bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influence of protective groups on diastereofacial selectivity of Diels‐Alder cycloaddition reactions
Authors: Gung Benjamin W. , Mareska David A. , Karipidis Anastas , Henry Thomas 
Published: January 2005

AbstractThe diastereofacial selectivity of both inter‐ and intramolecular Diels‐Alder reactions with dienes having an allylic stereogenic center has been studied by varying the allylic oxygen protective group. Four different hydroxy protective groups were investigated including benzyl, t‐butyldiphenylsilyl, triethylsilyl, and t‐butyldimethylsilyl ethers. For intermolecular reactions, the benzyl ether derivative gave the highest sπ‐facial selectivity through a transition state in which the allylic stereocenter favors the CH eclipsed conformation. For intramolecular cycloadditions, the t‐butyldimethylsilyl group gave a slightly higher selectivity than the benzyl ether derivative through a transition state in which the allylic stereocenter favors the CO eclipsed conformation. The opposite diastereofacial selectivity observed for inter‐ and intramolecular reactions is explained by considering both steric and electronic effects. © 1995 Wiley‐Liss, Inc.
A new approach in exciton‐coupled circular dichroism (ECCD)—insertion of an auxiliary stereogenic center
Authors: Person Richard V. , Monde Kenji , Humpf Hans‐ulrich , Berova Nina , Nakanishi Koji 
Published: January 2005

AbstractThere are cases in which exciton coupling between two chromophores does not occur because the two electric transition moments which should interact are coplanar. This is seen with cyclohexane‐1,4‐diols (both ee or ea) and a wide variety of 3‐hydroxy carotenoids, 3‐hydroxyretinoids, etc. A general approach to deal with such cases is to acylate one of the hydroxyl groups with a chiral allenic acid substituted with a suitable chromophore, e.g., CHROMCHCCH‐COOH. The allenic bond introduces a 90° twist at the italicized central carbon so that the allenic CHROM now couples with the second chromophore. This concept of introducing an auxiliary allenic center should be of general applicability in other similar cases. © 1995 Wiley‐Liss, Inc.
Stereoselective binding of isradipine to human plasma proteins
Authors: Oravcová Jana , Sojková Dagmar , Bencsíková Erika , Bohov Pavol , Trnovec Tomáš 
Published: January 2005

AbstractIsradipine (PN 200–110) is a highly potent calcium entry blocker with an asymmetrically substituted dihydropyridine ring (methyl‐ and isopropylester, respectively). The binding of the (+)‐(S)‐isradipine and (−)‐(R)‐isradipine to isolated human serum albumin (HSA, 30 μmol/l) and α1‐acid glycoprotein (AAG, 10 μmol/l) has been studied in vitro over a wide range of isradipine concentrations (0.06–20 μmol/l) using high‐performance liquid chromatography (HPLC). HPLC experiments revealed that both isradipine enantiomers were bound to one class of high‐affinity binding sites on the AAG molecule (n(S) = 0.83 ± 0.05, Ka(S) = (1.33 ± 0.25) × 106 1/mol, n(R) = 0.85 ± 0.07, Ka(R) = (1.17 ± 0.44) × 107 l/mol). The (R)‐enantiomer also exhibited an interaction with the secondary low‐affinity binding sites (n′K′a (R) = (2.66 ± 0.65) × 104 l/mol). In contrast, the pharmacologically more potent (+)‐(S)‐enantiomer was more strongly bound to HSA than its optical antipode (n(S) = 1.07 ± 0.07, Ka(S) = (1.76 ± 0.26) × 105 l/mol, nKa(R) = (3.62 ± 0.06) × 104 l/mol). In general, the resulting binding characteristics of individual isradipine enantiomers showed stereoselectivity, but this was opposite for the two most important plasma binding proteins. The process of accumulation of isradipine by human platelets in the therapeutically relevant range (10–80 ng/ml) at 37°C was devoid of stereoselectivity. © 1995 Wiley‐Liss, Inc.
Chiroptical methods in conformational analysis
Authors: Sandström Jan 
Published: January 2005

