bluuebunny/crossref_metadata_2025_split huggingface dataset:
A convenient method for the synthesis of six‐membered heterocyclic enaminones
Authors: Puebla Pilar , Honores Zoila , Medarde Manuel , Caballero Esther , Feliciano Arturo San , Morán Lourdes 
Published: May 2009

AbstractEnaminones are widely employed in the synthesis of heterocycles, however heterocyclic enaminones and their use in the synthesis of more complex systems have been less studied. The reaction between 4‐chloroacetylacetate and aliphatic or aromatic 1,2‐aminoalcohols, 1,2‐aminothiols or 1,2‐diamines, yields in one pot a six‐membered 1,4‐heterocyclic system containing the enaminone moiety.
A new efficient route to 3‐vinylthiophene
Authors: Nicolas Maël , Fabre Bruno , Pilard Jean‐François , Simonet Jacques 
Published: May 2009

AbstractThe synthesis of 3‐vinylthiophene was efficiently achieved in two steps. 3‐(2‐bromoethyl)thiophene prepared from 3‐(2‐ethanol)thiophene was converted to the title compound (70% overall yield) using tetraglyme as a solvent and 1,8‐diazabicyclo[5.4.0]undec‐7‐ene as a base.
Characterization of a trace by‐product of the synthesis of the protease inhibitor tipranavir (PNU‐140690)
Authors: Martin Gary E. , Robins Russell H. , Crow Frank W. , Duholke Wayne K. , Guido Jane E. , Hadden Chad E. , Kaluzny Brian D. , Thamann Thomas J. , Pearlman Bruce A. 
Published: May 2009

AbstractTipranavirTM (PNU‐140690) is a protease inhibitor under clinical investigation for the treatment of human acquired immunodeficiency syndrome (AIDS). During scale‐up synthesis of clinical quantities of the bulk drug, a colored, transient by‐product of the final coupling reaction was observed. Quantities of this colored, transient chemical species were too low (<<0.1%) for characterization by conventional spectroscopic methods. It was, however, possible to isolate sufficient material for characterization based on mass spectrometry and submicro inverse‐detection gradient (SMIDG) nmr methods by methanol stripping of silica gel that had been used in purification of bulk drug. This process afforded an enriched feedstock from which small quantities of this highly colored and unstable (halflife < 18 hours in methanol and < 10 minutes in acetone) trace contaminant could be isolated by semi preparative reversed phase hplc. The impurity was identified as an unstable Zincke salt formed by the condensation of two molecules of the anilino precursor and the pyridine used as a base in the final step of the synthetic process. Following identification of this impurity, efforts were undertaken to engineer it out of the synthetic process.
Intermediates for the synthesis of indole alkaloids. Synthesis of tetrahydrocarbazole derivatives
Authors: Ergün Y. , Bayraktar N. , Patir S. , Okay G. 
Published: May 2009

AbstractThe synthesis of new precursors 8 and 15 for the synthesis of tetracyclic indole alkaloids were described. Many new intermediates 4‐7 and 9‐14 have also been synthesized.
Synthesis and nuclear magnetic resonance spectroscopic studies of 1‐arylpyrroles
Authors: Lee Chang Kiu , Jun Jung Ho , Yu Ji Sook 
Published: May 2009

AbstractA series of m‐ and p‐substituted 1‐phenyl, 1‐benzyl, 1‐benzoyl, and 1‐(2‐phenylethyl)pyrroles was prepared and their 1H and 13C nmr spectroscopic characteristics were examined. In general, good correlations were observed between the chemical shift values of the βH and the βC of pyrroles [except 1‐(2‐phenylethyl)pyrroles] and the Hammettt σ. The observation may be explained in terms of the electronic effects of the substituents which are transmitted through bonds and through space by interaction of the p orbitals between βCs of the pyrrole ring and m‐ and pCs of the phenyl ring. Substituent constants of 1‐pyrrolyl, 1‐pyrrolylmethyl, and 1‐pyrroloyl groups for the 1H and 13C chemical shifts of phenyl ring are also presented.
Synthesis of thiophene/phenylene co‐oligomers. I. Phenyl‐capped oligothiophenes
Authors: Hotta S. , Lee S. A. , Tamaki T. 
Published: May 2009

