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Kinds of Table Terms modified by Table Selected AbstractsETHICS OF ALCOHOL POLICY IN BRAZIL: WHY IT IS POSSIBLE TO BE INDEPENDENT WHEN WE SIT AT THE SAME TABLE WITH THE ALCOHOL INDUSTRYADDICTION, Issue 5 2008ARTHUR GUERRA DE ANDRADE No abstract is available for this article. [source] A MODEL LIFE TABLE FOR BOTTLENOSE DOLPHINS (TURSIOPS TRUNCATUS) FROM THE INDIAN RIVER LAGOON SYSTEM, FLORIDA, U.S.A.MARINE MAMMAL SCIENCE, Issue 4 2003Megan K. Stolen Abstract Data gathered from 220 stranded bottlenose dolphins (Tursiops truncatus) in the Indian River Lagoon system, Florida, were used to derive a life table. Survivorship curves were fit to the data using Siler's competing-risk model and a maximum likelihood approach. Population growth was estimated to be between r= 0.0 and 0.046 based on the observed numbers of stranded dolphins. Variance in survival rates was estimated using an individual-based, age-structured population projection model. We estimate that the overall annual mortality rate for this population was 9.8% per year. Sex-specific differences in survivorship were apparent with females outliving males. The overall mortality curve resembles that of other large mammals, with high calf mortality and an exponentially increasing risk of senescent mortality. The inclusion of live-capture removals of individuals from this population did not significantly affect the estimation of survival parameters for most age classes. [source] Direct from Farm to Table: Community Supported Agriculture in Western IllinoisCULTURE, AGRICULTURE, FOOD & ENVIRONMENT, Issue 1-2 2004Associate Professor Heather Mcllvaine-Newsad First page of article [source] Nonepileptic Disorders Imitating Generalized Idiopathic EpilepsiesEPILEPSIA, Issue 2005Natalio Fejerman Summary:, Differential diagnosis between epileptic and nonepileptic paroxysmal disorders is fundamental not only to allow correct management of patients but also to avoid the burden of unnecessary antiepileptic medication. The focus of this chapter is limited to imitators of idiopathic generalized epilepsies (IGE) which are expressed through myoclonic, tonic,clonic, tonic, atonic, and absence seizures. Apparent losses of consciousness and drop attacks also have to be considered. Benign myoclonus of early infancy is the main nonepileptic disorder in the differential diagnosis of infantile spasms, but is not dealt with here because West syndrome is not an IGE. Hyperekplexia, metabolic disorders, hypnagogic myoclonus, and disturbed responsiveness caused by the use of drugs are listed in Table 1. Other conditions that may imitate more focal epileptic seizures are omitted. Benign neonatal sleep myoclonus, apnea and apparent life-threatening events in infants, cyanotic and pallid breath-holding spells, syncope, staring spells, psychogenic seizures, hyperventilation syndrome, and narcolepsy have been selected based on frequency or difficulties in differential diagnosis with the intention to cover the most conspicuous imitators of IGE in different ages. Table 1. Nonepileptic disorders imitating idiopathic generalized epilepsies [source] Reactivity Pattern in the Room-Temperature Activation of NH3 by the Main-Group Atomic Ions Ga+, Ge+, As+ and Se+EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 10 2010Gregory K. Koyanagi Abstract The activation of ammonia by the main-group cations Ga+, Ge+, As+ and Se+ has been explored both experimentally and theoretically. ICP/SIFT tandem mass spectrometer measurements of room-temperature kinetics have revealed a substantial variation in rates and product distributions across the Periodic Table of Elements. The main features of the observed primary chemistry include H-atom elimination, ammonia addition and a cation-assisted proton transfer to yield NH4+ that is second order in ammonia. These observations are shown to be completely consistent with computed potential energy surfaces for the reactions of each of the four atomic cations. Dehydrogenation by the elimination of molecular hydrogen, not observed experimentally, is shown by the calculations to be inhibited by the presence of a kinetic barrier. [source] Reliability modelling of uninterruptible power supply systems using fault tree analysis methodEUROPEAN TRANSACTIONS ON ELECTRICAL POWER, Issue 6 2009Mohd Khairil Rahmat Abstract The aim of this paper is to investigate the reliability parameters estimation method for the uninterruptible power supply (UPS) systems using the Fault Tree Analysis (FTA) technique. FTA is a top,down approach to identify all potential causes leading to system failure. The computation of the system's failure probability is the main goal of this analysis, as this value can be used to calculate other