bluuebunny/crossref_metadata_2025_split huggingface dataset:
Refining pharmacogenetic research in schizophrenia: Control for patient‐related variables
Authors: Lane Hsien‐Yuan , Chang Yue‐Cune , Huang Chieh‐Liang , Chang Wen‐Ho 
Published: September 2003

AbstractThere is strong evidence to suggest that genetic variation plays an important role in inter‐individual differences in medication response and toxicity. Most of the previous pharmacogenetic studies, however, cannot be reconfirmed. Of note, drug efficacy or side effects depend not only on genetic factors but also on nongenetic factors, such as illness duration, past treatment history, and drug dosage or blood concentration. However, most pharmacogeneticists did not consider or control the possible impact of the nongenetic factors. Schizophrenia is a severe neuropsychiatric disorder with a polygenic mode of inheritance that is also governed by nongenetic factors. Schizophrenia's symptoms are principally subdivided into two subtypes, positive and negative. The positive symptoms include delusions and hallucinations; the negative symptoms, blunted affect and social withdrawal. Atypical antipsychotics are usually superior in the treatment of negative symptoms than typical agents. Although atypical agents are becoming the mainstay for schizophrenia treatment, what makes an antipsychotic “atypical” remains unclear. One of our recent studies have simultaneously evaluated the effects of genetic and nongenetic determinants on the efficacy of risperidone (a widely used atypical antipsychotic agent). We found that 5‐HT2A receptor 102‐T/C polymorphism could predict clinical response (mainly for negative symptoms rather than positive symptoms) in schizophrenia. Among nongenetic factors, fewer previous hospitalizations and higher risperidone dosage also predicted better treatment response after control for the 102‐T/C polymorphism and other confounders. It is hoped that this novel study model could revolutionize future research in pharmacogenetics or other fields of genetics. Drug Dev. Res. 60:164–171, 2003. © 2003 Wiley‐Liss, Inc.
Chemistry of Sulfonate‐ and Sulfonamide‐Stabilized Carbanions − The CSIC Reactions
Authors: Postel Denis , Van Nhien Albert Nguyen , Marco José L. 
Published: September 2003

AbstractIn this account we review the varied, but extensively documented reactions affording acyclic alkanesulfonates, alkanesulfonamides, and heterocyclic ring systems (sultones, 1,2‐oxathiole S,S‐dioxides, sultams, and 2,3‐dihydroisothiazole S,S‐dioxides) from conveniently functionalized alkanesulfonates or alkanesulfonamides, by a general procedure that we have named and classified as CSIC reactions both as intermolecular [Carbanion‐mediated Sulfonate (or Sulfonamide) Intermolecular Coupling] and as intramolecular [Carbanion‐mediated Sulfonate (or Sulfonamide) Intramolecular Cyclization] variants of the conversion. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Conception, Characterization and Correlation of New Marine Odorants
Authors: Kraft Philip , Eichenberger Walter 
Published: September 2003

AbstractVia a synthetic sequence consisting of PPA‐mediated Friedel−Crafts acylation of veratrol (8), Clemmensen reduction, demethylation with TMSI, Williamson ether synthesis employing 3‐chloro‐2‐(chloromethyl)prop‐1‐ene and in‐situ ruthenium tetroxide oxidation, numerous substituted benzo[b][1,4]dioxepinones 15−27 and 2,3‐dihydro‐1H‐5,9‐dioxacyclohepta[f]indenones 7, 13 and 14 were prepared to study their odor−structure correlation. In the course of these studies, we discovered the extremely powerful new marine odorant 7‐(3′‐methylbutyl)benzo[b][1,4]dioxepin‐3‐one (16). On the basis of the measured odor threshold data, an olfactophore model was constructed that rationalizes the observed odor intensities, and indicates an aliphatic hydrophobe at a distance of 6.3 Å from the centre of the aromatic‐ring binding site. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Recent Advances in the Total Synthesis of Piperidine and Pyrrolidine Natural Alkaloids with Ring‐Closing Metathesis as a Key Step
Authors: Felpin François‐Xavier , Lebreton Jacques 
Published: September 2003

AbstractThis microreview focuses on recent applications of the ring‐closing metathesis reaction (RCM) to construct piperidine and pyrrolidine cores for the total synthesis of natural alkaloids. The most recent examples are described, from simple piperidine alkaloids to complex pentacyclic structures such as (+)‐tabersonine. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Unusual Stabilization of 1,2‐Diamino Derivatives of Quincorine and Quincoridine by Carbon Dioxide: Persistent Crystalline prim‐Ammonium‐Carbamate Salts and Their Reactivity towards Isatoic Acid Anhydride
Authors: Neda Ion , Kaukorat Thomas , Fischer Axel K. 
Published: September 2003

