bluuebunny/crossref_metadata_2025 huggingface dataset:
Gadolinium, a mechano‐sensitive channel blocker, inhibits osmosis‐initiated motility of sea‐ and freshwater fish sperm, but does not affect human or ascidian sperm motility
Authors: Krasznai Zoltán , Morisawa Masaaki , Krasznai Zoárd Tibor , Morisawa Sachiko , Inaba Kazuo , Bazsáné Zsuzsa Kassai , Rubovszky Bálint , Bodnár Béla , Borsos Antal , Márián Teréz
Published: July 2003

Exposure to hypo‐osmotic or hyperosmotic environment triggers the initiation of fish sperm motility. In this article, we report that calcium and potassium channel blockers do not influence motility of puffer fish sperm but calmodulin antagonists reversibly decrease it, suggesting that calmodulin–Ca2+ interactions are prerequisite for the initiation of sperm motility in this species. Gadolinium (a stretch activated ion channel blocker) decreased the motility of puffer fish sperm from 92 ± 3% to 6 ± 3% and that of carp sperm from 91 ± 7% to 3.5 ± 4.3% in a dose‐dependent manner (10–40 μM). The effect of gadolinium was reversible, suggesting that stretch activated ion channels participate in the initiation of sperm motility of the two species. Gadolinium inhibits changes in the isoelectric point of certain proteins of puffer fish sperm, which occur when sperm motility is initiated in a hypertonic solution. Anisotropy measurements showed that hypo‐osmotic treatment, which initiates carp sperm motility, increased membrane fluidity. When hypo‐osmotic treatment was given in the presence of gadolinium, the sperm membrane remained as rigid as in quiescent cells, while motility was blocked. By contrast, gadolinium did not influence the motility parameters of Ciona or human sperm. Based on these lines of evidence, we suggest that conformational changes of mechanosensitive membrane proteins are involved in osmolality‐dependent but not osmolality‐independent sperm. Cell Motil. Cytoskeleton 55:232–243, 2003. © 2003 Wiley‐Liss, Inc.
Direct, dynamic assessment of cell‐matrix interactions inside fibrillar collagen lattices
Authors: Petroll W. Matthew , Ma Lisha
Published: July 2003

Cell mechanical behavior has traditionally been studied using 2‐D planar elastic substrates. The goal of this study was to directly assess cell‐matrix mechanical interactions inside more physiologic 3‐D collagen matrices. Rabbit corneal fibroblasts transfected to express GFP‐zyxin were plated at low density inside 100 μm‐thick type I collagen matrices. 3‐D datasets of isolated cells were acquired at 1–3‐min intervals for up to 5 h using fluorescent and Nomarski DIC imaging. Unlike cells on 2‐D substrates, cells inside the collagen matrices had a bipolar morphology with thin pseudopodial processes, and without lamellipodia. The organization of the collagen fibrils surrounding each cell was clearly visualized using DIC. Using time‐lapse color overlays of GFP and DIC images, displacement and/or realignment of collagen fibrils by focal adhesions could be directly visualized. During pseudopodial extension, new focal adhesions often formed in a line along collagen fibrils in front of the cell, while existing adhesions moved backward. This process generated tractional forces as indicated by the pulling in of collagen fibrils in front of the cell. Meanwhile, adhesions on both the dorsal and ventral surface of the cell body generally moved forward, resulting in contractile shortening along the pseudopodia and localized extracellular matrix (ECM) compression. Cytochalasin D induced rapid disassembly of focal adhesions, cell elongation, and ECM relaxation. This experimental model allows direct, dynamic assessment of cell‐matrix interactions inside a 3‐D fibrillar ECM. The data suggest that adhesions organize along actin‐based contractile elements that are much less complex than the network of actin filaments that mechanically links lamellar adhesions on 2‐D substrates. Cell Motil. Cytoskeleton 55:254–264, 2003. © 2003 Wiley‐Liss, Inc.
Gliding movement in Peranema trichophorum is powered by flagellar surface motility
Authors: Saito Akira , Suetomo Yasutaka , Arikawa Mikihiko , Omura Gen , Mostafa Kamal Khan S.M. , Kakuta Soichiro , Suzaki Etsuko , Kataoka Katsuko , Suzaki Toshinobu
Published: July 2003