important system reliability parameters such as failure rates, mean time between failures and reliability. In this paper, the FTA method was applied to five different UPS topologies and the results obtained were compared and discussed in detail. By comparing the critical fault path of the system, it was found that the inverter failures contributed most significantly to the system failure. It was also found that the probability of failure of a UPS system can be reduced by the inclusion of bypass supply, given that the failure rate of the events that causing the failure of the bypass supply should be lower compared to the ones for the main utility supply. Finally, to validate the results obtained from this method, comparisons were made to the results from other methods such as the Reliability Block Diagram, Boolean Truth Table, Probability Tree, Monte-Carlo Simulation and Field Data reliability estimation methods. Copyright © 2008 John Wiley & Sons, Ltd. [source] Reconstruction of the Water Table from Self-Potential Data: A Bayesian ApproachGROUND WATER, Issue 2 2009A. Jardani Ground water flow associated with pumping and injection tests generates self-potential signals that can be measured at the ground surface and used to estimate the pattern of ground water flow at depth. We propose an inversion of the self-potential signals that accounts for the heterogeneous nature of the aquifer and a relationship between the electrical resistivity and the streaming current coupling coefficient. We recast the inversion of the self-potential data into a Bayesian framework. Synthetic tests are performed showing the advantage in using self-potential signals in addition to in situ measurements of the potentiometric levels to reconstruct the shape of the water table. This methodology is applied to a new data set from a series of coordinated hydraulic tomography, self-potential, and electrical resistivity tomography experiments performed at the Boise Hydrogeophysical Research Site, Idaho. In particular, we examine one of the dipole hydraulic tests and its reciprocal to show the sensitivity of the self-potential signals to variations of the potentiometric levels under steady-state conditions. However, because of the high pumping rate, the response was also influenced by the Reynolds number, especially near the pumping well for a given test. Ground water flow in the inertial laminar flow regime is responsible for nonlinearity that is not yet accounted for in self-potential tomography. Numerical modeling addresses the sensitivity of the self-potential response to this problem. [source] Stereochemical Models for Discussing Additions to ,,, -Unsaturated Aldehydes Organocatalyzed by Diarylprolinol or Imidazolidinone Derivatives , Is There an ,(E)/(Z)-Dilemma'?HELVETICA CHIMICA ACTA, Issue 4 2010Dieter Seebach Abstract The structures of iminium salts formed from diarylprolinol or imidazolidinone derivatives and ,,, -unsaturated aldehydes have been studied by X-ray powder diffraction (Fig.,1), single-crystal X-ray analyses (Table,1), NMR spectroscopy (Tables,2 and 3, Figs.,2,7), and DFT calculations (Helv. Chim. Acta2009, 92, 1, 1225, 2010, 93, 1; Angew. Chem., Int. Ed.2009, 48, 3065). Almost all iminium salts of this type exist in solution as diastereoisomeric mixtures with (E)- and (Z)-configured +NC bond geometries. In this study, (E)/(Z) ratios ranging from 88,:,12 up to 98,:,2 (Tables,2 and 3) and (E)/(Z) interconversions (Figs.,2,7) were observed. Furthermore, the relative rates, at which the (E)- and (Z)-isomers are formed from ammonium salts and ,,, -unsaturated aldehydes, were found to differ from the (E)/(Z) equilibrium ratio in at least two cases (Figs.,4 and 5,,a, and Fig.,6,,a); more (Z)-isomer is formed kinetically than corresponding to its equilibrium fraction. Given that the enantiomeric product ratios observed in reactions mediated by organocatalysts of this type are often ,99,:,1, the (E)-iminium-ion intermediates are proposed to react with nucleophiles faster than the (Z)-isomers (Scheme,5 and Fig.,8). Possible reasons for the higher reactivity of (E)-iminium ions (Figs.,8 and 9) and for the kinetic preference of (Z)-iminium-ion formation are discussed (Scheme,4). The results of related density functional theory (DFT) calculations are also reported (Figs.,10,13 and Table,4). [source] Four New Triterpenes from Anchusa azurea var. azureaHELVETICA CHIMICA ACTA, Issue 3 2010e Kuruüzüm-Uz Abstract Four new triterpene glycosides, named oleanazuroside 1 (1), oleanazuroside 2 (2), ursolazuroside 1 (3), and ursolazuroside 2 (4), together with the seven known compounds 5,11, were isolated from the MeOH extract of the aerial parts of Anchusa azureaMiller var. azurea. Their structures were elucidated by means of