AbstractWe report the synthesis of phenyl‐capped oligothiophenes via improved synthetic schemes. These schemes are based on the Grignard coupling reaction and enable us to obtain the target compounds at high yields. The resulting materials have been fully characterized through nmr and ir spectroscopies. The ir analysis is particularly useful in characterizing the materials of higher molecular weight, since those materials are difficult to dissolve in organic solvent. We also show an improvement on preparation of halogenated (oligo)thiophenes that are used as intermediates for synthesizing the target compounds. An alternative synthetic route to the phenyl‐capped oligothiophenes that utilizes the Suzuki coupling reaction is presented as well.
Synthetic approaches to 3‐substituted‐5′‐(N‐pyridiniummethyl)‐4′,5′‐dihydropsoralen
Authors: Jabin Ivan , Heindel Ned D. , Rapp Robert D. , Laskin Jeffrey D. 
Published: May 2009

AbstractNew synthetic approaches to 3‐substituted‐5′‐(N‐pyridiniummethyl)‐4′,5′‐dihydropsoralens are described. The novel pathways presented utilize appropriately substituted coumarins and 4′,5′‐dihydropsoralens. The compounds proposed represent potential therapeutic agents for psoralen uv radiation treatment.
Synthesis and conversion of 2‐(pyrazol‐1‐yl)quinoxaline 4‐oxides
Authors: Kim Ho Sik , Kwag Sam Tag , Choi Kyung Ok , Okamoto Yoshihisa , Kajiwara Shinnosuke , Fujiwara Noriko , Kurasawa Yoshihisa 
Published: May 2009

AbstractThe reaction of 6‐chloro‐2‐hydrazinoquinoxaline 4‐oxide 1b with acetylacetone or benzoylacetone gave 6‐chloro‐2‐(3,5‐dimethylpyrazol‐i‐yl)quinoxaline 4‐oxide 5a or 6‐chloro‐2‐(3‐methyl‐5‐phenylpyrazol‐1‐yl)quinoxaline 4‐oxide 5b, respXectively. Compound 5a or 5b was converted into the pyrrolo[1,5‐a]quinoxaline 6a or 6b, triazolo[4,3‐a]quinoxaline 9a or 9b, and tetrazolo[1,5‐a]quinoxaline 10.
Perhydro‐1,3‐diazepine‐2,4‐diones by cyclization of 4‐ureidobutyric acids with thionyl chloride: A reinvestigation
Authors: Heckendorn Roland , Winkler Tammo 
Published: May 2009

AbstractThe structures of the previously reported aryl‐perhydro‐1,3‐diazepine‐2,4‐diones are shown to be pyrro‐lidinone carboxamide derivatives by nmr spectroscopy.
Nucleophilic substitution studies on nitroimidazoles, and applications to the synthesis of biologically active compounds
Authors: Chauvière Gérard , Viodé Cécile , Périé Jacques 
Published: May 2009

AbstractThe rationalization of the synthesis of substituted analogs of megazol, a biologically active 5‐nitroimidazole at position 4 of the imidazole ring, had led to the study of intermediate steps. The methylation by diazomethane of 2,4‐(5)dihalogeno‐5‐(4)nitroimidazole is regioselective leading to 2,4‐dihalogeno‐1‐methyl‐5‐nitroimidazole 2. On this compound 2, hard nucleophiles such as cyanide, methoxide or hydride anions react only with the halogen at the 2 position; whereas soft nucleophiles such as amine, thiol or trifluoromethyl anion from an organocopper species react only with the halogen at postion 4 in the intermediate 3b or compound 4b.
A new synthetic entry to 3‐carboxamido‐4‐carboxylic acid derivatives of isoxazole and pyrazole
Authors: Vicentini Chiara B. , Mazzanti Manuela , Morelli Carlo F. , Manfrini Maurizio 
Published: May 2009

