mobility of 0.42-0.64 cm(2)/V·s was obtained from one of the derivatives, dibenzo[a,d]coronene.

  12. Structure-activity relationships for pyrido-, imidazo-, pyrazolo-, pyrazino-, and pyrrolophenazinecarboxamides as topoisomerase-targeted anticancer agents.

    PubMed

    Gamage, Swarna A; Spicer, Julie A; Rewcastle, Gordon W; Milton, John; Sohal, Sukhjit; Dangerfield, Wendy; Mistry, Prakash; Vicker, Nigel; Charlton, Peter A; Denny, William A

    2002-01-31

    Heterocyclic phenazinecarboxamides were prepared by condensation of aminoheterocycles and 2-halo-3-nitrobenzoic acids, followed by reductive ring closure and amidation. They showed similar inhibition of paired cell lines that underexpressed topo II or overexpressed P-glycoprotein, indicating a non topo II mechanism of cytotoxicity and indifference to P-glycoprotein mediated multidrug resistance. Compounds with a fused five-membered heterocyclic ring were generally less potent than the pyrido[4,3-a]phenazines. A 4-methoxypyrido[4,3-a]phenazine (IC(50)s 2.5-26 nM) gave modest (ca. 5 day) growth delays in H69/P xenografts with oral dosing.

  13. STS-33 Discovery, OV-103, approaches concrete runway 04 at EAFB, California

    NASA Image and Video Library

    1989-11-27

    STS033-S-014 (27 Nov 1989) --- The Space Shuttle Discovery is silhouetted against late afternoon California skies as it approaches the runway for landing at Edwards Air Force Base in southern California. A five-member crew aboard was about to complete the DOD-devoted STS-33 mission. The landing occurred at 16:31:02 p.m. (PST), Nov. 27, 1989. Onboard Discovery for the mission were Astronauts Frederick D. Gregory, John E. Blaha, Kathryn C. Thornton, F. Story Musgrave and Manley L. Carter.

  14. 4-(3,4-Dihydro-β-carbolin-1-yl)pyrimidin-2-amine.

    PubMed

    Mukhtar, Mat Ropi; Zainal Abidin, Anissuhailin; Awang, Khalijah; A Hadi, A Hamid; Ng, Seik Weng

    2009-02-25

    The mol-ecule of accanthomine A, C(15)H(13)N(5), is approximately planar, with the indolyl fused-ring and the pyrimidyl ring being twisted by 31.7 (1)° The amino group of the five-membered ring is an intramolecular hydrogen-bond donor to a nitro-gen acceptor of the pyrimide ring. The amino group of the pyrimide ring is a hydrogen-bond donor to the N atoms of adjacent mol-ecules. These hydrogen-bonding inter-actions give rise to a layered network with a 4.8(2) topology.

  15. Crystal structure of methyl 3′-benzamido-4′-(4-meth­oxy­phen­yl)-1′-methyl­spiro­[indeno­[1,2-b]quinoxaline-11,2′-pyrrolidine]-3′-carboxyl­ate

    PubMed Central

    Chandralekha, Kuppan; Sureshbabu, Adukamparai Rajukrishnan; Gavaskar, Deivasigamani; Lakshmi, Srinivasakannan

    2016-01-01

    In the title compound, C35H30N4O3, the spiro C atom connects the five-membered pyrrolidine ring and the indeno­quinoxaline ring system. The pyrrolidine ring adopts a twist conformation. An intra­molecular N—H⋯N inter­action between the amino group and the pyrazine ring is observed. In the crystal, mol­ecules are linked by a pairs of C—H⋯O hydrogen bonds, forming inversion dimers. PMID:27920911

  16. Impact of metal-alkoxide functionalized linkers on H2 binding: A density functional study

    NASA Astrophysics Data System (ADS)

    Banu, Tahamida; Ghosh, Avik; Das, Abhijit K.

    2016-08-01

    The effect of metal-alkoxide functionalization of different organic linkers on the H2 binding is investigated employing DFT approach. While analyzing the H2 binding interaction of magnesium-alkoxide modified benzene, naphthalene, anthracene and pyrene linkers, we find their comparable affinity toward H2 molecules. Six-member alkoxide ring containing naphthalene and pyrene systems interact with the H2 molecules in a comparatively better way than their five-member analogues. AIM, NBO and LMO-EDA analyses have been performed to comprehend the bonding nature between Mg center and the H2 molecules. Polarization along with the charge transfer interactions play significant role in stabilizing the systems.

  17. STS-26 Mission Control Center (MCC) activity at JSC

    NASA Image and Video Library

    1988-10-02

    STS026-S-101 (2 Oct 1988) --- Flight controllers in the Johnson Space Center?s mission control center listen to a presentation by the five members of the STS 26 crew on the fourth day of Discovery?s orbital mission. Flight Directors Charles W. Shaw and James M. (Milt) Heflin (in the foreground) and other controllers view a television image of Earth on a screen in the front of the flight control room while each member relates some inner feelings while paying tribute to the Challenger crew.