spectroscopic evidence (UV, IR, MALDI-MS, and 1D- and 2D-NMR). The radical-scavenging activities against 2,2-diphenyl-1-picrylhydrazyl (DPPH) of the BuOH extract and of 8 and 10 were very strong (Table,5). [source] Peroxide/Potassium Iodide Redox Systems for in situ Oxyiodination of Organic Compounds under Liquid-Phase and Solvent-Free ConditionsHELVETICA CHIMICA ACTA, Issue 2 2010Gattu Venkateshwarlu Abstract Iodination of certain aromatic amines and phenols are triggered by the oxidation of KI by peroxy compounds such as tert -butyl hydroperoxide (tBuOOH) under liquid-phase and solvent-free conditions by grinding the reactants in a mortar with a pestle. The reactions afforded corresponding iodo derivatives in good yield with high regioselectivity (Table,1). [source] NMR-Solution Structures and Affinities for the Human Somatostatin G-Protein-Coupled Receptors hsst1,5 of CF3 Derivatives of Sandostatin® (Octreotide)HELVETICA CHIMICA ACTA, Issue 12 2009Dieter Seebach Abstract The previously reported (Helv. Chim. Acta2008, 91, 2035) derivatives of octreotide (1) with a (CF3)-Trp substitution, i.e., 3, and with open-chain structures, i.e., 2, 4, and 5, have been tested for their affinities to hsst1,5 receptors and subjected to a detailed NMR analysis. Their affinities vary from 15,nM to 5,,M, as compared to 0.6,nM to 0.8,,M for octreotide itself (Table,1). This decreased bioactivity may have had to be expected for the open-chain compounds 4 and 5; possible reasons for this decrease in the case of CF3 derivative of octreotide, 3, are discussed. NMR Analysis (Tables,2 and 3) provides evidence for increased dynamics of all new derivatives 2,5. The dynamics of the octreotide molecule 1 was analyzed by (natural-abundance) longitudinal 13C-T1 -relaxation time measurements (Table,4), from which the conclusion is drawn that the backbone of the macrocycle is rather rigid on the time scale of this method. [source] Structures of the Reactive Intermediates in Organocatalysis with Diarylprolinol EthersHELVETICA CHIMICA ACTA, Issue 7 2009Abstract Structures of the reactive intermediates (enamines and iminium ions) of organocatalysis with diarylprolinol derivatives have been determined. To this end, diarylprolinol methyl and silyl ethers, 1, and aldehydes, PhCH2CHO, tBuCH2CHO, PhCH=CHCHO, are condensed to the corresponding enamines, A and 3 (Scheme,2), and cinnamoylidene iminium salts, B and 4 (Scheme,3). These are isolated and fully characterized by melting/decomposition points, [,]D, elemental analysis, IR and NMR spectroscopy, and high-resolution mass spectrometry (HR-MS). Salts with BF4, PF6, SbF6, and the weakly coordinating Al[OC(CF3)3]4 anion were prepared. X-Ray crystal structures of an enamine and of six iminium salts have been obtained and are described herein (Figs.,2 and 4,8, and Tables,2 and 7) and in a previous preliminary communication (Helv. Chim. Acta2008, 91, 1999). According to the NMR spectra (in CDCl3, (D6)DMSO, (D6)acetone, or CD3OD; Table,1), the major isomers 4 of the iminium salts have (E)-configuration of the exocyclic NC(1,) bond, but there are up to 11% of the (Z)-isomer present in these solutions (Fig.,1). In all crystal structures, the iminium ions have (E)-configuration, and the conformation around the exocyclic N-CC-O bond is synclinal-exo (cf.C and L), with one of the phenyl groups over the pyrrolidine ring, and the RO group over the , -system. One of the meta -substituents (Me in 4b, CF3 in 4c and 4e) on a 3,5-disubstituted phenyl group is also located in the space above the , -system. DFT Calculations at various levels of theory (Tables,3,6) confirm that the experimentally determined structures (cf. Fig.,10) are by far (up to 8.3,kcal/mol) the most stable ones. Implications of the results with respect to the mechanism of organocatalysis by diarylprolinol derivatives are discussed. [source] An Efficient Synthesis of Novel Hexahydropyrido[2,3- d]pyrimidine Derivatives from (Arylmethylidene)pyruvic Acids (=(3E)-4-Aryl-2-oxobut-3-enoic Acids) in Aqueous MediaHELVETICA CHIMICA ACTA, Issue 5 2009Saeed Balalaie Abstract A series of new hexahydropyrido[2,3- d]pyrimidine derivatives 3 were synthesized by the cyclocondensation reaction of (arylmethylidene)pyruvic acids (=(3E)-4-aryl-2-oxobut-3-enoic acids) 1 and 6-aminouracils (=6-aminopyrimidine-2,4(1H,3H)-diones) 2 in H2O under reflux conditions (Scheme,1, Table). This novel protocol has the advantages of facility, of easy workup, of high yields, and of an environmentally benign procedure. The structures of compounds 3a,3f were corroborated spectroscopically (IR, 1H- and 13C-NMR, and EI-MS). A plausible mechanism for the reaction is proposed (Scheme,2). [source] 5-Benzyl-3-methylimidazolidin-4-one-Derived Reactive Intermediates of