AbstractEthyl 2‐amino‐3‐methoxycarbonyl‐4‐oxo‐2‐pentenoate (3) reacts with hydroxylamine or hydrazines to give isoxazole and pyrazole ortho‐dicarboxylic acid esters 4 and 5, respectively. Partial hydrolysis of diesters 4 and 5 afforded the corresponding dicarboxylic acid monoesters 6 and 7. Amidation of the intermediate acid chlorides 8,9 followed by hydrolysis of 4‐methylesters 10, 11 gave the title compounds 1 and 2, respectively.
Since 1995 the new chemistry of multicomponent reactions and their libraries, including their heterocyclic chemistry
Authors: Ugi Ivar , Domling Alexander , Werner Birgit 
Published: May 2009

AbstractA growing number of products, including many heterocycles, can be prepared by the one‐pot MultiComponent Reactions (MCRs) just by mixing three or more educts, and in many cases practically quantitative yields of pure products can be obtained. The 3CR by α‐aminoalkylations of nucleophiles began in the middle of the last century, and the syntheses of heterocycles by MCRs of three and four components were introduced by Hantzsch in the 1880s. The MCRs of the isocyanides with four and more educts began in 1959, and their compound libraries were mentioned since 1961. However, only since 1995 the often automated one‐pot chemistry of the MCR of the isocyanides is used extensively. If a chemical compound can be prepared by a sequence of two component reactions or a suitable MCR, the latter is always a superior procedure. The U‐4CR can be combined with other chemical reactions and MCRs as one‐pot reactions of n > 4 components, and such unions even have a much greater variety of structurally and stereochemically different products. The educts and products of Ugi‐type MCRs are more variable than those of all previous chemical reactions and other MCRs. Due to the progress in screening and automation processes in the last few years, many new compounds have been formed and investigated more rapidly than ever before. The search for new desirable products can be accomplished more than 10,000 times faster than by the older conventional methods. The now popular chemistry of the MCRs of the isocyanides fills the since long empty part of organic chemistry.
Study of the reactivity of α‐acylenaminoketones. Synthesis of pyrazoles
Authors: Negri Giuseppina , Kascheres Concetta 
Published: May 2009

AbstractThe reactions of 4‐(methylamino)‐3‐penten‐2‐one with diazoketones yielded the α‐acylenaminoketones 1–3 in good yields. Preparation of the α‐acylenaminoketone 4 was carried out by treatment of 4‐(t‐butyl‐amino)‐3‐penten‐2‐one with benzoyl chloride being followed by reaction of transamination with methyl‐amine. The reactions were carried out in five different solvents and were submitted to gas chromatogra‐phy/mass spectrometry analysis, with the goal of obtaining substituted pyrazoles and determining which of the carbonyls would preferentially be attacked by the nucleophile. The reactions of compounds 1–4 with hydrazine reagents led to the formation of the pyrazoles 5–7a‐q. Small amounts of 4‐methylamino‐2‐pentenones 10a‐q, amides 11a‐q and pyrazoles 12a‐q were also obtained in these reactions. The unexpected formation of pyrazoles 15d,h,q was detected when methanol and N,N‐dimethylformamide were used as solvents in the reactions of α‐acylenaminoketone 4 with hydrazine reagents.
Solvent‐ and concentration‐sensitive fluorescence of 2‐(3,4,5,6‐tetrafluoro‐2‐hydroxyphenyl)benzoxazole
Authors: Tanaka Kiyoshi , Deguchi Makoto , Yamaguchi Satoru , Yamada Kouji , Iwata Satoru 
Published: May 2009