  18. Theoretical study of amino derivatives and anticancer platinum drug grafted on various carbon nanostructures.

    PubMed

    Kraszewski, S; Duverger, E; Ramseyer, C; Picaud, F

    2013-11-07

    Density functional theory calculations with van der Waals approximation have been conducted to analyze the functionalization of various carbon-based nanostructures (fullerene, metallic, and semi-conducting nanotubes) with amino derivative groups. The results obtained with azomethine, show the formation of a five membered ring on fullerenes, and on nanotubes consistent with experimental observations. The attachment of an azomethine plus subsequent drug like a Pt(IV) complex does not perturb the cycloaddition process. Moreover, all theoretical results show that the length of different amino derivatives with subsequent Pt(IV) complex does not affect the complexed therapeutic agent when it is attached onto these carbon-based nanostructures.

  19. Mechanism for chelated sulfate formation from SO2 and bis (triphenylphosphine) platinum

    NASA Technical Reports Server (NTRS)

    Mehandru, S. P.; Anderson, A. B.

    1985-01-01

    Structure and energy surface calculations using the atom superposition and electron delocalization molecular orbital theory show that the first step in the reaction between SO2 and the dioxygen complex (PPh3)2PtO2 is the coordination of SO2 with one oxygen atom of the complex, followed by metal-oxygen bond breaking and reorientation, leading to a five-membered cyclic structure. This then rearranges to form the bidentate coordinated sulfate. Alternative pathways are considered and are found to be less favorable.

  20. Improved Mechanical Properties and Ozone Resistance of Radiation Cured SBR

    DTIC Science & Technology

    1991-08-01

    in an electrophilic attack, a carbonium in (I) or a complex (TT) can be 6 the first intermediate : o4-/ >0 02C C Cr) (It) This was first proposed by...the formation of five-membered cyclic intermediates (I&II) 0-0 \\ \\ \\c II and he concluded that (I) decomposes into a carbonyl and biradical: 0.0 0 0...0 [--_ - -C. O=C / \\ / This scission reaction produces a ketone as ori( ui its products. 7 Another well known mechanism is the one proposed by Criegee

  1. 3-O-Benzyl-6-O-benzoyl-1,2-O-isopropil­idene-5-C-nitro­methyl-a-d-glucofuran­ose

    PubMed Central

    Pampín, Begoña; Valencia, Laura; Estévez, Juan C.; Estévez, Ramón J.

    2009-01-01

    The title compound, C24H27NO9, is one of the epimers of the Henry reaction of 3-O-benzyl-6-O-benzoyl-2-O-isopropyl­idene-a-d-glucofuran-5-one with nitro­methane. The conformation of the five membered rings is as expected from the precursor compound and the mol­ecule is folded with a dihedral angle of 51.4 (2)° between the aromatic rings. One O—H⋯O hydrogen bond and some intra­molecular and inter­molecular C—H⋯O inter­actions are observed in the structure. PMID:21581936

  2. Catalytic Intramolecular Ketone Alkylation with Olefins by Dual Activation.

    PubMed

    Lim, Hee Nam; Dong, Guangbin

    2015-12-07

    Two complementary methods for catalytic intramolecular ketone alkylation reactions with unactivated olefins, resulting in Conia-ene-type reactions, are reported. The transformations are enabled by dual activation of both the ketone and the olefin and are atom-economical as stoichiometric oxidants or reductants are not required. Assisted by Kool's aniline catalyst, the reaction conditions can be both pH- and redox-neutral. A broad range of functional groups are thus tolerated. Whereas the rhodium catalysts are effective for the formation of five-membered rings, a ruthenium-based system that affords the six-membered ring products was also developed.

  3. An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

    PubMed Central

    2013-01-01

    Summary This review which is the second in this series summarises the most common synthetic routes as applied to the preparation of many modern pharmaceutical compounds categorised as containing a six-membered heterocyclic ring. The reported examples are based on the top retailing drug molecules combining synthetic information from both scientific journals and the wider patent literature. It is hoped that this compilation, in combination with the previously published review on five-membered rings, will form a comprehensive foundation and reference source for individuals interested in medicinal, synthetic and preparative chemistry. PMID:24204439

  4. Various views of STS-95 Senator John Glenn during training

    NASA Image and Video Library

    1998-06-18

    S98-08735 (9 April 1998) --- Five members of the STS-95 crew participate in a food tasting session at NASA's Johnson Space Center. From the left are Pedro Duque, a mission specialist representing the European Space Agency (ESA); Scott E. Parazynski, mission specialist; Steven W. Lindsey, pilot; Stephen K. Robinson, mission specialist; and payload specialist Chiaki Mukai of Japan's National Space Development Agency (NASDA). At the session but not pictured are U.S. Sen. John H. Glenn Jr., payload specialist; and Curtis L. Brown Jr., commander. The photo was taken by Joe McNally, National Geographic, for NASA.