Organocatalysis , A Comforting Resemblance of X-Ray, NMR, and DFT Solid-Phase, Liquid-Phase, and Gas-Phase StructuresHELVETICA CHIMICA ACTA, Issue 1 2009Abstract The X-ray crystal structures of three (E)-1-cinnamoylidene iminium PF6 salts of 5-benzyl-3-methylimidazolidin-4-ones (2,2-dimethyl-, cis -2-(tert -butyl)-, and cis -2-styryl-substituted; 2,4, resp.) are reported (Figs.,3,5). In the 2,2-dimethyl and in the cis -2-styryl derivative, 2 and 4, respectively, a CH bond of the cis -substituent in 2-position points to the center of the benzene ring of the benzyl group above the five-membered ring (Fig.,6,,a and b). NMR Measurements (Fig.,8) provide evidence that the same structure is present in solution, and that a fourth derivative of this type, 5 (Scheme), has (Z)- instead of (E)-configuration around the CN bond. In the cis -2-(tert -butyl) derivative 3, the benzyl group is located over the iminium , -system (Figs.,4 and 6,,c). Overlays with DFT-calculated crotonylidene analogs, A and B, show that the theoretical and experimental structures are almost superimposable (Fig.,9 and Table). The structures are discussed in view of their role as reactive intermediates in organocatalysis and in view of the help synthetic organic chemists may experience from theory. [source] Isolation and X-Ray Structures of Reactive Intermediates of Organocatalysis with Diphenylprolinol Ethers and with ImidazolidinonesHELVETICA CHIMICA ACTA, Issue 11 20085-Repulsion, A Survey, Comparison with Computed Structures, the Geminal-Diaryl Effect at Work, with 1-Acyl-imidazolidinones: The Abstract Reaction of 2-phenylacetaldehyde with the Me3Si ether of diphenyl-prolinol, with removal of H2O, gives a crystalline enamine (1). The HBF4 salts of the MePh2Si ether of diphenyl-prolinol and of 2-(tert -butyl)-3-methyl- and 5-benzyl-2,2,3-trimethyl-1,3-imidazolidin-4-one react with cinnamaldehyde to give crystalline iminium salts 2, 3, and 4. Single crystals of the enamine and of two iminium salts, 2 and 3, were subjected to X-ray structure analysis (Figs.,1, 2, and 6), and a 2D-NMR spectrum of the third iminium salt was recorded (Fig.,7). The crystal and NMR structures confirm the commonly accepted, general structures of the two types of reactive intermediates in organocatalysis with the five-membered heterocycles, i.e., D, E (Scheme,2). Fine details of the crystal structures are discussed in view of the observed stereoselectivities of the corresponding reactions with electrophiles and nucleophiles. The structures 1 and 2 are compared with those of other diphenyl-prolinol derivatives (from the Cambridge File CSD; Table,1) and discussed in connection with other reagents and ligands, containing geminal diaryl groups and being used in enantioselective synthesis (Fig.,4). The iminium ions 3 and 4 are compared with N -acylated imidazolidinones F and G (Figs.,9, 12, and 13, and Table,3), and common structural aspects such as minimalization of 1,5-repulsion (the ,A1,3 -effect'), are discussed. The crystal structures of the simple diphenyl-prolinol,HBF4 salt (Fig.,3) and of Boc- and benzoyl-(tert -butyl)methyl-imidazolidinone (Boc-BMI and Bz-BMI, resp.; Figs.,10 and 11) are also reported. Finally, the crystal structures are compared with previously published theoretical structures, which were obtained from high-level-of-theory DFT calculations (Figs.,5 and 8, and Table,2). Delicate details including pyramidalization of trigonal N-atoms, distortions around iminium CN bonds, shielding of diastereotopic faces, and the , -interaction between a benzene ring and a Me group match so well with, and were actually predicting the experimental results that the question may seem appropriate, whether one will soon start considering to carry out such calculations before going to the laboratory for experimental optimizations. [source] Oligonucleotides Containing 7-Deaza-2,-deoxyinosine as Universal Nucleoside: Synthesis of 7-Halogenated and 7-Alkynylated Derivatives, Ambiguous Base Pairing, and Dye Functionalization by the Alkyne,Azide ,Click' ReactionHELVETICA CHIMICA ACTA, Issue 7 2008Frank Seela Abstract Oligonucleotides containing 7-deaza-2,-deoxyinosine derivatives bearing 7-halogen substituents or 7-alkynyl groups were prepared. For this, the phosphoramidites 2b,2g containing 7-substituted 7-deaza-2,-deoxyinosine analogues 1b,1g were synthesized (Scheme,2). Hybridization experiments with modified oligonucleotides demonstrate that all 2,-deoxyinosine derivatives show ambiguous base pairing, as 2,-deoxyinosine does. The duplex stability decreases in the order Cd>Ad>Td>Gd when 2b,2g pair with these canonical nucleosides (Table,6). The self-complementary duplexes 5,-d(F7c7I-C)6, d(Br7c7I-C)6, and d(I7c7I-C)6 are more stable than the parent duplex d(c7I-C)6 (Table,7). An oligonucleotide containing the octa-1,7-diyn-1-yl derivative 1g, i.e., 27, was functionalized with the nonfluorescent 3-azido-7-hydroxycoumarin (28) by the Huisgen,Sharpless,Meldal cycloaddition ,click' reaction to afford the highly fluorescent oligonucleotide conjugate 29 (Scheme,3). Consequently, oligonucleotides incorporating the derivative 1g bearing a terminal CC bond show a number of favorable properties: i) it is possible to activate them by labeling with reporter molecules employing the ,click' chemistry. ii) Space demanding residues introduced in the 7-position of the 7-deazapurine base does not interfere with duplex structure and stability (Table,8). iii) The ambiguous pairing character of the nucleobase makes them universal probes for numerous applications in oligonucleotide chemistry, molecular biology, and nanobiotechnology. [source] A Joint Theoretical and Experimental Insight into the Electronic Structure of Chromophores Derived from 6H,12H -5,11-Methanodibenzo[b,f][1,5]diazocineHELVETICA CHIMICA ACTA, Issue 11 2007Vincent Lemaur Abstract We report on the synthesis and electronic spectra of the chiral, donor-acceptor (push-pull) chromophores (±)- 4 and (±)- 5 with a 6H,12H -5,11-methanodibenzo[b,f][1,5]diazocine scaffold (Scheme,1 and Fig.,2). The electronic structures of these compounds were investigated at a quantum-chemical level (Figs.,2 and 3). The chemical reactivity of 6H,12H -5,11-methanodibenzo[b,f][1,5]diazocine ((±)- 11) towards aromatic electrophilic substitution (Scheme,2 and Table) provided additional information about its electronic structure and confirmed nonnegligible delocalization of the lone pair of the bridge-head N-atoms in this heterocyclic system. [source] Direct Amination of meso -Tetraarylporphyrin Derivatives , Easy Route to A3B-, A2BC-, and A2B2 -Type Porphyrins Bearing Two Nitrogen-Containing Substituents at the meso -Positioned Phenyl GroupsHELVETICA CHIMICA ACTA, Issue 10 2007Stanis, aw Ostrowski Abstract meso -Tetraarylporphyrinato complexes 1a,g (ZnII, CuII, and NiII) bearing one or two nitro-substituted aryl moieties react with 1,1,1-trimethylhydrazinium iodide in the presence of tBuOK in THF at 0,5° or in the presence of KOH in DMSO at 60,70° according to a nucleophilic substitution of an H-atom, thus affording porphyrins 2a,g and 3f,g with amino-functionalized meso -positioned aryl substituents in yields up to 73% (Scheme,1 and Table). The products obtained are attractive intermediates for further derivatization of porphyrins and may be of potential use as sensitizers in photodynamic cancer therapy. [source] Structure,Activity Relationship in the Domain of Odorants Having Marine NotesHELVETICA CHIMICA ACTA, Issue 7 2007Jean-Marc Gaudin Abstract We synthesized or re-synthesized a large series of 2H -1,5-benzodioxepin-3(4H)-ones 9 (Scheme,1), 4,5-dihydro-1-benzoxepin-3(2H)-ones 10 (Schemes 3 and 4) and 5,6,8,9-tetrahydro-7H -benzocyclohepten-7-ones 11 (Schemes 5 and 6), since the lead compound for the olfactory note of perfumes based on marine accords is a well-known benzodioxepinone named Calone 1951® (9b). We meticulously described the odor profile of each synthesized compound and discussed relevant structure,odor relationships (Tables,1,3). In particular, we revealed a correlation between the conformation of the seven-membered ring and the activities of these compounds (Table,4 and Fig.,3). We also clarified the effect of the position and the size of the alkyl substituent at the aromatic ring. [source] Structure-Based Design and Synthesis of the First Weak Non-Phosphate Inhibitors for IspF, an Enzyme in the Non-Mevalonate Pathway of Isoprenoid BiosynthesisHELVETICA CHIMICA ACTA, Issue 6 2007Corinne Baumgartner Abstract In this paper, we describe the structure-based design, synthesis, and biological evaluation of cytosine derivatives and analogues that inhibit IspF, an enzyme in the non-mevalonate pathway of isoprenoid biosynthesis. This pathway is responsible for the biosynthesis of the C5 precursors to isoprenoids, isopentenyl diphosphate (IPP, 1) and dimethylallyl diphosphate (DMAPP, 2; Scheme,1). The non-mevalonate pathway is the sole source for 1 and 2 in the protozoan Plasmodium parasites. Since mammals exclusively utilize the alternative mevalonate pathway, the enzymes of the non-mevalonate pathway have been identified as attractive new drug targets in the fight against malaria. Based on computer modeling (cf. Figs.,2 and 3), new cytosine derivatives and analogues (Fig.,1) were selected as potential drug-like inhibitors of IspF protein, and synthesized (Schemes,2,5). Determination of the enzyme activity by 13C-NMR spectroscopy in the presence of the new ligands showed inhibitory activities for some of the prepared