bluuebunny/crossref_metadata_2025_split huggingface dataset:
Highlights of PET studies on chiral radiotracers and drugs at Brookhaven
Authors: Ding Yu‐Shin , Fowler Joanna S. 
Published: June 2003

AbstractWe review several PET studies of chiral molecules which have been carried out in our laboratory. In many cases the enantiomers behave differently, reflecting factors such as differential specificity for enzymes and transporters and binding to plasma proteins, as well as selective binding to receptors. These studies demonstrate that PET imaging is a suitable method to investigate the behavior of a chiral drug in the human body and is a powerful tool in drug development. It is important to emphasize the essential and pivotal role that organic synthesis has played in the development of PET during the last quarter century. PET is now an important tool in the neurosciences, cardiology, and oncology and is available in hundreds of institutions worldwide. However, PET is by no means mature in terms of the study of chiral drugs; hundreds of racemic drugs have been developed but only a few have been labeled with positron emitters to study their stereoselectivity. One reason is the complexity of rapid synthesis, including chiral synthesis and chiral purification. New developments in these areas are needed. Although PET is a challenging and expensive technology, it is exquisitely suited to functional and neurochemical studies of the human brain and other organs. Its use in drug research and development holds promise in understanding duration of action and stereoselectivity of drugs and in facilitating drug discovery and the introduction of new drugs into the practice of medicine. Drug Dev. Res. 59:227–239, 2003. © 2003 Wiley‐Liss, Inc.
Development of a GABAergic treatment for substance abuse using PET
Authors: Gerasimov M.R. , Dewey S.L. 
Published: June 2003

AbstractDevelopment of an effective treatment for substance abuse relies on a better understanding of the nature of the brain reward circuitry and neurotransmitter systems regulating the mechanisms responsible for drug abuse, addiction, and dependence. The use of positron emission tomography (PET) enables the direct assessment of pharmacokinetic and pharmacodynamic events in vivo. We demonstrated that administration of gamma‐vinyl gamma aminobutyric acid (GVG, vigabatrin), acting through potentiation of GABAergic tone, leads to decreases in brain extracellular dopamine concentrations as measured with PET and in vivo microdialysis. This knowledge, combined with the notion that addictive drugs share the ability to stimulate dopaminergic neurotransmission, suggests a novel GABAergic strategy for the treatment of substance abuse. Over the past several years PET and in vivo microdialysis, combined with an array of behavioral tests, have demonstrated the potential utility of this approach. Taken together, our data support the use of vigabatrin for the treatment of multiple drug addictions. Drug Dev. Res. 59:240–248, 2003. © 2003 Wiley‐Liss, Inc.
Positron‐labeled DOPA analogs to image dopamine terminals
Authors: DeJesus Onofre T. 
Published: June 2003

AbstractAltered dopamine function has been implicated in disorders such as Parkinson's disease (PD) and other motor disorders, schizophrenia, substance abuse, attention deficit disorder, and other neuropsychiatric diseases. A useful approach to the development of PET imaging agents for dopamine terminals is to target the enzymes involved in dopamine biosynthesis. Tyrosine hydroxylase (TH) converts dietary L‐p‐tyrosine to L‐3,4‐dihydroxyphenylalanine (L‐DOPA), which is the first and rate‐limiting step in dopamine synthesis. Thus, a TH‐targeted imaging agent would be the ideal PET tracer of dopamine neuronal activity. However, efforts to develop TH‐based tracers have so far been unsuccessful. The next enzyme in dopamine synthesis is aromatic L‐amino acid decarboxylase (AAAD), which converts L‐DOPA to dopamine. AAAD was the first target in the development of imaging agents for dopamine neurons. The first useful AAAD PET tracer was 6‐[18F]Fluoro‐L‐DOPA (FDOPA). Later, a practicable synthesis of L‐[β‐11C]DOPA was developed. However, the adherence of these tracers to all the catabolic pathways of L‐DOPA has been a disadvantage because of the contributions of labeled metabolites to PET images. Thus, alternative tracers with simpler metabolism such as fluoro‐L‐m‐tyrosine (FMT) have been developed. PET studies in nonhuman primates have suggested that FMT is the PET imaging agent of choice for AAAD‐containing neurons. Initial human studies show that this marker is useful in the assessment of AAAD‐related neuropsychiatric disorders. This article discusses the origins and validation of dopamine PET tracers and delineates the similarities and differences between therapeutic drug development and radiopharmaceutical development as exemplified by studies on the dopamine system. Drug Dev. Res. 59:249–260, 2003. © 2003 Wiley‐Liss, Inc.
Labeled antibiotics: Positron tomography as a tool for measuring tissue distribution
Authors: Tewson T.J. 
Published: June 2003