  5. Rotational spectrum of cis-cis HOONO

    NASA Astrophysics Data System (ADS)

    Drouin, Brian J.; Fry, Juliane L.; Miller, Charles E.

    2004-03-01

    The pure rotational spectrum of cis-cis peroxynitrous acid, HOONO, has been observed. Over 220 transitions, sampling states up to J'=67 and Ka'=31, have been fitted with an rms uncertainty of 48.4 kHz. The experimentally determined rotational constants agree well with ab initio values for the cis-cis conformer, a five-membered ring formed by intramolecular hydrogen bonding. The small, positive inertial defect Δ=0.075667(60) amu Å2 and lack of any observable torsional splittings in the spectrum indicate that cis-cis HOONO exists in a well-defined planar structure at room temperature.

  6. Landing of the Shuttle Atlantis and the end of the STS 51-J mission

    NASA Image and Video Library

    1985-10-08

    S85-41803 (7 Sept 1985) --- George W.S. Abbey, bottom right, greets the five members of the STS 51-J crew as they egress the Atlantis following the successful completion of a mission in Earth orbit. Astronaut Karol J. Bobko, who led the five down the steps, shakes hands with the JSC director of flight crew operations. He is followed (bottom to top) By Astronauts Ronald J. Grabe, pilot; David C. Hilmers and Robert L. Stewart, both mission specialists; and USAF Maj. William A. Pailes, payload specialist.

  7. Biological action of inosine analogs in Leishmania and Trypanosoma spp.

    PubMed Central

    Marr, J J; Berens, R L; Cohn, N K; Nelson, D J; Klein, R S

    1984-01-01

    Previous investigations have suggested that inosine analogs would be good models for the development of chemotherapeutic agents active against pathogenic hemoflagellates. We have systematically modified the five-membered heterocyclic ring of six inosine analogs and tested them for their antiprotozoal activities and toxicity to a mammalian cell line. All six analogs were very active against the three protozoan pathogens Leishmania donovani, Trypanosoma cruzi, and Trypanosoma gambiense. Two of the six, 9-deazainosine and allopurinol ribonucleoside, had very little toxicity for mouse L cells and offer promise as potential chemotherapeutic agents. PMID:6712205

  8. Design of the strongest organic Brønsted acids in gas phase

    NASA Astrophysics Data System (ADS)

    Valadbeigi, Younes

    2017-08-01

    A new type of organic Brønsted acids is proposed exhibiting very high acidity in gas phase. The calculated gas phase enthalpies (ΔHacid) of deprotonation were 220-240 kcal/mol for the proposed acids with -CN substituents indicating that they can rival the inorganic carborane acid derivatives in gas phase. The hyperacidity of these compounds rises from the extra stability of the corresponding conjugate bases due to formation of a hydrogen bonding network and an aromatic five-membered ring.

  9. Crystal structure of the stimulatory complex of GTP cyclohydrolase I and its feedback regulatory protein GFRP.

    PubMed

    Maita, Nobuo; Okada, Kengo; Hatakeyama, Kazuyuki; Hakoshima, Toshio

    2002-02-05

    In the presence of phenylalanine, GTP cyclohydrolase I feedback regulatory protein (GFRP) forms a stimulatory 360-kDa complex with GTP cyclohydrolase I (GTPCHI), which is the rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin. The crystal structure of the stimulatory complex reveals that the GTPCHI decamer is sandwiched by two GFRP homopentamers. Each GFRP pentamer forms a symmetrical five-membered ring similar to beta-propeller. Five phenylalanine molecules are buried inside each interface between GFRP and GTPCHI, thus enhancing the binding of these proteins. The complex structure suggests that phenylalanine-induced GTPCHI x GFRP complex formation enhances GTPCHI activity by locking the enzyme in the active state.

  10. Study of ester crosslinking reactions on aluminum surfaces by infrared attenuated total reflectance spectrometry

    NASA Astrophysics Data System (ADS)

    Bhat, Sanmitra A.; Yang, Charles Q.; de Haseth, James A.

    1998-06-01

    Polycarboxylic acids are used as an alternative nonformaldehyde durable press finishing agents for cotton fabrics. Previous studies have shown that polycarboxylic acids esterify with cotton cellulose through intermediate formation of a cyclic anhydride. Cotton cellulose, due to the presence of hydroxyl groups, is a very active substrate. To understand the mechanism of ester formation, esterification reactions were studied on aluminum surfaces by infrared attenuated total reflectance (ATR) spectrometry. The infrared data showed that a five-membered cyclic anhydride is formed as an intermediate, that esterifies with the crosslinking agents. The data also demonstrated that formation of anhydride increases with temperature and also in the presence of a catalyst.