cytosine and pyridine-2,5-diamine derivatives in the upper micromolar range (IC50 values; Table). The data suggest that it is possible to inhibit IspF protein without binding to the polar diphosphate binding site and the side chain of Asp56,, which interacts with the ribose moiety of the substrate and substrate analogues. Furthermore, a new spacious sub-pocket was discovered which accommodates aromatic spacers between cytosine derivatives or analogues (binding to ,Pocket III') and rings that occupy the flexible hydrophobic region of ,Pocket II'. The proposed binding mode remains to be further validated by X-ray crystallography. [source] Are Oxazolidinones Really Unproductive, Parasitic Species in Proline Catalysis?HELVETICA CHIMICA ACTA, Issue 3 2007Experiments Pointing to an Alternative View, Thoughts Abstract The N,O-acetal and N,O-ketal derivatives (oxazolidinones) formed from proline, and aldehydes or ketones are well-known today, and they are detectable in reaction mixtures involving proline catalysis, where they have been considered ,parasitic dead ends'. We disclose results of experiments performed in the early 1970's, and we describe more recent findings about the isolation, characterization, and reactions of the oxazolidinone derived from proline and cyclohexanone. This oxazolidinone reacts (THF, room temperature) with the electrophiles , -nitrostyrene and chloral (=trichloroacetaldehyde), to give the Michael and aldol adduct, respectively, after aqueous workup (Scheme,5). The reactions occur even at ,75° when catalyzed with bases such as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) or EtN(i-Pr)2 (DIPEA) (10%; Table,1). It is shown by NMR (Figs.,1 and 3) and IR analysis (Figs.,2 and 4) that the primarily detectable product (before hydrolysis) of the reaction with the nitro-olefin is again an oxazolidinone. When dissolved in hydroxylic solvents such as MeOH, ,hexafluoroisopropanol' ((CF3)2CHOH; HFIP), AcOH, CF3COOH, or in LiBr-saturated THF, the ring of the oxazolidinone from cyclohexanone and proline opens up to the corresponding iminium ion (Tables,2,4), and when treated with strong bases such as DBU (in (D8)THF) the enamino-carboxylate derived from proline and cyclohexanone is formed (Scheme,8). Thus, the two hitherto putative participants (iminium ion and enamine) of the catalytic cycle (Scheme,9) have been characterized for the first time. The commonly accepted mechanism of the stereoselective C,C- or C,X-bond-forming step (i.e., A,D) of this cycle is discussed and challenged by thoughts about an alternative model with a pivotal role of oxazolidinones in the regio- and diastereoselective formation of the intermediate enamino acid (by elimination) and in the subsequent reaction with an electrophile (by trans -addition with lactonization; Schemes,11,14). The stereochemical bias between endo - and exo -space of the bicyclo[3.3.0]octane-type oxazolidinone structure (Figs.,5 and 6) is considered to possibly be decisive for the stereochemical course of events. Finally, the remarkable consistency, with which the diastereotopic Re -face of the double bond of pyrrolidino-enamines (derived from proline) is attacked by electrophiles (Schemes,1 and 15), and the likewise consistent reversal to the Si -face with bulky (Aryl)2C-substituents on the pyrrolidine ring (Scheme,16) are discussed by invoking stereoelectronic assistance from the lone pair of pyramidalized enamine N-atoms. [source] Synthesis of Lanthanide(III) Chelates by Using ,Click' ChemistryHELVETICA CHIMICA ACTA, Issue 3 2007Janne Ketola Abstract The copper(I)-catalyzed dipolar [2+3] cycloaddition reaction of an azide and a terminal alkyne is exploited in the preparation of various europium(III), terbium(III), and dysprosium(III) chelates (Schemes,1,3). By changing the nature of the alkyne and the azide, a wide range of chelates and biomolecule-labeling reactants were obtained. The photophysical properties (Table) of the synthesized chelates are also discussed. [source] A Novel Synthesis of Highly Substituted Perhydropyrrolizines, Perhydroindolizines, and Pyrrolidines: Inhibition of the Peptidyl-Prolyl cis/trans Isomerase (PPIase) Pin1HELVETICA CHIMICA ACTA, Issue 2 2007Romain Siegrist Abstract In this paper, we describe the synthesis and biological evaluation of highly substituted perhydropyrrolizines that inhibit the peptidyl-prolyl cis/trans isomerase (PPIase) Pin1, an oncogenic target. The enzyme selectively catalyzes the cis/trans isomerization of peptide bonds between a phosphorylated serine or threonine, and proline, thereby inducing a conformational change. Such structural modifications play an important role in many cellular events, such as cell-cycle progression, transcriptional regulation, RNA processing, as well as