AbstractThe literature covering the work involved in preparing and using antibiotics labeled with short‐lived positron‐emitting radionuclides is reviewed. The short half‐lives of these radionuclides, in the range of 20–110 min, requires the development of special labeling methods and also limits the time scale of studies that can be performed. However, in spite of these limitations a number of different labeled antibiotics have been studied in humans and, utilizing positron tomography, the tissue concentrations of the compounds and how they change with respect to time have been measured. Conventional radiopharmaceuticals for imaging infection are also briefly discussed, together with the potential of FDG/PET for drug development in this area. Drug Dev. Res. 59:261–268, 2003. © 2003 Wiley‐Liss, Inc.
Analysis of long‐term profitability and DSM needs of utilities in a partially liberalized retail market by a generation system expansion model
Authors: Takahashi Masahito , Asano Hiroshi 
Published: June 2003

AbstractRetail competition in the electric power market was introduced in Japan in March 2000. Although the liberalization is limited to a part of the retail power market having about 30% of the total electricity demand, the liberalized customer segment is now subject to competition among the utilities and new entrants. This paper examines the profitability of competitive pricing for eligible segmented customers through a scenario‐based model analysis focusing on the demand characteristics of segmented customers. The model includes the utility's investment in power generation for segmented customers, considering long‐term rather than short‐term profitability. Load leveling is not always achieved under profit‐maximizing behavior of the utility because the profitability of competitive pricing depends on load patterns of bypassed customers and price differentials among power suppliers. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 144(4): 43–52, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10111
Influence of gap length on the gas‐puff z‐pinch plasma produced by an inductive pulsed power system
Authors: Imasaka Kiminobu , Takahashi Kazuki , Suehiro Junya , Hara Masanori 
Published: June 2003

AbstractIn this study, an argon gas‐puff z‐pinch plasma was produced by an inductive pulsed power system. The gap length dependence of plasma characteristics such as the pinch plasma behavior, soft x‐ray emissions, and spatial distribution of hot spots, was investigated. The soft x‐ray output decreased with gap length, and hot spots generated by sausage instability were distributed along the z‐axis for shorter delay times of the discharge onset. However, hot spots were distributed in the center of the gap space with increased delay times, regardless of the gap length, and the number of hot spots decreased. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 144(4): 1–8, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10126
Self‐tuning of fuzzy rules when learning data have a radically changing distribution
Authors: Gonda Eikou , Miyata Hitoshi , Ohkita Masaaki 
Published: June 2003

AbstractIn this paper, we propose a new type of membership functions (MSFs) and their efficient use to improve optimization of fuzzy reasoning using a steepest descent method. In self‐tuning of fuzzy rules using the steepest descent method, an algorithm to avoid suboptimal solutions by modifying learning coefficients has been proposed, where piecewise linear MSFs were introduced. In such an algorithm, when learning data have a radically changing distribution, it is impossible to avoid suboptimal solutions.To overcome this problem, we propose to apply double right triangular MSFs to the self‐tuning of fuzzy reasoning. By using these MSFs, radically changing grades can be represented easily. In addition, by a technique of simulated annealing (SA) we propose to move the peak positions of the MSFs according to the progress of learning so as to arrange the MSFs in certain positions where the learning data are changing radically. Compared with the algorithm using piecewise linear MSFs, this new algorithm makes it possible to avoid suboptimal solutions more effectively. The advantages of this new technique are demonstrated by numerical examples involving function approximations. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 144(4): 63–74, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10168
Nonlinear separation modeling and control of a boiler system by use of actual data of a thermal power plant
Authors: Nakamura Masatoshi , Yoshikai Taisuke , Goto Satoru , Matsumura Shiro 
Published: June 2003

AbstractConstruction of a reasonable controller and automatic determination of the BIR for a boiler system in a thermal power plant are investigated based on the nonlinear separation control method by using actual data of the thermal power plant. Nonlinear separation control consists of nonlinear static compensation and linear dynamics compensation, applied independently. The effectiveness of the proposed method is verified by numerical simulation studies. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 144(4): 53–62, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10179
New Methods for the Preparation of Aromatic Aldehydes
Authors: Kantlehner Willi 
Published: July 2003