  11. Hydrogen-bonded clusters of ferrocenecarboxylic acid on Au(111).

    PubMed

    Quardokus, Rebecca C; Wasio, Natalie A; Christie, John A; Henderson, Kenneth W; Forrest, Ryan P; Lent, Craig S; Corcelli, Steven A; Kandel, S Alex

    2014-09-14

    Self-assembled monolayers of ferrocenecarboxylic acid (FcCOOH) contain two fundamental units, both stabilized by intermolecular hydrogen bonding: dimers and cyclic five-membered catemers. At surface coverages below a full monolayer, however, there is a significantly more varied structure that includes double-row clusters containing two to twelve FcCOOH molecules. Statistical analysis shows a distribution of cluster sizes that is sharply peaked compared to a binomial distribution. This rules out simple nucleation-and-growth mechanisms of cluster formation, and strongly suggests that clusters are formed in solution and collapse into rows when deposited on the Au(111) surface.

  12. Complete (1) H NMR assignment of cedranolides.

    PubMed

    Perez-Hernandez, Nury; Gordillo-Roman, Barbara; Arrieta-Baez, Daniel; Cerda-Garcia-Rojas, Carlos M; Joseph-Nathan, Pedro

    2017-03-01

    Complete and unambiguous (1) H NMR chemical shift assignment of α-cedrene (2) and cedrol (9), as well as for α-pipitzol (1), isocedrol (10), and the six related compounds 3-8 has been established by iterative full spin analysis using the PERCH NMR software (PERCH Solutions Ltd., Kuopio, Finland). The total sets of coupling constants are described and correlated with the conformational equilibria of the five-membered ring of 1-10, which were calculated using the complete basis set method. Copyright © 2015 John Wiley & Sons, Ltd.

  13. Theoretical study of amino derivatives and anticancer platinum drug grafted on various carbon nanostructures

    NASA Astrophysics Data System (ADS)

    Kraszewski, S.; Duverger, E.; Ramseyer, C.; Picaud, F.

    2013-11-01

    Density functional theory calculations with van der Waals approximation have been conducted to analyze the functionalization of various carbon-based nanostructures (fullerene, metallic, and semi-conducting nanotubes) with amino derivative groups. The results obtained with azomethine, show the formation of a five membered ring on fullerenes, and on nanotubes consistent with experimental observations. The attachment of an azomethine plus subsequent drug like a Pt(IV) complex does not perturb the cycloaddition process. Moreover, all theoretical results show that the length of different amino derivatives with subsequent Pt(IV) complex does not affect the complexed therapeutic agent when it is attached onto these carbon-based nanostructures.

  14. Coarctate cyclization reactions: a primer.

    PubMed

    Young, Brian S; Herges, Rainer; Haley, Michael M

    2012-10-04

    The cleavage of five-membered heterocycles possessing an exocyclic carbene or nitrene to form conjugated ene-ene-yne systems has been documented for over 40 years; however, the reverse reaction, using a conjugated "ene-ene-yne" precursor to form a heterocycle is a relatively new approach. Over the past decade, the Haley and Herges groups have studied computationally and experimentally the cyclization of the "hetero-ene-ene-yne" motif via an unusual class of concerted reactions known as coarctate reactions. This feature article details our synthetic and mechanistic work involving triazene-arene-alkynes and structurally-related systems to generate heterocycles using coarctate chemistry.

  15. 8-Bromo-3,4-dihydro-2H-1,3-thia­zino[2,3:2′,1′]imidazo[5′,4′-b]pyridine

    PubMed Central

    Ghacham, Hend Bel; Rodi, Youssef Kandri; Capet, Frédéric; Essassi, El Mokhtar; Ng, Seik Weng

    2010-01-01

    The imidazopyridine ring system in the title compound, C9H8BrN3S, is almost planar [r.m.s. deviation of the C and N atoms = 0.007 (1) Å]. The S and methyl­ene C atoms connected to the five-membered ring lie within this plane. The remaining two methyl­ene groups of the thia­zine ring are disordered over two sets of sites in a 0.817 (5):0.183 (5) ratio. PMID:21579133

  16. 1,3-Bis[3-(1,3-dioxoisoindolin-2-yl)prop­yl]-1H-anthra[1,2-d]imidazole-2,6,11(3H)-trione

    PubMed Central

    Afrakssou, Zahra; Rodi, Youssef Kandri; Capet, Frédéric; Essassi, El Mokhtar; Ng, Seik Weng