AbstractThe reaction of N‐methylisatoic anhydride 1 with a series of quincorine (QCI) and quincoridine (QCD) derivatives furnished the corresponding QCI‐ and QCD‐substituted anthranilic acid amides 4−9. In the synthesis of 4−9, we investigated the influence of the C5 substituent of 2‐aminomethyl derivatives of QCI and QCD on their basicity and polarity and, therefore, on their reactivity towards isatoic acid anhydride. By exposing a number of 2‐aminomethyl derivatives of QCI and QCD to (carbon dioxide from) air, the formation of carbon dioxide adducts 10−15 was observed. In an unusual reaction, we obtained the first set of chiral ammonium carbamates derived from primary amines, which provides a convenient method for purifying and stabilizing aminomethyl derivatives of QCI and QCD. All compounds were fully characterized by spectroscopic methods. In addition, the structure of 11 was proved by X‐ray crystal structure determination. The heterocyclic nitrogen atoms display trigonal‐pyramidal coordination geometries; the amido group is essentially planar. N‐2′ of the ammonium ion is a triple hydrogen bond donor to the carboxylato oxygen atoms of three different carbamate anions. The resulting net effect is a hydrophilic plane parallel to the ab plane. The crystal packing involves six classical hydrogen bonds. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Reinvestigation into the Synthesis of Oligonucleotides Containing 5‐(β‐D‐Glucopyranosyloxymethyl)‐2′‐deoxyuridine
Authors: Turner John J. , Meeuwenoord Nico J. , Rood Anita , Borst Piet , van der Marel Gijs A. , van Boom Jacques H. 
Published: September 2003

AbstractA reinvestigation into the synthesis of oligonucleotides containing 5‐(β‐D‐glucopyranosyloxymethyl)‐2′‐deoxyuridine revealed that existing procedures for the preparation of these DNA fragments suffered from decomposition at the final deprotection step. The decomposition product was identified as the corresponding 5‐(aminomethyl)‐2′deoxyuridyl derivative arising from amino substitution of the β‐D‐glucosyl moiety during ammonolysis. This was shown to be suppressed by the use of phosphoramidite 21 in place of 12 for solid‐phase oligonucleotide synthesis, in conjunction with short ammonia treatment at room temperature. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Tele vs. Oxidative Substitution of Hydrogen in meta Monochloromethyl, Dichloromethyl, and Trichloromethyl Nitrobenzenes in the Reaction with Grignard Reagents
Authors: Mąkosza Mieczysław , Varvounis George , Surowiec Marek , Giannopoulo Thomas 
Published: September 2003

AbstractGrignard reagents add to nitrobenzene derivatives containing trichloromethyl, dichloromethyl, and monochloromethyl groups in the meta position to form σH adducts, which are either further converted through departure of a chloride anion, giving products of tele substitution, or oxidized to products of oxidative nucleophilic substitution of hydrogen. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Side‐Chain Retention During Lithiation of 4‐Picoline and 3,4‐Lutidine: Easy Access to Molecular Diversity in Pyridine Series
Authors: Kaminski Thomas , Gros Philippe , Fort Yves 
Published: September 2003

AbstractThe first direct ring‐selective lithiation of 4‐picoline and 3,4‐lutidine has been achieved through the use of BuLi/LiDMAE aggregates to prevent the usual side‐chain metallation. Several functionalities have been introduced at the C‐2, C‐6 and C‐5 positions by ring‐selective sequential lithiation, opening a simple and fast route to polysubstituted pyridine building blocks. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Condensation Reaction Between α‐Amino Acid Phenylhydrazides and Carbonyl Compounds
Authors: Verardo Giancarlo , Geatti Paola , Martinuzzi Paolo , Merli Marcello , Toniutti Nicoletta 
Published: September 2003