A colorless euglenoid flagellate Peranema trichophorum shows unique unidirectional gliding cell locomotion on the substratum at velocities up to 30 μm/s by an as yet unexplained mechanism. In this study, we found that (1) treatment with NiCl2 inhibited flagellar beating without any effect on gliding movement; (2) water currents applied to a gliding cell from opposite sides caused detachment of the cell body from the substratum. With only the anterior flagellum adhering to the substratum, gliding movement continued along the direction of the anterior flagellum; (3) gentle pipetting induced flagellar severance into various lengths. In these cells, gliding velocity was proportional to the flagellar length; and (4) Polystyrene beads were translocated along the surface of the anterior flagellum. All of these results indicate that a cell surface motility system is present on the anterior flagellum, which is responsible for cell gliding in P. trichophorum. Cell Motil. Cytoskeleton 55:244–253, 2003. © 2003 Wiley‐Liss, Inc.
Cyclooxygenase and cAMP‐dependent protein kinase reorganize the actin cytoskeleton for motility in HeLa cells
Authors: Glenn Honor L. , Jacobson Bruce S.
Published: July 2003

The adhesion of a cell to its surrounding matrix is a key determinant in many aspects of cell behavior. Adhesion consists of distinct stages : attachment, cell spreading, motility, and/or immobilization. Interrelated signaling pathways regulate these stages, and many adhesion‐related signals control the architecture of the cytoskeleton. The various cytoskeletal organizations then give rise to the specific stages of adhesion. It has been shown that arachidonic acid acts at a signaling branch point during cell attachment. Arachidonic acid is metabolized via lipoxygenase to activate actin polymerization and cell spreading. It is also metabolized by cyclooxygenase to generate small actin bundles. We have used confocal microscopy and indirect immunofluorescence to investigate the structure of these cyclooxygenase dependent actin bundles in HeLa cells. We have also employed cell migration assays and pharmacological modulation of cyclooxygenase and downstream signals. The results indicate that cyclooxygenase and PKA stimulate the formation of actin bundles that contain myosin II and associate with small focal adhesions. In addition, we demonstrate that this cytoskeletal organization correlates with increased cell motility. Cell Motil. Cytoskeleton 55:265–277, 2003. © 2003 Wiley‐Liss, Inc.
3‐D in vitro model of early skeletal muscle development. Cell Motil Cytoskeleton 54:226–236, 2003
Authors: Cheema U. , Yang S‐Y. , Mudera V. , Goldspink G. , Brown R.A.
Published: July 2003

The original article to which this Erratum refers was published in Cell Motility and the Cytoskeleton (2003) 54(3) 226–236
Positron emission tomography and its use to image the occupancy of drug binding sites
Authors: Gatley S. John , Volkow Nora D. , Fowler Joanna S. , Ding Yu‐Shin , Logan Jean , Wang Gene‐Jack , Gifford Andrew N.
Published: June 2003

The development of positron emission tomography (PET) and the ability to synthesize compounds labeled with the short‐lived positron emitters 11C and 18F has made possible the imaging and quantification of drug binding sites in the human body. By conducting PET studies with an appropriate radioligand before and after treatment with a drug, the fraction of the total number of binding sites that is occupied by the drug (the “occupancy” of the site) can often be determined. To the extent that occupancy is a good indicator of pharmacological activity, such PET experiments can aid the development of drug dosage regimens. Some of the general issues involved in PET studies of drug occupancy are discussed. There have been many such studies involving antipsychotic drugs and dopamine D2 receptor radioligands. Since neuroleptics have been extensively reviewed elsewhere, only the major findings are discussed here. Other binding sites (and drug classes) in the dopamine system to which this methodology has been applied include: the dopamine transporter (stimulant drugs) and monoamine oxidase A and B (antidepressant drugs). Occupancy studies are also possible for many drug targets beyond the dopamine system. Drug Dev. Res. 59:194–207, 2003. © 2003 Wiley‐Liss, Inc.
Imaging studies of biodistribution and kinetics in drug development
Authors: Berridge Marc S. , Heald Donald L. , Lee Zhenghong
Published: June 2003