    2011-01-01

    The title compound, C37H26N4O7, is a 1H-anthra[2,1-d]imidazole-2,6,11(3H)-trione derivative having isoindolindionylpropyl substitutents attached to the imidazole N atoms. The anthraquinone fragment is buckled, the dihedral angle between the two benzene rings being 1.6 (1)°. The two isoindoline rings of the substituents of the imidazole ring are positioned on opposite sides of the five-membered ring; these are nearly mutually perpendicular [dihedral angle between isoindoline rings = 88.3 (1)°]. PMID:22091154

  17. LC-UV-Guided Isolation and Structure Determination of Lancolide E: A Nortriterpenoid with a Tetracyclo[5.4.0.0(2,4).0(3,7)]undecane-Bridged System from a "Talented" Schisandra Plant.

    PubMed

    Shi, Yi-Ming; Cai, Song-Liang; Li, Xiao-Nian; Liu, Miao; Shang, Shan-Zhai; Du, Xue; Xiao, Wei-Lie; Pu, Jian-Xin; Sun, Han-Dong

    2016-01-04

    Lancolide E (1) featuring a complex tetracyclo[5.4.0.0(2,4).0(3,7)]undecane-bridged system that is constructed by an eight-, a three-, and two five-membered carbon rings in a sterically congested region was obtained in trace amounts from a "talented" schinortriterpenoid producer Schisandra lancifolia. Its structure was fully characterized by combining 2D NMR spectroscopy, theoretical calculations, and X-ray diffraction analysis. The biogenetic pathway of 1 was proposed to involve a Prins cyclization.

  18. KSC-00pp1812

    NASA Image and Video Library

    2000-11-30

    KENNEDY SPACE CENTER, Fla. -- Blue mach diamonds signal the speed and force at which Space Shuttle Endeavour roars into space after a perfect launch. Liftoff occurred on time at 10:06:01 p.m. EST. The Shuttle and its five-member crew will deliver U.S. solar arrays to the International Space Station and be the first Shuttle crew to visit the Station’s first resident crew. The 11-day mission includes three spacewalks. This marks the 101st mission in Space Shuttle history and the 25th night launch. Endeavour is expected to land at KSC Dec. 11 at 6:19 p.m. EST

  19. KSC00pp1812

    NASA Image and Video Library

    2000-11-30

    KENNEDY SPACE CENTER, Fla. -- Blue mach diamonds signal the speed and force at which Space Shuttle Endeavour roars into space after a perfect launch. Liftoff occurred on time at 10:06:01 p.m. EST. The Shuttle and its five-member crew will deliver U.S. solar arrays to the International Space Station and be the first Shuttle crew to visit the Station’s first resident crew. The 11-day mission includes three spacewalks. This marks the 101st mission in Space Shuttle history and the 25th night launch. Endeavour is expected to land at KSC Dec. 11 at 6:19 p.m. EST

  20. POST-FLIGHT (CREW) - STS-8

    NASA Image and Video Library

    1983-09-05

    S83-39696 (5 Sept 1983) --- The five member astronaut crew of the Space Shuttle Challenger for STS-8 responds to a comment made by President Ronald Reagan during a post flight telephone conversation with the chief executive. The five astronauts earlier today landed the reusable spacecraft at Edwards Air Force Base in California and were flown to JSC via NASA aircraft. Richard H. Truly, center, is crew commander. Pilot for the six day flight was Daniel C. Brandenstein, second left. The mission specialist were Guion S. Bluford, left: Dr. William S. Thornton, second right, and Dale A. Gardner, right. Photo credit: NASA

  1. POST-FLIGHT (CREW) - STS-8

    NASA Image and Video Library

    1983-09-05

    S83-39693 (5 Sept 1983) --- The five member astronaut crew of the Space Shuttle Challenger for STS-8 responds to a comment made by President Ronald Reagan during a post flight telephone conversation with the chief executive. The five astronauts earlier today landed the reusable spacecraft at Edwards Air Force Base in California and were flown to JSC via NASA aircraft. Richard H. Truly, center, is crew commander. Pilot for the six day flight was Daniel C. Brandenstein, second left. The mission specialist were Guion S. Bluford, left: Dr. William S. Thornton, second right, and Dale A. Gardner, right.

  2. STS-93 Flight Day 2 Highlights and Crew Activities

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Following an eight hour sleep period, the five member flight crew, Commander Eileen Collins, Pilot Jeff Ashby, and Mission Specialists Cady Coleman, Steve Hawley and Michael Tognini awakened to begin their second day in space. The main focus of Flight Day 2 activities was to activate the secondary payloads and experiments. Among those efforts was the set-up and first observations using the Southwest Ultraviolet Imaging System (SWUIS), which operates from inside the shuttle cabin. The specific targets observed included the Earth's moon, Mercury, Venus and Jupiter. A break was taken at 4:36 a.m. CDT by Collins and Coleman to do interviews with reporters from 4 major networks.