cell proliferation and differentiation. Based on computer modeling (Fig.,2), the new perhydropyrrolizinone derivatives (,)- 1a,b, decorated with two substituents, were selected and synthesized (Schemes,1,3). While enzymatic assays showed no biological activity, 15N,1H-HSQC-NMR spectroscopy revealed that (,)- 1a,b bind to the WW recognition domain of Pin1, apparently in a mode that does not inhibit PPIase activity. To enforce complexation into the larger active site rather than into the tighter WW domain of Pin1 and to enhance the overall binding affinity, we designed a perhydropyrrolizine scaffold substituted with additional aromatic residues (Fig.,5). A novel, straightforward synthesis towards this class of compounds was developed (Schemes,4 and 5), and the racemic compounds (±)- 22a,22d were found to inhibit Pin1 with Ki values (Ki,=,inhibition constant) in the micromolar range (Table,2). To further enhance the potency of these inhibitors, the optically pure ligands (+)- 22a and (+)- 33b,c were prepared (Schemes,6 and 7) and shown to inhibit Pin1 with Ki values down to the single-digit micromolar range. According to 15N,1H-HSQC-NMR spectroscopy and enzymatic activity assays, binding occurs at both the WW domain and the active site of Pin1. Furthermore, the new synthetic protocol towards perhydropyrrolizines was extended to the preparation of highly substituted perhydroindolizine ((±)- 43; Scheme,8) and pyrrolidine ((±)- 48a,b; Scheme,9) derivatives, illustrating a new, potentially general access to these highly substituted heterocycles. [source] Practical Stereo- and Regioselective, Copper(I)-Promoted Strecker Synthesis of Sugar-Modified ,,, -Unsaturated IminesHELVETICA CHIMICA ACTA, Issue 3 2006Guobin Zhou Abstract The regio- and stereoselective, Lewis acid catalyzed Strecker reaction between Me3SiCN and different aldimines incorporating a 2,3,4,6-tetrakis- O -pivaloyl- D -glucopyranosyl (Piv4Glc) chiral auxiliary has been worked out. Depending on the conditions used, high yields (up to 95%) and good diastereoselectivities (de >,86%) were achieved under mild conditions (Table,1), especially with CuBr,,,Me2S as catalyst. Our protocol allows the ready preparation of asymmetric ,,, -unsaturated , -amino acids such as (R)-2-amino-4-phenylbut-3-enoic acid (13; Scheme,2) and congeners thereof. [source] Internal Nucleophilic Termination in Acid-Mediated Polyene Cyclizations Part 4,HELVETICA CHIMICA ACTA, Issue 12 2005Synthetic Access to Tetracyclic Didehydro, Tetradehydro Analogues of (±)- Ambrox® Treatment of the unsaturated bicyclic homoallylic alcohols (E)- and (Z)- 5 and (Z)- and (E)- 10 and allenic alcohol 16 with an excess of ClSO3H in 2-nitropropane or CH2Cl2 at ,,80° afforded, in moderate yields (ca. 30,70%), diastereoisomer mixtures of racemic tetracyclic ethers 12a,c (Table,1) and 17a,b (Table,2), respectively. These kinetically controlled stereospecific transformations are believed to proceed via concerted or nonconcerted pathways (see Schemes,4 and 6) and the results are fully consistent with our earlier work. Representing novel didehydro bridged analogues of known, olfactively active labdane tricyclic ethers, the organoleptic properties of 12a,c and 17a,b are briefly described, especially those of 12c which, in the context of structure,activity studies, is a racemic didehydro analogue of the known ambergris odorant Ambrox®. [source] Modulation of the Lifetime of Water Bound to Lanthanide Metal Ions in Complexes with Ligands Derived from 1,4,7,10-Tetraazacyclododecane Tetraacetate (DOTA)HELVETICA CHIMICA ACTA, Issue 5 2005Shanrong Zhang A series of di- and tetraamide derivatives of DOTA were synthesized, and their lanthanide(III) complexes were examined by multinuclear 1H-, 13C-, and 17O-NMR spectroscopy, and compared with literature data of similar, known complexes (Table). All ligands formed structures similar to the parent [LnIII(DOTA)], complexes, with four N-atoms and four O-atoms from DOTA and one O-atom from the inner-sphere water molecules. Interestingly, the lifetimes ,M of the inner-sphere, metal-bound water molecules vary widely, ranging from nano- to milliseconds, depending on the identity of the pendent amide side chains. In general, positively charged [LnIII(DOTA-tetraamide)]3+ complexes display the longest residence times (high ,M values), while complexes with additional charged functional groups on the extended amides display much smaller ,M values, even when the side groups are not directly coordinated to the central Ln3+ ions. The design of novel [LnIII(DOTA-tetraamide)]3+ complexes with a wide, tunable range of ,M values is of prime importance for the application of fast-responding, paramagnetic chemical-exchange-saturation-transfer (PARACEST) imaging agents used for