Although the intravenous route of administration is rarely used for drugs, it is by far the most common route for PET and SPECT radiotracers. This article discusses the use of planar and tomographic nuclear medicine technologies to image and quantify the distribution of drugs after local administration. In principle, this would include topical dermatologic, otic, ophthalmic, rectal, and vaginal administration, as well as the intramuscular, oral, and inhalation routes, although precedents do not yet exist for all of these. The studies reviewed focus mainly on oral ingestion and oral and nasal inhalation. The use of nondrug tracers for formulations is discussed, principally with planar imaging or SPECT using radionuclides such as 99mTc, as well as PET imaging where the active ingredient of a formulation can be labeled with 11C or sometimes 18F. An example of the latter type is a study of the deposition and kinetics in the lungs and airways of triamcinolone acetonide, an antiinflammatory steroid used for topical treatment of allergic rhinitis and asthma, dispensed from an inhaler. PET has high potential for evaluation of different formulations and delivery devices in the development of topically applied drugs. Drug Dev. Res. 59:208–226, 2003. © 2003 Wiley‐Liss, Inc.
Highlights of PET studies on chiral radiotracers and drugs at Brookhaven
Authors: Ding Yu‐Shin , Fowler Joanna S.
Published: June 2003

We 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

Development 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

Altered 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

The 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

Retail 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

In 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

In 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

Construction 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

This 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

In 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

Glyoxylic 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

The 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

Substituent 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

The 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

Perbenzylated 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

A 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

Conditions 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

An 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

The 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

[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)
Synthesis of Hydroxylated and Methoxylated Polybrominated Diphenyl Ethers − Natural Products and Potential Polybrominated Diphenyl Ether Metabolites
Authors: Marsh Göran , Stenutz Roland , Bergman Åke
Published: July 2003

Hydroxylated and methoxylated polybrominated diphenyl ethers (OH‐PBDEs and MeO‐PBDEs) may be natural products or they may be formed as metabolites of polybrominated diphenyl ethers (PBDEs), frequently used as flame retardants. The aim of this work was to synthesize authentic OH‐ and MeO‐PBDE reference standards for analytical and toxicological studies. Brominated phenoxybenzaldehydes were prepared either by coupling of 2,4‐dibromophenol with various fluorobenzaldehydes or by coupling of brominated hydroxybenzaldehydes with 2,2′,4,4′‐tetrabromodiphenyliodonium chloride. OH‐PBDEs were synthesized via the brominated phenoxybenzaldehydes by Baeyer−Villiger oxidation and acid‐catalyzed hydrolysis. These OH‐PBDEs were ortho‐ and para‐brominated (relative to the hydroxy group) with benzyltrimethylammonium tribromide and/or ortho‐brominated with bromine/tert‐butylamine, and were also brominated with bromine in one case. MeO‐PBDEs were obtained by methylation of the prepared OH‐PBDEs. MeO‐PBDEs were also prepared through the coupling of brominated methoxyphenols with 2,2′,4,4′‐tetrabromodiphenyliodonium salts, the corresponding OH‐PBDEs being obtained after demethylation. A majority of the OH‐/MeO‐PBDEs prepared have the hydroxy/methoxy group in the ortho position relative to the diphenyl ether bond. All OH‐/MeO‐PBDEs prepared have 2,4‐dibromo substitution patterns (relative to the diphenyl ether bond) in the non‐hydroxy‐/non‐methoxy‐containing ring. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Diastereoselective Preparation of Silylated Pyrrolidones through Palladium‐Catalysed Cyclisations
Authors: Thorimbert Serge , Giambastiani Giuliano , Commandeur Claude , Vitale Maxime , Poli Giovanni , Malacria Max
Published: July 2003