  3. SAP family proteins.

    PubMed

    Fujita, A; Kurachi, Y

    2000-03-05

    Thus far, five members including Dlg, SAP97/hDlg, SAP90/PSD-95, SAP102, and PSD-93/chapsyn110 which belong to SAP family have been identified. Recent studies have revealed that these proteins play important roles in the localization and function of glutamate receptors and K(+) channels. Although most of them have been reported to be localized to the synapse, only one member, SAP97, is expressed also in the epithelial cells. In this review, we have summarized structural characters of SAP family proteins and discuss their functions in neurons and epithelial cells.

  4. Beyond the Divinyl Ketone: Innovations in the Generation and Nazarov Cyclization of Pentadienyl Cation Intermediates

    PubMed Central

    Spencer, William T.; Vaidya, Tulaza; Frontier, Alison J.

    2013-01-01

    The requirement for new strategies for synthesizing five-membered carbocycles has driven an expansion in the study of the Nazarov cyclization. This renewed interest in the reaction has led to the discovery of several interesting new methods for generating the pentadienyl cation intermediate central to the cyclization. Methods reviewed include carbon-heteroatom ionization, functionalization of a double bond, nucleophilic addition, or electrocyclic ring opening. Additional variations employ unconventional substrates to produce novel pentacycles, such as the iso- and imino-Nazarov. Herein, we provide an overview of these unconventional, yet highly useful versions of the Nazarov cyclization. PMID:24348092

  5. Crystal structure of 2-ethyl-4-methyl-1-(2-oxido-3,4-dioxo­cyclo­but-1-en-1-yl)-1H-imidazol-3-ium

    PubMed Central

    Korkmaz, Ufuk; Bulut, Iclal; Bulut, Ahmet

    2016-01-01

    In the title inner salt molecule, C10H10N2O3, the four-membered cyclobutene ring is twisted by 7.1 (2)° with respect to the five-membered imidazole ring. The crystal packing exhibits an R 2 2(9) hydrogen-bonding ring motif through N—H⋯O and C—H⋯O inter­actions. The potential non-linear optical properties were studied by a computational ab initio calculations performed at the DFT/B3LYP/6–31++G(d,p) level of theory. PMID:27555949

  6. Theoretical study on the catalytic reactivity of N-hydroxyphthalimide tuned by different heterocyclic substitutions on its phenyl ring for aerobic oxidation

    NASA Astrophysics Data System (ADS)

    Chen, Kexian; Xie, Haiying; Jiang, Kezhi; Mao, Jianyong

    2016-07-01

    The structure-reactivity relationship of new hydroxyimide organocatalysts based on the heterocyclic replacements of the phenyl ring of N-hydroxyphthalimide (NHPI) has been theoretically investigated to gain a mature understanding of this particular catalysis for aerobic oxidation. We find that the reactivity of catalysts with the common five-member aromatic rings is lower than that of NHPI. The catalyst with the recyclable structure of imidazolium ionic liquid may serve as a novel model catalyst for further improvements due to its reactivity comparable to that of NHPI. The catalytic reactivity of multi-nitroxyl catalysts is theoretically more fascinating than that of the highly efficient N,N-dihydroxypyromellitimide.

  7. Cathepsin proteases in Toxoplasma gondii

    PubMed Central

    Dou, Zhicheng; Carruthers, Vern B.

    2014-01-01

    Cysteine proteases are important for the growth and survival of apicomplexan parasites that infect humans. The apicomplexan Toxoplasma gondii expresses five members of the C1 family of cysteine proteases, including one cathepsin L-like (TgCPL), one cathepsin B-like (TgCPB), and three cathepsin C-like (TgCPC1, 2 and 3) proteases. Recent genetic, biochemical and structural studies reveal that cathepsins function in microneme and rhoptry protein maturation, host cell invasion, replication, and nutrient acquisition.. Here, we review the key features and roles of T. gondii cathepsins and discuss the therapeutic potential for specific inhibitor development. PMID:21660658

  8. The marriage of metallacycle transfer chemistry with Suzuki-Miyaura cross-coupling to give main group element-containing conjugated polymers.

    PubMed

    He, Gang; Kang, Le; Torres Delgado, William; Shynkaruk, Olena; Ferguson, Michael J; McDonald, Robert; Rivard, Eric

    2013-04-10

    A versatile and general synthetic route for the synthesis of conjugated main group element-based polymers, previously inaccessible by conventional means, is reported. These polymers contain five-membered chalcogenophene rings based on S, Se, and Te, and we demonstrate that optoelectronic properties can be readily tuned via controlled atom substitution chemistry. In addition, regioregular hybrid thiophene-selenophene-tellurophene and selenophene-fluorene copolymers were synthesized to provide a further illustration of the scope of the presented metallacycle transfer/cross-coupling polymerization method.