AbstractThe natural α‐amino acid phenylhydrazides 1a−d readily react with the aldehydes 2a−d and ketones 2e−h to produce the 3‐(phenylamino)imidazolidin‐4‐one derivatives 4 in good yields. Their structures were confirmed by X‐ray structural analysis. Polycyclic systems were obtained from the reaction of L‐tryptophan phenylhydrazide (1d) and L‐histidine phenylhydrazide (1e) with benzaldehyde (2c), which gave 1,10‐diphenyl‐2‐(phenylamino)‐2,9,10a‐triazacyclopenta[b]fluoren‐3‐one (5dc) and 4,6‐diphenyl‐7‐(phenylamino)‐3,4,6,7,8a,9‐hexahydro‐8H‐diimidazo[1,5‐a:4′,5′‐d]pyridin‐8‐one (5ec), respectively. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
NMR and X‐ray Crystallographic Analysis of Thermodynamically Stable Tetraphenylporphyrin‐Stoppered Rotaxanes
Authors: Ikeda Taichi , Asakawa Masumi , Goto Midori , Nagawa Yoshinobu , Shimizu Toshimi 
Published: September 2003

AbstractTetraphenylporphyrin‐stoppered rotaxanes, in which tetraphenylporphyrin rhodium(III) chloride serves for end‐capping of the thread molecule through axial coordination, were prepared from the inclusion complexes formed between crown ether and secondary ammonium cation derivatives. Two types of the thread molecules, with different molecular lengths, were used for the rotaxane preparation. The obtained porphyrin‐stoppered rotaxanes proved to be thermodynamically stable in their pure forms at room temperature. 1H NMR measurements indicated that the protons of the thread molecule and the crown ether are considerably affected by the shielding effect of the terminal porphyrin. We confirmed that the intensity of the shielding effect is applicable as a probe for estimation of the location of the crown ether. We found different chemical shifts for individual members of pairs of methylene protons on the same crown ether carbon when the relatively shorter thread molecule was used, whereas we observed similar chemical shifts for those in the rotaxane with longer thread molecule. This result indicates that the stronger shielding effect of the porphyrin exposes the two faces of the crown ether to different magnetic environments in the case of the relatively shorter thread molecule. X‐ray crystallography for the porphyrin‐stoppered rotaxane with the relatively shorter thread molecule revealed that the crown ether forms many hydrogen bonds with the thread molecule. We confirmed that not only the hydrogen atoms of the secondary ammonium ion and the neighboring methylene groups, but also the β‐hydrogen atoms of the axially coordinated pyridine moiety participate in hydrogen bond formation with the crown ether oxygen atoms. It is likely that the catechol rings of the crown ether interact with the phenyl groups of the terminal porphyrin. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Sulfene−Pyridine Adducts: Lewis Acid/Base Complexes, Ylides, Pyridinium Sulfinate Zwitterions, or Carbene Ylide/SO2 Complexes?
Authors: Bucher Götz 
Published: September 2003

AbstractThe reactions between a number of sulfenes and pyridine have been investigated by both density functional and ab initio theory. Two reaction channels were found. Addition of pyridine to the sulfene S atom produces products with the character of Lewis acid/base adducts. In polar solvents such as acetonitrile, scipcm calculations predict a shortening of the S−N bond with increasing ylide character, as revealed by long‐wavelength absorptions predicted by time‐dependent DFT calculations. Addition of pyridine to the sulfene C atom affords adducts better described as Lewis acid/base adducts between carbene pyridine ylides and SO2 rather than as pyridinium sulfinate zwitterions. Again, scipcm calculations predict tighter binding in polar solvents. In the series of sulfene‐pyridine adducts investigated, the C‐bound adduct was consistently lower in energy than the S‐bound adduct, by at least 15 kcal/mol. For the formation of the C‐bound adducts an activation enthalpy of 14 kcal/mol or larger is calculated, while the formation of S‐bound sulfene−pyridine adducts is predicted to proceed without any barrier. The S‐bound adducts are therefore formed in kinetically controlled reactions, while the C‐bound adducts are the thermodynamically favored products. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Bismuth Triflate: An Efficient Catalyst for the Formation and Deprotection of Tetrahydropyranyl Ethers
Authors: Stephens Jacqueline R. , Butler Phillip L. , Clow Curtis H. , Oswald Matthew C. , Smith Russell C. , Mohan Ram S. 
Published: September 2003

AbstractThe tetrahydropyranylation of alcohols under solvent‐free conditions is efficiently catalyzed by bismuth triflate (0.1 mol %). The experimental procedure is simple and works well with a variety of alcohols and phenols. The catalyst is insensitive to air and small amounts of moisture, easy to handle and relatively nontoxic. The deprotection of THP ethers is also catalyzed by bismuth triflate (1.0 mol %). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Functionalization of [60]Fullerene and of [60]Fullerene Monoadducts by Photochemical Cycloaddition of 4‐Methyl‐1,2,4‐triazoline‐3,5‐dione
Authors: Ulmer Lars , Siedschlag Christina , Mattay Jochen 
Published: September 2003