A new palladium‐catalysed allylic alkylation affording silylated 3‐vinylpyrrolidones has been developed. The method relies upon the interaction between a stabilized acetamide enolate anion and a silicon‐containing, nitrogen‐tethered η3‐allylpalladium moiety. Two variants have been studied, involving the location of the silicon atom on either olefinic carbon atom of the cyclisation precursor. In both cases 5‐exo ring closure was the only cyclisation process observed. The stereoselectivity of these processes is discussed. These results contrast with related β‐oxo ester cyclisations, in which competitive 7‐endo mode is observed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Synthesis of Non‐Natural Amino Acids from N‐(p‐Tolylsulfonyl)‐α,β‐didehydroamino Acid Derivatives
Authors: Ferreira Paula M. T. , Maia Hernâni L. S. , Monteiro Luís S.
Published: July 2003

Carbon nucleophiles, amines, and oxygen nucleophiles were treated with the methyl ester of N‐(tert‐butoxycarbonyl)‐N‐(p‐tolylsulfonyl)‐α,β‐didehydroalanine, and also with the methyl esters of N‐(tert‐butoxycarbonyl)‐O‐(p‐tolylsulfinyl)‐α,β‐didehydroserine and N‐(tert‐butoxycarbonyl)‐β‐(1,2,4‐triazol‐1‐yl)‐α,β‐didehydroalanine, both of which were obtained from the former substrate. Carbon nucleophiles of the β‐dicarbonyl type gave furanic amino acids, which were converted into the corresponding pyrrole derivatives (dehydroprolines) in high yields, while use of amines allowed the synthesis of α,α‐diamino acids and β‐amino‐α,β‐didehydroamino acids. Different types of alkoxyamino acids were obtained by treatment of the above substrates with oxygen nucleophiles. The reactivities of the α,β‐didehydroaminobutyric and α,β‐didehydrophenylalanine analogues were also tested. Some of the methods developed were applied to the synthesis of cross‐linked amino acids, namely didehydrolanthionine and histidino‐α,β‐didehydroalanine derivatives. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Strained Aromatic Compounds: Are σ‐ and π‐Strains Additive? A Hybrid DFT Study of Dicyclobutano‐, Dicyclobutadieno‐ and Di(1,3‐methanocyclopentano)[2,2]paracyclophanes
Authors: Stanger Amnon , Ben‐Mergui Na'ama , Perl Sharon
Published: July 2003

The structures and energies of dicyclobutano[2,2]paracyclophane (1), dicyclobutadieno[2,2]paracyclophane (2) and di(1,3‐methanocyclopentano)[2,2]paracyclophane (3) were calculated at the B3LYP/6‐31G* theoretical level, in order to understand the behavior of systems that are π‐ and σ‐strained. It was found that the effect of the two types of strain on the geometry is approximately additive, and that the slight deviation found is due to specific interactions (electronic or steric) between the ethano bridges in the [2,2]paracyclophanes and the aromatic moieties or between a substituent and another aromatic moiety. It was found that 1 is ca. 3 kcal mol−1 less strained than [2,2]paracyclophane and cyclobutabenzene, 2 is ca. 6 kcal mol−1 less strained than [2,2]paracyclophane and benzocyclobutadiene, and 3 is ca. 6 kcal mol−1 more strained than [2,2]paracyclophane and 1,3‐methanoindane. These deviations from additivity are explained by the above‐mentioned interactions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Synthesis of Methoxy‐Substituted Exocyclic (E)‐ and (Z)‐Unsaturated Methyl Pyranosides and a Study of Their Reactivity towards Lewis Acids
Authors: Deleuze Aurélie , Sollogoub Matthieu , Blériot Yves , Marrot Jérôme , Sinaÿ Pierre
Published: July 2003

The first synthesis of methoxy‐substituted exocyclic (E)‐ and (Z)‐unsaturated methyl pyranosides is reported involving the syn elimination of a selenoxide derivative as a key step. The rearrangement of these exocyclic enol ethers in the presence of TIBAL and DIBAL‐H is also described. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Pyridinium‐Based Cationic Lipids as Gene‐Transfer Agents
Authors: Ilies Marc Antoniu , Seitz William A. , Caproiu Miron T. , Wentz Melissa , Garfield Robert E. , Balaban Alexandru T.
Published: July 2003