Abstract2‐(3,4,5,6‐Tetrafluoro‐2‐hydroxyphenyl)benzoxazole (2) emits the long wavelength fluorescence around 500 nm in nonpolar solvent via the intramolecular proton transfer process in the excited state of 2 (enol‐form) and also emits the intermediate wavelength fluorescence around 440 nm in polar solvent, which is assumed to originate from the excited state of 2 (anion). The ease of formation of 2 (anion), compared to 2‐(2‐hydroxyphenyl)benzoxazole (1), is explained by the strongly inductive fluorine atoms. In a solvent with the intermediate polarity, 2 emits both fluorescences and their relative intensity is dependent on the concentration of 2, which is supposed to be caused by the high sensitivity of the intermediate wavelength emission to the concentration quenching.
Free radical 4‐nitrophenylation of thieno[2,3‐b]pyridine. Part 2: Isolation and structural studies of three samples of mono (4‐nitrophenyl) products; relative yields of the five possible isomers
Authors: Klemm Leroy H. , Weakley Timothy J. R. , Gilbertson Robert D. 
Published: May 2009

AbstractFrom the crude mixtures of isomeric 4‐nitrophenylthieno[2,3‐b]pyridines (3) previously reported [1] were isolated three analytically pure samples, viz. the 2‐isomer (yellow needles, mp 258°, 3a), the 6‐isomer (red prisms, mp 182°, 3e), and a ternary mixture of the 2‐, 3‐, and 4‐isomers (orange needles, mp 213°, 3a:3b:3c = 1.3:1.0:0.5). The 258° compound was identified as either 3a or 3b by its 1H nmr spectrum and definitively as the former by its x‐ray crystallographic analysis. The isomeric identities of the 182° and 213° samples were established from their 1H nmr spectra only. No 5‐isomer (3d) was identified. Semi‐quantitatively, relative isomeric yields fit the pattern 2‐ (64%)>>6‐ (14%)≥3‐ (12%)>4‐ (6%)≥5‐(≤4%). Crystallographic data for 3a are presented.
Armed‐azacrown ethers having dual binding sites in a side arm: Complexing abilities and crystal structure of two alkali‐metal complexes
Authors: Habata Yoichi , Saeki Tomomi , Akabori Sadatoshi , Zhang Xian X. , Bradshaw Jerald S. 
Published: May 2009

AbstractNew armed‐monoaza‐12‐crown‐4 and armed‐monoaza‐15‐crown‐5 ethers having dual phenolic OH and pyridine nitrogen binding sites in a side arm were prepared by the Mannich reaction of N‐methoxymethyl‐monoazacrown ethers with 3‐hydroxypyridine. Complexation studies of these new hydroxypyridine‐armed ligands were carried out by liquid membrane transport, 1H nmr titration experiments, thermodynamic values (log K, ΔH and TΔS), and X‐ray crystallography of two alkali‐metal complexes. These results indicate that the oxygen atom of the phenolic OH group and pyridine nitrogen atom of the side arm are involved in complexation under basic and neutral conditions, respectively.
Intermuscular adipose tissue (IMAT): Association with other adipose tissue compartments and insulin sensitivity
Authors: Boettcher Michael , Machann Jürgen , Stefan Norbert , Thamer Claus , Häring Hans‐Ulrich , Claussen Claus D. , Fritsche Andreas , Schick Fritz 
Published: May 2009