AbstractThis review aims to provide an overview of the use of oligoformylamine derivatives and related compounds as formylating reagents for aromatic compounds. The synthesis of aromatic aldehydes by means of Fries rearrangement of aryl formates is also reported on. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Chondrochloren A and B, New β‐Amino Styrenes fromChondromyces crocatus(Myxobacteria)
Authors: Jansen Rolf , Kunze Brigitte , Reichenbach Hans , Höfle Gerhard 
Published: July 2003

AbstractIn a screening for biologically active metabolites of the genusChondromyces, two novel metabolites, chondrochloren A (1) and B (2), were isolated from several strains ofC. crocatus. Compounds1and2are unique chloro‐hydroxy‐styryl amides of a highly modified C14carboxylic acid, which comprises an unsaturated ketone, two hydroxy, two methoxy and three methyl groups. After assignment of the absolute configuration of both carbinol stereocenters by Mosher’s method, NMR spectroscopic data combined with MM2 calculations allowed the prediction of the preferred conformation in solution. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Glyoxylates as Versatile Building Blocks for the Synthesis of α‐Amino Acid and α‐Alkoxy Acid Derivatives via Cationic Intermediates
Authors: Meester Wim J. N. , Maarseveen Jan H. van , Schoemaker Hans E. , Hiemstra Henk , Rutjes Floris P. J. T. 
Published: July 2003

AbstractGlyoxylic acid and its derivatives are versatile ester‐substituted aldehyde equivalents that can be used efficiently to generate precursors for reactive cationic intermediates such as iminium ions, N‐acyliminium ions, N‐sulfonyliminium ions, and oxycarbenium ions. These intermediates have been extensively used for the synthesis of (cyclic) α‐amino acid and α‐alkoxyester derivatives. The research presented in this review is largely dedicated to the evaluation of the scope and limitations of glyoxylate‐derived cationic intermediates in intra‐ and intermolecular reactions with suitable nucleophiles. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Synthesis and Biological Evaluation of Imino Sugar−Oligoarabinofuranoside Hybrids, a New Class of Mycobacterial Arabinofuranosyltransferase Inhibitors
Authors: Marotte Karine , Ayad Tahar , Génisson Yves , Besra Gurdyal S. , Baltas Michel , Prandi Jacques 
Published: July 2003

AbstractThe mycobacterial cell wall is a promising target for the development of new antituberculosis drugs. We report the synthesis and preliminary biological evaluation of imino sugar−oligoarabinofuranoside hybrids, a new class of mycobacterial arabinosyltransferase inhibitors. These hybrids were built from various chiral polyhydroxylated pyrrolidines (imino sugars) linked to small oligoarabinofuranosides. The coupling reaction was a reductive amination of a suitable oligoarabinofuranoside aldehyde with an unprotected amine counterpart. Good in vitro arabinosyl transferase inhibitions were observed for some of these hybrids with radioactive [14C]‐DPA as the glycosyl donor and, more importantly, their inhibitory activity was modulated by the length of the oligosaccharide moiety. This result shows that potential inhibitors of these mycobacterial enzymes can be prepared by linking them to an acceptor‐like oligoarabinofuranoside. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Computer‐Aided Molecular Design of Hydrogen Bond Equivalents of Nucleobases: Theoretical Study of Substituent Effects on the Hydrogen Bond Energies of Nucleobase Pairs
Authors: Kawahara Shun‐ichi , Uchimaru Tadafumi 
Published: July 2003

AbstractSubstituent effects on the hydrogen bond energies of Watson−Crick‐type base pairs, formed between a chemically modified nucleic acid base derivative and an unmodified one, were evaluated by ab initio molecular orbital theory. Different trends were observed in the relationship between the substituent and the hydrogen bond energy in each base pair. The predicted hydrogen bond energies correlated well with the experimentally measured binding properties, and so ab initio calculation appears to be an effective method with which to estimate the stabilities of base pairs between chemically modified nucleic acid bases. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Regio‐ and Diastereoselectivity in 1,3‐Dipolar Cycloaddition Reactions of 2‐Phenylisatogen and Its 3‐Phenylimino Derivative with Electron‐Deficient Alkenes
Authors: Astolfi Paola , Bruni Paolo , Greci Lucedio , Stipa Pierluigi , Righi Lara , Rizzoli Corrado 
Published: July 2003