Cationic lipids are a promising alternative to viral vectors for gene therapy, allowing the delivery of larger plasmids without immunogenicity, despite their lower transfection efficiency. Among them, heterocyclic systems with imidazolium or pyridinium polar head groups have definite advantages such as the excellent transfection profiles and low cytotoxicity. Our approach for synthesizing heterocyclic cationic lipids differs from those previously described because we synthesize a pyridinium ring from simple starting materials. First a pyrylium salt is formed via diacylation of alkenes. The pyrylium salt is then converted by primary amines into pyridinium salts. Appropriate choice of the primary amine allows the attachment of two hydrophobic chains yielding compounds 21A and 25A (with various chain lengths derived from palmitic, stearic and oleic acids). The same strategy allowed the preparation of lipophilic derivatives 21B, 25B useful as strongly fluorescent markers for the study of the properties of biological membranes. Preliminary tests with some of the compounds 21A and 25A, on several cell lines, showed comparable transfection efficiencies and lower cytotoxicity than those obtained with standard commercial transfection agents. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
An Iterative Procedure for the Synthesis of Conjugated ψ‐Chlorotrienoic and ‐tetraenoic Esters and Related Derivatives
Authors: Mladenova Margarita , Tavlinova Maya , Momchev Momcho , Alami Mouâd , Ourévitch Michèle , Brion Jean Daniel
Published: July 2003

An iterative stereoselective procedure for the synthesis of isomers of conjugated ψ‐chlorotrienoic esters and ψ‐chlorotetraenoic esters as well as related conjugated ψ‐chloropolyenynoic esters is described, using readily available conjugated chlorodienol and chloroenynol derivatives as starting materials. The two‐step sequence studied is based on repetition of a one‐pot conjugated allylic alcohol oxidation/Wittig reaction followed by a reduction step. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
A Cyclopropyl‐Homoallyl Rearrangement Accompanying the Borane‐Mediated Reduction of Tosylhydrazones
Authors: Kragol Goran , Benko Iva , Muharemspahić Jasmina , Mlinarić‐Majerski Kata
Published: July 2003

The Wolff−Kishner reduction of strained cyclopropyl ketones 9‐oxo‐2,8‐didehydronoradamantane (1) and 5‐oxo‐2,4‐didehydrobrendane (5) proceeds without rearrangement, while the borane‐mediated reduction of the corresponding tosylhydrazones 1a and 5a affords the rearranged products tricyclo[4.2.1.03,8]non‐4‐ene (3) and 4‐brendene (7), respectively. Rearrangement also occurs during the reduction of the less‐strained tosylhydrazones 8a and 10a derived from cyclopropyl methyl ketone (8) and bicyclo[4.1.0]heptan‐2‐one (10). The results obtained in experiments with deuterated reagents support a concerted mechanism of diazene decomposition/cyclopropyl‐homoallyl rearrangement. This rearrangement offers a great possibility for the preparation of new polycyclic molecules and, moreover, is a convenient method for regiospecific isotopic labeling using deuterated reagents. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Palladium‐Catalyzed C−C Bond Formation: Synthesis of 1,1‐Dialkylbuta‐1,3‐dienes and β‐Phenylstyrenes via Organoboron Intermediates
Authors: Deagostino Annamaria , Prandi Cristina , Zavattaro Chiara , Venturello Paolo
Published: July 2003

α,β‐Unsaturated and α‐phenyl acetals show different reactivity when treated with LIC‐KOR superbase and trialkylboranes, in the presence of the reagent system PdL4‐ArX (Suzuki−Miyaura cross‐coupling conditions). In particular, unsaturated acetals yield gem‐dialkylbutadienes via the formation of an intermediate π‐allyl complex that facilitates an anionotropic alkyl migration; in the case of α‐phenyl derivatives, the corresponding cross‐coupling products are recovered. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Rearrangement of Germacranolides. Synthesis and Absolute Configuration of Elemane and Heliangolane Derivatives from Cnicin
Authors: Rosselli Sergio , Maggio Antonella , Raccuglia Rosa Angela , Bruno Maurizio
Published: July 2003