AbstractPurposeTo quantify intermuscular adipose tissue (IMAT) of the lower leg as well as to investigate associations with other adipose tissue (AT) compartments. The relationship between IMAT and insulin sensitivity was also examined.Materials and MethodsStandardized quantification of IMAT was performed in a large cohort (N = 249) at increased risk for type 2 diabetes in the right calf by T1‐weighted fast spin‐echo imaging at 1.5T (Magnetom Sonata; Siemens Healthcare). Additionally, whole‐body AT distribution was assessed. Insulin sensitivity was determined by glucose clamp.ResultsMales showed significantly more IMAT than females (2.1 ± 1.1 cm2 vs. 1.5 ± 0.9 cm2; P < 0.001). IMAT correlated well with other AT depots, especially with visceral AT (VAT; rfemales = 0.52, P < 0.0001 vs. rmales = 0.42, P < 0.0001). Moreover, IMAT showed a negative correlation with the glucose infusion rate (GIR; rfemales = −0.43, P = 0.0002 vs. rmales = −0.40, P = 0.0007).ConclusionQuantification of IMAT is possible by standard MR techniques. AT distribution of the lower leg is comparable to the visceral compartment with males having higher IMAT/VAT but lower subcutaneous AT (SCAT). IMAT seems to be involved in the pathogenesis of insulin resistance, as shown by the significant negative correlation with GIR. J. Magn. Reson. Imaging 2009. © 2009 Wiley‐Liss, Inc.
Change in serum COMP concentration due to ambulatory load is not related to knee OA Status
Authors: Mündermann Annegret , King Karen B. , Smith R. Lane , Andriacchi Thomas P. 
Published: May 2009

AbstractThe aim of this study was to test the hypothesis that a change in serum cartilage oligomeric matrix protein (COMP) concentration is related to joint load during a 30‐min walking exercise in patients with medial compartment knee osteoarthritis (OA) and in age‐matched control subjects. Blood samples were drawn from 42 patients with medial compartment knee OA and from 41 healthy age‐matched control subjects immediately before, immediately after, and 0.5, 1.5, 3.5, and 5.5 h after a 30‐min walking exercise on a level outdoor walking track at self‐selected normal speed. Serum COMP concentrations were determined using a commercial ELISA. Basic time–distance gait variables were recorded using an activity monitor. Joint loads were measured using gait analysis. Serum COMP concentrations increased immediately after the walking exercise (+6.3% and +5.6%; p < 0.001) and decreased over 5.5 h after the exercise (−11.1% and −14.6%; p < 0.040 and p = 0.001) in patients and control subjects, respectively. The magnitude of increase in COMP concentration did not differ between groups (p = 0.902) and did not correlate with any variables describing ambulatory loads at the joints of the lower extremity. These results, taken together with a previous study of a younger healthy population, suggest the possibility that the influence of ambulatory loads on cartilage turnover is dependent on age. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1408–1413, 2009
Diagnostic accuracy of neutrophil‐derived circulating free DNA (cf‐DNA/NETs) for septic arthritis
Authors: Lögters Tim , Paunel‐Görgülü Adnana , Zilkens Christoph , Altrichter Jens , Scholz Martin , Thelen Simon , Krauspe Rüdiger , Margraf Stefan , Jeri Teresa , Windolf Joachim , Jäger Marcus 
Published: May 2009

AbstractThe release of “neutrophil extracellular traps” (NETs) has been identified as a novel immune response in innate immunity. NETs are composed of neutrophil‐derived circulating free DNA (cf‐DNA) and neutrophil cytoplasm‐derived proteins such as proteases. In this study, we analyzed the putative diagnostic value of synovial cf‐DNA/NETs for identification of septic arthritis. Forty‐two patients with a joint effusion who had undergone arthrocentesis were included. From synovial fluid, cf‐DNA/NETs (j‐cf‐DNA) levels were directly quantified. Diagnostic value of j‐cf‐DNA was compared with white blood cells (WBC), synovial white blood cells (j‐WBC), C‐reactive protein (CRP), j‐IL‐6, j‐TNF alpha, j‐IL‐1 beta, and myeloperoxidase (j‐MPO). Sensitivity, specificity, positive and negative predictive value, as well as ROC‐curves for each parameter were calculated. Synovial fluid cf‐DNA/NETs values from patients with septic arthritis (3,286 ± 386 ng/ml, n = 9) were significantly increased compared to patients with noninfectious joint inflammation (1,040 ± 208 ng/ml, n = 17) or osteoarthritis (278 ± 34 ng/ml, n = 16, p < 0.01). In conjunction with j‐cf‐DNA, j‐IL‐6 and j‐IL‐1 beta were significantly elevated (p < 0.01), but WBC, CRP, and j‐WBC were not. At a cut‐off of 300 ng/ml, j‐cf‐DNA had a sensitivity of 0.89, a specificity of 1.0, a positive predictive value of 1.0, and a negative predictive value of 0.97. Receiver operation curves revealed largest areas under the curve for cf‐DNA/NETs (0.933) and j‐IL‐6 (0.951). cf‐DNA/NETs seem to be a valuable additional marker for the diagnosis of septic arthritis or periprosthetic infections. However, this result should be confirmed in a large clinical trial. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1401–1407, 2009
Near‐IR surface‐enhanced Raman spectrum of lignin
Authors: Agarwal Umesh P. , Reiner Richard S. 
Published: May 2009