AbstractThe 1,3‐dipolar cycloadditions of the cyclic nitrones 2‐phenyl‐3H‐indole‐3‐one N‐oxide (2‐phenylisatogen, 1a) and 2‐phenyl‐3‐phenylimino‐3H‐indole N‐oxide (1b) to several electron‐deficient alkenes 2a−d are reported. All the reactions studied are highly diastereoselective: the regioisomers with the ethoxycarbonyl group attached to the 4‐position of the isoxazolidine moiety are the only products isolated, except in the reactions of nitrones 1a and 1b with ethyl acrylate 2a where mixtures of the two different regioisomers are obtained. Crystal structures of compounds 3b, 5a, 5b, 9a and 10b were determined by X‐ray analysis, while the structure of the other cycloadducts was determined by spectroscopic analysis. Ab initio calculations were carried out showing that product distribution may be influenced by kinetic rather than thermochemical factors. Ab initio calculations of the 1H NMR shielding tensor were performed on compounds 3b, 4b, 5a and 6b and the chemical shifts obtained are in perfect agreement with the experimental ones. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Stereoselective Synthesis of Fully Protected (S)‐1,7‐Dioxaspiro[5,5]undec‐4‐ene Derivatives of Sugars
Authors: Caputo Romualdo , Ciriello Umberto , Festa Pasquale , Guaragna Annalisa , Palumbo Giovanni , Pedatella Silvana 
Published: July 2003

AbstractPerbenzylated 1,7‐dioxaspiro[5,5]undec‐4‐ene derivatives of sugars are obtained in three steps, starting from fully protected glycono‐1,5‐lactones. The procedure is based on the attack of a lithiated dithiinyl reagent (6) on the starting δ‐glyconolactone. The C‐glycosidation leads to the sole thermodynamically more stable α‐hemiacetal derivative, the spirocyclization of which is then accomplished with BF3·Et2O. The fully protected unsaturated spiroacetals can be smoothly desulfurized for the purpose of any further elaborations of the free double bond. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Domino Aza‐Claisen/Mannich Cyclization Reaction from a Chiral α‐Alkoxy Enamine or Sequential Alkylation of an α‐Alkoxy Ester Enolate or Nitrile Anion, Followed by an Intramolecular Wittig Reaction: Two (3+2) Annulation Routes to Homochiral 4‐Alkyl‐4‐hydroxy‐2‐cyclopentenone Synthesis
Authors: Kuhn Cyrille , Skaltsounis Leandros , Monneret Claude , Florent Jean‐Claude 
Published: July 2003

AbstractA study on the enantioselective synthesis of 4‐alkyl‐4‐hydroxyalkylidene‐cyclopentenone prostaglandins is reported. Two (3+2) annulation processes allow the synthesis of homochiral 4‐alkyl‐4‐hydroxy‐2‐cyclopentenones 4−5, 10−11, and 17. The first process involves a domino aza‐Claisen/Mannich cyclization reaction, resulting from the alkylation of an α‐alkoxy‐enamine, derived from chiral α‐alkoxy aldehydes 1, 9, or 16 with 3‐iodo‐2‐(methoxymethoxy)prop‐1‐ene (3) as the acetonyl equivalent. The second process is based on the sequential alkylation of esters 21, 39, or nitrile 20 with acetonyl equivalents 3 or 25, followed by an intramolecular Wittig reaction. As an application, the synthesis of the naturally occurring alkylidene‐cyclopentenone prostaglandin clavulone II from the spiro[cyclopentene‐furan]one 5 and the formal total synthesis of (+/‐)‐untenone 19 has been carried out. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Synthesis of Methyl (R)‐2‐O‐Propargylglycerate, a Precursor to Analogues of the 2‐O‐Alkylglycerate Part of the Moenomycins
Authors: Mansourova Madina , Rohr Katja , Hennig Lothar , Findeisen Matthias , Oehme Ramona , Giesa Sabine , Welzel Peter 
Published: July 2003

AbstractConditions allowing optically active methyl glycerate to be converted, without racemization, into the 2‐O‐propargyl derivative, via the 2‐O‐allyl derivative, are reported. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Synthesis and Characterization of Soluble Octaaryl‐ and Octaaryloxy‐Substituted Metal‐Naphthalocyanines
Authors: Vagin Sergei , Hanack Michael 
Published: July 2003