A study of the Cope rearrangement of 15‐oxo‐germacranolides to 15‐oxo‐elemanolides has been carried out. The synthesis of two natural elemanolides, isolated from Centaurea paui, and an efficent isomerization of the C‐4/C‐5 double bond of 15‐oxo‐germacranolides to form heliangolides are reported. The absolute configuration of all the compounds has been ascertained. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Highly Efficient Synthesis of Chloro‐ and Phenoxy‐Substituted Subphthalocyanines
Authors: Claessens Christian G. , González‐Rodríguez David , del Rey Belen , Torres Tomás , Mark Gertraud , Schuchmann Heinz‐Peter , von Sonntag Clemens , MacDonald J. Gavin , Nohr Ronald S.
Published: July 2003

A highly efficient method for the synthesis of chloro‐substituted subphthalocyanines employing a 1 M boron trichloride solution in p‐xylene is described and compared to other previously described results. The substitution reaction of the axial chlorine atom by a phenoxy group has been optimized. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
A New N,P‐Ligand with Achiralgem‐Dimethyloxazoline for Palladium(II)‐Catalyzed Cyclization of 1,6‐Enynes: Transition State Probe for theN/C transMode in Mizoroki−Heck‐Type C−C Bond Formation
Authors: Hatano Manabu , Yamanaka Masahiro , Mikami Koichi
Published: July 2003

A highly effectiveC1‐symmetricgem‐dimethyl N,P‐ligand has been developed for enantioselective palladium(II)‐catalyzed carbocyclization of 1,6‐enynes, in which theN/Ctransmode is established for the first time in the “Mizoroki−Heck‐type” transition state by virtue of theC1‐symmetric N,P‐ligand. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Dicyanocarbene and Its Isomers: A Matrix Spectroscopic Study
Authors: Maier Günther , Reisenauer Hans Peter , Ruppel Raimund
Published: July 2003

Irradiation of matrix‐isolated dicyanodiazomethane (4) with 254 nm‐light leads to the dicyanocarbene 5, which, upon further photoexcitation, undergoes successive isomerizations until a photoequilibrium between the five C3N2 isomers dicyanocarbene (T‐5), cyanoisocyanocarbene (T‐6), 3‐cyano‐2H‐azirenylidene (S‐7), 3‐isocyano‐2H‐azirenylidene (S‐8), and diisocyanocarbene (S‐9) is reached. The preferential formation of a specific member of this group can be achieved by changing the wavelength of the irradiating light. The structural elucidation of the unknown compounds 6−9 is based on a comparison of their calculated and experimental IR spectra. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Cover Picture: Synthesis and Biological Evaluation of Imino Sugar−Oligoarabinofuranoside Hybrids, a New Class of Mycobacterial Arabinofuranosyltransferase Inhibitors (Eur. J. Org. Chem. 14/2003)
Authors: Marotte Karine , Ayad Tahar , Génisson Yves , Besra Gurdyal S. , Baltas Michel , Prandi Jacques
Published: July 2003

The cover picture shows a schematic view of the expected cooperative effect of linking a potential mycobacterial arabinosyltransferase inhibitor to an acceptor‐like ligand. Important enhancement of the in vitro inhibitory porperties of various hydroxylated and fluorinated pyrrolidines was obseved when they were covalently linked to a single arabinofuranosidic unit while a longer triarabinofuranoside was deleterious for the inhibition. Details are discussed in the article by M. Baltas and J. Prandi et al. on p. 2557 ff. Photo courtesy of P. Gournon, Institut Pasteur, Paris.
Clay Modified Electrodes: Present Applications and Prospects
Authors: Navrátilová Zuzana , Kula Petr
Published: July 2003

This review presents the preparation and use of clay modified electrodes with emphasis on analytical applications. Besides, some investigations on ion‐exchange and sorption mechanisms are outlined. Expected prospects of clay modified electrodes in the field of electrochemistry are discussed briefly.