AbstractThe photoreactions of 4‐methyl‐1,2,4‐triazoline‐3,5‐dione (NMTAD) with C60 and with several fullerene derivatives have been studied. In general, NMTAD cycloadds to C60 and to its monoadducts with closed structures in a highly regioselective [2+2] fashion at a cis‐1 [6,6] double bond. Cycloadditions to azafulleroids occur by a slightly different pathway and result in partially cluster‐opened bis(adducts). 1,6‐Methano[60]fulleroid, however, also undergoes a [2+2+2] cycloaddition in the absence of light. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
First Isolation of Thione‐Propiolic Acid Adducts − Synthesis of Thiodioxenones
Authors: Okuma Kentaro , Maekawa Shinobu , Shibata Shinji , Shioji Kosei , Inoue Thoru , Kurisaki Tsutomu , Wakita Hisanobu , Yokomori Yoshinobu 
Published: September 2003

AbstractTreatment of adamantane‐2‐thione (1a) with propiolic acid (2a) afforded a novel type of cycloadduct, spiro[adamantane‐2,2′‐[1,3]oxathiin]‐6‐one (3a), in quantitative yield. The reaction proceeds through a concerted process, as was confirmed by kinetic analysis. Treatment of 1a with butynoic acid or phenylpropiolic acid gave the corresponding adducts regioselectively. Interestingly, only one isomer was obtained by treatment of thiofenchone with propiolic acid, suggesting that the reaction proceeded stereospecifically. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Quantitative Four‐State Conformational Analysis by Ring Current NMR Anisotropy: A Family of Molecules Capable of Intramolecular π‐Stacking
Authors: Chen Jing , Cammers‐Goodwin Arthur 
Published: September 2003

AbstractA novel, multi‐state, conformational analysis based on the magnetic anisotropy of molecules undergoing fast dynamic exchange is described. Calculated chemical shift tensors combined with experimental data from proton NMR studies were used to quantify conformational distributions as a function of solvent and temperature for a hydrocarbon and two fluorocarbon derivatives of N,N′‐[1,3‐phenylenebis(methylene)]bis(2‐phenylpyridinium) dibromide. Inspection for adequate analyses involved confirming that the mathematical expressions conserved magnetization (mass). Enthalpic parameters from VT‐NMR gave some indication of the nature of the impact of solvent on conformation. Results indicated that electrostatic interactions between aromatic rings can strongly impact organic conformation in solution. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Enantioselective Strecker Reactions between Aldimines and Trimethylsilyl Cyanide Promoted by Chiral N,N′‐Dioxides
Authors: Jiao Zhigang , Feng Xiaoming , Liu Bo , Chen Fuxue , Zhang Guolin , Jiang Yaozhong 
Published: September 2003

AbstractAxially chiral N,N′‐dioxide Lewis base promoters have been developed and have for the first time been applied to the asymmetric synthesis of α‐amino nitriles through cyanide addition to aldimines. The chiral 3,3′‐dimethyl‐2,2′‐biquinoline N,N′‐dioxide 2 exhibited high enantioselectivity for asymmetric Strecker reactions between N‐benzhydrylimines and trimethylsilyl cyanide. In the presence of 1 equiv. of chiral promoter 2, the cyanosilylation of aldimines afforded the corresponding α‐amino nitriles with ee values of up to 95%. Optically pure products (99% ee) were obtained simply by recrystallization in the cases of some of the products. Moreover, the promoter 2 could be recovered and reused at least four times without any loss of enantioselectivity and reactivity. A putative mechanism for the enantioselective Strecker reactions is also discussed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
The Combination of TsNH2 and NCS as Nitrogen and Chlorine Sources for Direct Diamination of Enones
Authors: Timmons Cody , Chen Dianjun , Xu Xin , Li Guigen 
Published: September 2003

AbstractThe regio‐, stereo‐, and chemoselective diamination of enones has been achieved without the observation of any haloamines. The reaction employs the readily available inexpensive combination of NCS and TsNH2 as an electrophilic nitrogen source, and three nitriles as nucleophilic nitrogen sources. A novel mechanism involving the formation of aziridinium intermediates from the reaction of TsNHCl with olefins and a new [2+3] cyclic addition for aziridinim ring opening has been proposed for the electrophilic diamination of olefins. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
New 4′‐Functionalized 2,2′:6′,2′′‐Terpyridines for Applications in Macromolecular Chemistry and Nanoscience
Authors: Andres Philip R. , Lunkwitz Ralph , Pabst Gunther R. , Böhn Karlheinz , Wouters Daan , Schmatloch Stefan , Schubert Ulrich S. 
Published: September 2003