AbstractCD spectra of flexible organic molecules in solution are normally very sensitive to conformation. In a system composed of two or more chromophores joined by one or more single bonds and with one fixed or strongly preferred conformation, it is often possible to reproduce the CD spectrum by semiempirical calculations based on interactions between the electronic transitions in the respective chromophores. In a system containing two or more conformations of appreciable weight, the observed CD spectrum is the superposition of those of the individual conformations and has to be analyzed in terms of the individual calculated spectra and the relative energies of the respective conformations. The effect of temperature variation on conformational equilibria and on the composite CD spectra will be discussed and exemplified. © 1995 Wiley‐Liss, Inc.
Chirality induction in cyclocopolymerization of bis(p‐vinylbenzoate)s of carbohydrates with styrene: Chiroptical study of resulting polymer by exciton chirality method
Authors: Haba Osamu , Yokota Kazuaki , Kakuchi Toyoji 
Published: January 2005

AbstractThree bis(p‐vinylbenzoate) monomers, 2,3‐O‐isopropylidene‐1,4‐bis‐O‐(p‐vinylbenzoyl)‐L‐threitol (BIT), methyl 4,6‐O‐isopropylidene‐2,3‐bis‐O‐(p‐vinylbenzoyl)‐α,D‐glucopyranoside (BIG), and 1,2:5,6‐di‐O‐isopropylidene‐3,4‐bis‐O(p‐vinylbenzoyl)‐D‐mannitol (BIM), were prepared and cyclocopolymerized with styrene. The resulting copolymers were hydrolyzed with KOH to remove the chiral template, and treated with diazomethane to give poly[(methyl p‐vinylbenzoate)‐co‐styrene] [poly(MVB‐co‐St)]. All the poly(MVB‐co‐St) had a specific rotation and their CD spectra exhibit a split Cotton effect. Poly(MVB‐co‐St) derived from poly(BIT‐co‐St) showed a positive Cotton effect at 255 nm and a negative one at 235 nm. According to the exciton chirality method, poly(MVB‐co‐St) possessed negative chirality, and the stereochemistry of the carbon atom attached to the 4‐benzoyl group had the S configuration. The absolute configuration of poly(MVB‐co‐St) was determined as R for the BIG/St system and S for the BIM/St system. © 1995 Wiley‐Liss, Inc.
Degradation and racemization of zopiclone enantiomers in plasma and partially aqueous solutions
Authors: Fernandez Christina , Gimenez François , Mayrargue Joelle , Thuillier Alain , Farinotti Robert 
Published: January 2005

AbstractWe investigated the degradation and racemization of zopiclone (ZOP) enantiomers in plasma and partially aqueous solutions (ethanol:phosphate buffer). Degradation and racemization increased with increasing pH and temperature. Degradation products were identified by means of mass spectrometry, which revealed hydrolysis of the carbamate function and opening of the pyrrolidone ring. In plasma, neither degradation nor racemization occurred after 6 months of storage at ‐20°C and subsequent extraction. © 1995 Wiley‐Liss, Inc.
Substitution and racemization of 3‐hydroxy‐ and 3‐alkoxy‐1,4‐benzodiazepines in acidic aqueous solutions
Authors: Yang Shen K. 
Published: January 2005

AbstractOxazepam (OX), 3‐O‐methyloxazepam, 3‐O‐ethyloxazepam, temazepam (TMZ), 3‐O‐methyltemazepam, and 3‐O‐ethyltemazepam underwent acid‐catalyzed nucleophilic substitution reaction (hydrolysis) in an acetonitrile–oxygen‐18 water mixture to form either OX or TMZ in which the 3‐hydroxyl group was either partially or fully labeled with an oxygen‐18 atom. The dependence of the hydrolysis rates on solvent composition, temperature, ionic strength, and in deuterated solvent was studied by reversed‐phase high‐performance liquid chromatography (HPLC). The rates of racemization of enantiomeric compounds in acidic aqueous solutions were studied by both spectropolarimetry and chiral stationary phase HPLC. In acetonitrile: 2.5 M H2SO4 (4:1, v/v) at 50°C, enantiomers of OX and TMZ underwent racemization at rates ≥40‐fold faster than the rates of hydrolysis. Enantiomeric 3‐O‐alkyl derivatives of OX and TMZ in acidic aqueous solutions did not themselves undergo racemization and it was their hydrolysis products (either OX or TMZ) that underwent racemization. © 1995 Wiley‐Liss, Inc.
Inversion of (R)‐ to (S)‐ketoprofen in eight animal species
Authors: Aberg Gunnar , Ciofalo Vincent B. , Pendleton Robert G. , Ray Gene , Weddle Diann 
Published: January 2005