the study of physiological and metabolic processes. [source] Synthesis and Photochemical Evaluation of Iodinated Squarylium Cyanine DyesHELVETICA CHIMICA ACTA, Issue 5 2005Paulo Several (multiply) iodinated squarylium cyanine dyes of type 1 and 8 (see Scheme and Table), derived from 1,3-benzothiazole and 6-iodo-1,3-benzothiazole, were synthesized as potential new photosensitizers, with absorptions in the 700-nm region. Their ability to generate singlet oxygen (1O2) was assessed by luminescence-decay measurement in the near-IR. Some of these new dyes show interesting photophysical properties, and may be potentially used in photodynamic therapy (PDT). [source] Second-Generation Inhibitors for the Metalloprotease Neprilysin Based on Bicyclic Heteroaromatic Scaffolds: Synthesis, Biological Activity, and X-Ray Crystal-Structure AnalysisHELVETICA CHIMICA ACTA, Issue 4 2005Stefan Sahli A new class of nonpeptidic inhibitors of the ZnII -dependent metalloprotease neprilysin with IC50 values in the nanomolar activity range (0.034,0.30,,M) were developed based on structure-based de novo design (Figs.,1 and 2). The inhibitors feature benzimidazole and imidazo[4,5- c]pyridine moieties as central scaffolds to undergo H-bonding to Asn542 and Arg717 and to engage in favorable , - , stacking interactions with the imidazole ring of His711. The platform is decorated with a thiol vector to coordinate to the ZnII ion and an aryl residue to occupy the hydrophobic S1, pocket, but lack a substituent for binding in the S2, pocket, which remains closed by the side chains of Phe106 and Arg110 when not occupied. The enantioselective syntheses of the active compounds (+)- 1, (+)- 2, (+)- 25, and (+)- 26 were accomplished using Evans auxiliaries (Schemes,2, 4, and 5). The inhibitors (+)- 2 and (+)- 26 with an imidazo[4,5- c]pyridine core are ca. 8 times more active than those with a benzimidazole core ((+)- 1 and (+)- 25) (Table,1). The predicted binding mode was established by X-ray analysis of the complex of neprilysin with (+)- 2 at 2.25-Å resolution (Fig.,4 and Table,2). The ligand coordinates with its sulfanyl residue to the ZnII ion, and the benzyl residue occupies the S1, pocket. The 1H -imidazole moiety of the central scaffold forms the required H-bonds to the side chains of Asn542 and Arg717. The heterobicyclic platform additionally undergoes ,-, stacking with the side chain of His711 as well as edge-to-face-type interactions with the side chain of Trp693. According to the X-ray analysis, the substantial advantage in biological activity of the imidazo-pyridine inhibitors over the benzimidazole ligands arises from favorable interactions of the pyridine N-atom in the former with the side chain of Arg102. Unexpectedly, replacement of the phenyl group pointing into the deep S1, pocket by a biphenyl group does not enhance the binding affinity for this class of inhibitors. [source] Synthesis of N -Substituted (3S,4S)- and (3R,4R)-Pyrrolidine-3,4-diols: Search for New Glycosidase InhibitorsHELVETICA CHIMICA ACTA, Issue 12 2004Robert N -Substituted (3S,4S)- and (3R,4R)-pyrrolidine-3,4-diols 9 and 10, respectively, were derived from (+)- L - and (,)- D -tartaric acid, respectively. Compounds 9k, 9l, and 9m with the N -substituents, BnNH(CH2)2, 4-PhC6H4CH2NH(CH2)2 and 4-ClC6H4CH2NH(CH2)2, respectively, showed modest inhibitory activities toward , - D -amyloglucosidases from Aspergillus niger and from Rhizopus mold (Table,1). Unexpectedly, several (3R,4R)-pyrrolidine-3,4-diols 10 showed inhibitory activities toward , - D -mannosidases from almonds and from jack bean (Table,3). N -Substitution by the NH2(CH2)2 group, i.e., 10g, led to the highest potency. [source] Synthesis of Novel Chiral Ionic Liquids and Their Phase Behavior in Mixtures with Smectic and Nematic Liquid CrystalsHELVETICA CHIMICA ACTA, Issue 11 2004Martin Tosoni Alkylation of 1-alkyl-1H -imidazoles 2a,f with citronellyl bromide 1b opens access to chiral 1H -imidazolium bromides 3a,f (Scheme,1). A similar strategy yielded the chiral pyridinium ionic liquid 6 (Scheme,2). Dialkylation of 1H -imidazole (7) gave the C2 -symmetric 1,3-dicitronellyl-1H -imidazolium bromide (8) (Scheme,3). Differential scanning calorimetry and optical polarizing microscopy revealed smectic mesophases for 1-citronellyl-3-tetradecy-1H -limidazolium bromide (3e) and 1-citronellylpyridinium bromide (6) (Table). In binary mixtures with smectic and nematic liquid crystals 9 and 10, 1-citronellyl-3-methyl-1H -imidazolium bromide (3a) behaved differently. Increasing quantities of 3a cause a decrease of the smectic-phase width for the mixture 3a/9 (Fig.,3), whereas the phase width of the nematic phase for 3a/10 remained nearly constant (Fig.,4). [source] | ||||||||||||||||||||||||||||||||||