AbstractAn easy route for the synthesis of vanadium, zinc, magnesium, etc. complexes of new soluble symmetrical octa(m‐trifluoromethylphenyl) or octa(m‐trifluoromethylphenoxy) substituted 2,3‐naphthalocyanines {[(m‐CF3Ph)8NcM] or [(m‐CF3PhO)8NcM]} in good yields is described in detail. The structures of the synthesized compounds were verified by UV/Vis and 1H and 13C NMR spectroscopy, as well as by mass spectrometry. The good solubilities of the prepared compounds in toluene and coordinating solvents (e.g., THF), was explained in terms of the nonplanar arrangements of eight m‐CF3Ph substituents in relation to the Nc macrocycle, preventing aggregation of the molecules. The Q‐bands in the UV/Vis spectra of the [(m‐CF3Ph)8NcM] species are each bathochromically shifted by ca. 13 nm in relation to [(m‐CF3PhO)8NcM] species, appearing at 817 nm for [(m‐CF3Ph)8NcVO] in toluene. All NcMs prepared exhibit very high molar extinction coefficients for the Q‐band {lg(ϵ) ≈︁ 5.6} in THF. Some of prepared Nc complexes appeared to be very unstable on exposure to daylight. In addition, a nickel‐catalyzed Kumada cross‐coupling synthesis of substituted o‐terphenyls, intermediate compounds for the preparation of octaaryl‐substituted Ncs, is described. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Redoxactive Oligonucleotides: Synthesis and Properties of Flavocoenzyme‐DNA
Authors: Mees Alexandra , Behrens Christoph , Schwögler Anja , Ober Matthias , Carell Thomas 
Published: July 2003

AbstractThe flavin heterocycle is the key component in the important and ubiquitous FMN and FAD coenzymes. As such, the flavin is able to catalyse oxygen‐transfer reactions in many monooxygenases, as well as one‐ and two‐electron transfer processes. We recently inserted the flavin heterocycle into oligonucleotides with the future goal of creating flavindependent ribozymes with redox‐catalytic properties. We showed that a flavin inside duplex DNA is able to exchange electrons with its environment. These electron‐exchange capabilities strongly modulate the fluorescence properties of the flavin heterocycle in DNA. Herein we report a detailed study of how DNA single and double strands change the fluorescence intensity of the flavin cofactor. In agreement with the assumption that the flavin photooxidises predominately guanine and adenine bases, we observe the strongest fluorescence quenching when the flavin is in close contact with one of these purine nucleobases. No fluorescence quenching is observed in the presence of pyrimidine bases. We conclude that A and G in a DNA environment have a similar effect as Trp and Tyr in a protein surrounding, regarding the fluorescence properties of the flavin coenzyme. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
[6]Radialenes Revisited
Authors: Höpfner Thomas , Jones Peter G. , Ahrens Birte , Dix Ina , Ernst Ludger , Hopf Henning 
Published: July 2003

Abstract[6]Radialene (2d) and its hexa‐ (2a) and dodecamethyl (2c) derivatives were subjected to several novel chemical reactions. Pyrolysis of2aunder flash vacuum conditions provided a mixture of 1,5‐hydrogen shift products9and10, and the benzocyclobutenes5and6, produced by electrocyclization of an intermediateo‐xylylene derivative7. At the higher end of the investigated temperature range (200−400 °C) the formation of cyclization products11was also observed. The hydrocarbon2cisomerized to the benzocyclobutene12under these conditions. Photolysis at 254 nm converted2cinto a novel isomer that, according to X‐ray structural analysis, has the unusual twist configuration14. Compound2cwas photoisomerized through photoinduced hydrogen shift reactions to15, and the stablep‐xylylenes16and17. Dichloro‐ and dibromocarbene add to2dwith formation of the rotaradialeneantiadducts19aand19b, respectively, the structures of which were also established by X‐ray structural analysis. With dichlorocarbene,2aprovided the three dichlorocarbene adducts20,22, and23, whereas methylenation with diiodomethane/trimethylaluminium afforded a complex product mixture from which the monoadduct21could be isolated. The analogous product24and the bisadduct25were obtained from2cunder the same conditions. Epoxidation of2awithm‐chloroperbenzoic acid gave the monoadduct26, together with higher epoxidation products, which, however, could not be separated. Depending on the reaction conditions,2ccould be oxidized withm‐chloroperbenzoic acid to give the epoxides27,28, and29. Hydrochlorination of2agave a complex mixture of addition products, which was converted into the olefins9and10by base treatment, showing that the addition step takes place less regioselectively than previously assumed. With Fe2(CO)9,2awas converted into the iron tricarbonyl complex33in poor yield. Repetition of the literature procedure for the preparation of2aallowed the isolation of novel diastereomers of this oldest hexaradialene; according to NMR experiments the methyl substituents of this hydrocarbon are arranged as shown in the structurecccaca‐2a.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)