  9. For Debate: Impotence in Farm Workers using Toxic Chemicals

    PubMed Central

    Espir, Michael L. E.; Hall, J. W.; Shirreffs, J. G.; Stevens, David L.

    1970-01-01

    Four out of five members of a team of farmworkers who had been using various herbicides and pesticides in intensive agriculture became impotent. Sexual function recovered after further contact with the chemicals was stopped and hormone therapy had been given, though in one case this took about a year. We have not been able to incriminate one particular substance, but with the circumstantial evidence and the lack of any other obvious cause it seems likely that the impotence was due to the toxic effects of one or more of the chemicals being used. PMID:5434665

  10. The anisotropic effect of functional groups in 1H NMR spectra is the molecular response property of spatial nucleus independent chemical shifts (NICS)--conformational equilibria of exo/endo tetrahydrodicyclopentadiene derivatives.

    PubMed

    Kleinpeter, Erich; Lämmermann, Anica; Kühn, Heiner

    2011-02-21

    The inversion of the flexible five-membered ring in tetrahydrodicyclopentadiene (TH-DCPD) derivatives remains fast on the NMR timescale even at 103 K. Since the intramolecular exchange process could not be sufficiently slowed for spectroscopic evaluation, the conformational equilibrium is thus inaccessible by dynamic NMR. Fortunately, the spatial magnetic properties of the aryl and carbonyl groups attached to the DCPD skeleton can be employed in order to evaluate the conformational state of the system. In this context, the anisotropic effects of the functional groups in the (1)H NMR spectra prove to be the molecular response property of spatial nucleus independent chemical shifts (NICS).

  11. Light-induced ruthenium-catalyzed nitrene transfer reactions: a photochemical approach towards N-acyl sulfimides and sulfoximines.

    PubMed

    Bizet, Vincent; Buglioni, Laura; Bolm, Carsten

    2014-05-26

    1,4,2-Dioxazol-5-ones are five-membered heterocycles known to decarboxylate under thermal or photochemical conditions, thus yielding N-acyl nitrenes. Described herein is a light-induced ruthenium-catalyzed N-acyl nitrene transfer to sulfides and sulfoxides by decarboxylation of 1,4,2-dioxazol-5-ones at room temperature, thus providing direct access to N-acyl sulfimides and sulfoximines under mild reaction conditions. In addition, a one-pot sulfur imidation/oxidation sequence catalyzed by a single ruthenium complex is reported. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. 1,3-Dipolar cycloaddition of a cyclic nitrone derived from 2-deoxy-D-ribose to α,β-unsaturated lactones: An entry to carbapenem antibiotics.

    PubMed

    Pieczykolan, Michał; Staszewska-Krajewska, Olga; Furman, Bartłomiej; Chmielewski, Marek

    2016-10-04

    1,3-Dipolar cycloadditions of 2-deoxy-D-ribose-derived L-threo five-membered cyclic nitrone to α,β-unsaturated γ- and δ-lactones were investigated. Cycloadducts obtained from δ-lactones, after NO bond cleavage, opening of the lactone ring, and protection of hydroxyl groups were subjected to β-lactam ring formation by using Mukaiyama's salt. Cycloadducts from γ-lactones subjected to the same reaction sequence undergo β-elimination of a water molecule to provide pyrrolidine-substituted unsaturated γ-lactones. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. N-(4-Bromo-phen-yl)-2-[(1-cyclo-hexyl-meth-yl-1H-1,2,4-triazol-3-yl)sulfanyl]-acetamide.

    PubMed

    Wang, Yue-Ping; Yan, Wan-Lu; Guo, Qiong; He, Yan-Ping

    2012-05-01

    The title compound, C(17)H(21)BrN(4)OS, was synthesized as a potential reverse transcriptase (RT) inhibitor of the human immunodeficiency virus type 1 (HIV-1). In the molecule, there is an N-H⋯S hydrogen bond making a five-membered ring. In the crystal, mol-ecules are connected into centrosymmetric dimers via pairs of N-H⋯N and weak C-H⋯N hydrogen bonds. The crystal structure also features C-H⋯O inter-actions.

  14. Hybrid [5]Radialenes with Bispyrroloheteroles: New Electron-Donating Units.

    PubMed

    Higashino, Tomohiro; Imahori, Hiroshi

    2015-09-14

    Bispyrroloheteroles have been synthesized to address their intrinsic structural, optical, and electrochemical properties. The X-ray crystal structures and calculated natural bond orbital (NBO) bond orders unambiguously demonstrated the existence of a two pyrrole-fused five-membered ring with short exocyclic C-C double bonds and long endocyclic C-C single bonds, supporting that the bispyrroloheteroles are rare examples of structurally characterized hybrid [5]radialenes. The bispyrroloheteroles were found to act as an electron-donating unit, which would be fascinating for the rational design of new charge-transporting and donor-acceptor photovoltaic materials as well as versatile charge-transfer complexes.