AbstractCompacted powders of commercially available nano‐ and microparticles of silver were used to successfully induce the surface‐enhanced Raman scattering (SERS) effect in spruce milled‐wood lignin (MWL). For the two silver particle sizes used in this investigation, the spectra were mostly similar. Some general characteristics of the lignin SERS spectrum are described. The SERS technique was found to be sensitive for detecting lignin. Significant spectral changes were present between the SERS and normal Raman spectra of MWL. The SERS spectrum was assigned on the basis of literature‐reported vibrational assignments of lignin and its models. Based on significant changes in Raman features, we propose that the lignin is strongly adsorbed on silver. To determine whether SERS of lignin can be obtained directly from wood without its isolation, Wiley‐milled spruce wood (WMW) adsorbed on silver was studied. The results indicated that not only the surface‐enhancement effect was successfully induced in the WMW, but that its spectrum was similar to MWL SERS. Moreover, for WMW, no signals from the carbohydrate components were observed, and therefore, lignin was detected selectively. This nano‐ and microparticle‐based molecularly specific method is expected to make a significant contribution in identifying and investigating lignin in various lignin‐containing materials. Published in 2009 by John Wiley & Sons, Ltd.
Surgical techniques for the treatment of nasal valve collapse
Authors: Spielmann Patrick M. , White Paul S. , Hussain S. S. M. 
Published: May 2009

AbstractObjectives/Hypothesis:To critically evaluate the surgical treatment strategies for nasal valve collapse.Methods:A systematic review of studies to treat nasal valve collapse, using surgical methods, from 1970 to 2008. A search of EBM reviews, MEDLINE, and EMBASE was performed using the following search terms: “nasal valve collapse” AND “alar collapse,” “nasal valve insufficiency,” “alar insufficiency,” and “functional rhinoplasty.” The following outcome measures were sought: subjective symptom relief, cosmetic outcome, and objective measurements of nasal airway patency. The following were inclusion criteria: at least 10 patients in each study, stated aim to improve airway obstruction, and a minimum of 1 month follow‐up for every patient.Results:Our search identified 98 papers, which were then retrieved and analyzed. Of these, 43 met the inclusion criteria. No randomized controlled trials exist; one trial presented level IIIb evidence, but all other studies were classed as level IV. Seven authors present objective measurements of nasal airflow or cross‐sectional area, and four authors present validated outcome measures.Conclusions:A variety of focussed surgical techniques are described to deal with nasal valve collapse. We could find no randomized controlled trials on nasal valve surgery. Research in nasal valve surgery is frequently driven by technical description of surgical technique rather than the establishment of evidence of long‐term patient benefit. Although our understanding of the role of the nasal valve in the pathophysiology of nasal obstruction has improved vastly, the myriad of surgical techniques described perhaps reflects our uncertainty in choice of technique and in degree of patient benefit. Laryngoscope, 2009