AbstractThe well‐known reaction of 4′‐chloro‐2,2′:6′,2′′‐terpyridine with alkoxide nucleophiles leads to 4′‐functionalized 2,2′:6′,2′′‐terpyridines. This reaction allows the easy introduction of different functional groups onto the terpyridine at the 4′‐position, i.e. opposite to the metal binding site, in one reaction step. Among the functionalized 2,2′:6′,2′′‐terpyridines reported here are amines (including chiral examples), carboxylic acids, simple alkoxy‐chain terpyridines with different chain lengths, and a stilbene‐functionalized terpyridine. Moreover, the synthesis of two important already known substances was significantly improved. One example of a sequential functionalization of the (aminopentoxy)terpyridine with a dithiolane functionality is also reported. For two of the alkyl‐chain‐functionalized terpyridines, single‐crystal X‐ray crystallographic data were obtained. Finally, ordered monolayers of alkyl‐substituted terpyridines on HOPG were visualized using STM. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Regio‐ and Stereoselective Dirhodium(II)‐Catalysed Intramolecular C−H Insertion Reactions of α‐Diazo‐α‐(dialkoxyphosphoryl)acetamides and ‐acetates
Authors: Gois Pedro M. P. , Afonso Carlos A. M. 
Published: September 2003

Abstractα‐Diazo‐α‐(dialkoxyphosphoryl)acetates and ‐acetamides afforded α‐(dialkoxyphosphoryl)lactones and lactams, respectively, in moderate to high yields through dirhodium(II)‐catalysed intramolecular carbon−hydrogen insertion reactions. In the case of α‐diazo‐α‐(dialkoxyphosphoryl)acetamides a remarkable preference for the formation of γ‐lactam was observed, with stereocontrol in favour of the trans diastereomer. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Acidity of Substituted Benzenes − An Ab Initio Study of the Influence of Methoxy, Trifluoromethyl and Trifluoromethoxy Groups by a Novel Trichotomy Formula
Authors: Kovačević Borislav , Maksić Zvonimir B. , Primorac Miljenko 
Published: September 2003

AbstractThe acidities of mono‐ and polysubstituted benzenes incorporating one, two, or three OCH3, OCF3, or CF3 groups were investigated by use of reliable ab initio theoretical models. The calculated deprotonation energies are in very good agreement with available experimental data, although these are unfortunately sparse. A recently developed novel trichotomy formula proved useful for interpretation of predicted variation in acidity in the monosubstituted compounds. In particular, the long‐range final state effect in OCF3 and CF3 derivatives is confirmed. It is reflected in the stabilization of the lone‐pair electrons formed upon deprotonation at the meta and para positions. The theoretically established long‐range influence of OCF3 and CF3 substituents is in accordance with empirical knowledge obtained by experimental chemical reactivity studies. The acidities of multiply substituted benzenes exhibit additivity properties based on the ISA (independent substituent approximation) model established earlier. It is conclusively shown that the combination of the additivity rule and the trichotomy formula offers a powerful tool for interpretation of the acidity of polysubstituted benzenes and of other multiply substituted aromatics, thus shedding new light on this very old and important problem. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Cover Picture: Conception, Characterization and Correlation of New Marine Odorants (Eur. J. Org. Chem. 19/2003)
Authors: Kraft Philip , Eichenberger Walter 
Published: September 2003

AbstractThe cover picture shows, in front of a water surface and with an electon‐density cloud in the form of a water droplet, the best marine odorant of a series of substituted benzo[b][1,4]dioxepinones and 2,3‐dihydro‐1H‐5,9‐dioxacyclohepta[f]indenones. It posseses a very intense and diffusive, marine odor with floral‐aldehydic nuances and an exceptionally low odor threshold of 0.014 ng/L air! A beam highlights the hydrophobic binding centre 6.3 Å apart from the aromatic ring binding site. This feature accounts for its exceptional odor characteristics as was rationalized by an olfactophore model constructed on the basis of 20 measured odor thresholds. A synthetic sequence consisting of PPA‐mediated Friedel−Crafts acylation, Clemmensen reduction, demethylation, Williamson ether synthesis employing 1‐chloro‐2‐(chloromethyl)prop‐1‐ene and subsequent ruthenium tetroxide oxidation opens up a simple, straightforward access to these marine odorants and related structures. Details are discussed in the article by P. Kraft and W. Eichenberger on p. 3735 ff.