  15. Method for controlling clathrate hydrates in fluid systems

    DOEpatents

    Sloan, Jr., Earle D.

    1995-01-01

    Discussed is a process for preventing clathrate hydrate masses from impeding the flow of fluid in a fluid system. An additive is contacted with clathrate hydrate masses in the system to prevent those clathrate hydrate masses from impeding fluid flow. The process is particularly useful in the natural gas and petroleum production, transportation and processing industry where gas hydrate formation can cause serious problems. Additives preferably contain one or more five member and/or six member cyclic chemical groupings. Additives include poly(N-vinyl-2-pyrrolidone) and hydroxyethylcellulose, either in combination or alone.

  16. First Insertions of Carbene Ligands into Ge-N and Si-N Bonds.

    PubMed

    Álvarez-Rodríguez, Lucía; Cabeza, Javier A; García-Álvarez, Pablo; Gómez-Gallego, Mar; Merinero, Alba D; Sierra, Miguel A

    2017-03-28

    The insertion of carbene ligands into Ge-N (three examples) and Si-N (one example) bonds has been achieved for the first time by treating Fischer carbene complexes (M=W, Cr) with bulky amidinatotetrylenes (E=Ge, Si). These reactions, which start with a nucleophilic attack of the amidinatotetrylene heavier group 14 atom to the carbene C atom, proceed through a stereoselective insertion of the carbene fragment into an E-N bond of the amidinatotetrylene ENCN four-membered ring, leading to [M(CO)5 L] derivatives in which L belongs to a novel family of tetrylene ligands comprising an ECNCN five-membered ring.

  17. Post-transcriptional regulation of ethylene perception and signaling in Arabidopsis

    SciTech Connect

    Schaller, George Eric

    2014-03-19

    The simple gas ethylene functions as an endogenous regulator of plant growth and development, and modulates such energy relevant processes as photosynthesis and biomass accumulation. Ethylene is perceived in the plant Arabidopsis by a five-member family of receptors related to bacterial histidine kinases. Our data support a general model in which the receptors exist as parts of larger protein complexes. Our goals have been to (1) characterize physical interactions among members of the signaling complex; (2) the role of histidine-kinase transphosphorylation in signaling by the complex; and (3) the role of a novel family of proteins that regulate signal output by the receptors.

  18. Ab Initio Direct Trajectory Simulation on Hydrogen Atom Transfer in 7-Azaindole in the Electronic Excited State with Assist of Water Molecules

    DTIC Science & Technology

    2006-07-14

    dynamical process of proton transfer in 7AI-(H2O)n systems, i.e., a hydrogen atom transfer from a five-membered ring to a six-membered ring in 7AI assisted...were carried out for 7AI-(H2O)2 in the ground state by the RHF method with Tatewaki’s valence-double-zeta plus polarization (DZP) basis sets, and two...transfer process . The results will be published in near future. 2. Vibrational analysis of 7AI-H2O complex: anharmonicities using quartic force field

  19. Crystal structure of 4-{[(cyano­imino)(methyl­sulfanyl)meth­yl]amino}-1,5-dimethyl-2-phenyl-2,3-di­hydro-1H-pyrazol-3-one

    PubMed Central

    Elgemeie, Galal H.; Abouzeid, Mamdouh; Jones, Peter G.

    2015-01-01

    In the title compound, C14H15N5OS, the tautomer present in the solid state is that in which the immediately exocyclic N atom bears the H atom. The central five-membered ring is almost planar (r.m.s. deviation = 0.025 Å), but both its N atoms are significantly pyramidalized. A classical hydrogen bond from the N—H group to the cyanide N atom forms inversion-symmetric dimers, which are further linked by C—H⋯O inter­actions. PMID:25705464

  20. Synthesis of new pyrazolyl-1,3-diazabicyclo[3.1.0]hexe-3-ene derivatives

    NASA Astrophysics Data System (ADS)

    Kiyani, Hamzeh; Albooyeh, Fereshteh; Fallahnezhad, Saied

    2015-07-01

    A series of new of photochromic 1,3-diazabicyclo[3.1.0]hex-3-ene derivatives based on the skeleton of five-membered pyrazole moiety have been synthesized and characterized by spectral techniques, as well as their photochromic properties were examined under UV light irradiation in various solutions. All these newly synthesized compounds showed good photochromic properties in the both solution and solid states. The UV-Visible spectral analysis of the corresponding pyrazolyl bicyclic aziridines established structure-photochromic behavior relationships.