AbstractThe (R)‐enantiomer of the NSAID ketoprofen was administered orally at 20 mg/kg to a series of 8 animal species. In all species, a highly significant degree of inversion occurred after 1 h which varied from 27% (gerbil) to 73% (dog) and persisted or increased in plasma samples obtained 3 h after drug administration. Although the (R)‐enantiomer was inactive as an inhibitor of cyclooxygenase, the analgesic effects of that isomer was almost the same as the (S)‐isomer in animal analgesic assays, following oral administration of the drugs to mice and rats. Taken together, the present results suggest that (R)‐ketoprofen administered alone functioned primarily as a prodrug for (S)‐ketoprofen under the experimental conditions of this study. © 1995 Wiley‐Liss, Inc.
Mechanisms of enantiomeric resolution in cyclodextrin‐modified capillary electrophoretic separations of binaphthyl compounds
Authors: Copper Christine L. , Davis Joe B. , Sepaniak Michael J. 
Published: January 2005

AbstractThe enantiomers of 1,1′‐bi‐2‐naphthol, 1,1′‐binaphthyl diyl hydrogen phosphate, and 1,1′‐binaphthyldicarboxylic acid are separated using capillary electrophoresis with cyclodextrins added to the running buffer. It is demonstrated that the type and concentration of cyclodextrin employed are critical for maximum enantiomeric resolution. A modified version of a previously described model of enantiomeric separations in capillary electrophoresis is shown to support the observed separation behavior. Molecular modeling is employed to calculate interaction energies between the various enantiomers and cyclodextrins. A reasonable correlation between these computationally derived interaction energies and separation behavior resulted from a statistical mechanical treatment of the molecular modeling data. The importance of hydrogen bonding in inclusion complex formation was probed and the effects of minimization and solvation in molecular modeling calculations are also discussed. © 1995 Wiley‐Liss, Inc.
Rapid chiral separation methods development by cyclodextrin‐mediated capillary electrophoresis for acidic and basic compounds
Authors: Guttman András , Brunet Sandra , Jurado Caroline , Cooke Nelson 
Published: January 2005

AbstractChiral separation methods development using conventional techniques such as GC or HPLC requires a lot of experience, effort, and expense, due to the wide diversity of the optically active solutes and their possible chiral selectors. Capillary electrophoresis has received increased attention as an alternative technique for chiral separation due to its inherent high efficiencies and ease of methods development. However, due to the wide variety of chiral selectors available in CE, the benefits of this technique might be diminished without an appropriate methods development scheme. In this paper detailed examples are shown for fast, efficient, and predictable chiral capillary electrophoresis separation methods development based on a new and systematic theory. Optimized separations and their parameters are presented for several enantiomeric acids and bases. All the three possible cases, such as the use of low and high pH, as well as pH = pK buffer systems are thoroughly discussed. © 1995 Wiley‐Liss, Inc.
Low configurational stability of amfepramone and cathinone: Mechanism and kinetics of chiral inversion
Authors: Reist Marianne , Christiansen Lisbeth Hein , Christoffersen Pia , Carrupt Pierre‐Alain , Testa Bernard 
Published: January 2005

AbstractThe low configurational stability of two model compounds, the anorectic drug amfepramone and one of its basic metabolites, rac‐cathinone, was examined for its mechanism and kinetics. Assuming a common intermediate for chiral inversion and deuteration, the rates of racemization were determined by the indirect method of proton–deuterium substitution monitored by 1H‐NMR. The rate of racemization increased linearily with increasing pD. At a pD of 7.4, the rate of racemization of both aminoketones was markedly dependent on buffer concentration, indicating a mechanism of general‐base catalysis. The reactions were some five to six times faster in phosphate buffers than in hydroxylamine buffers of identical molarity. Amfepramone racemized about five times faster than the primary amine cathinone. One implication of these findings is that amfepramone and cathinone may be subject in vivo to chiral inversion catalyzed by numerous endogenous bases. As a result, it will be misleading to extrapolate rates of inversion expected in plasma from those measured in buffer solutions. © 1995 Wiley‐Liss, Inc.
Chromatographic resolution of some cyclic sulfoximides derived from prochiral and chiral sulfoxides
Authors: Allenmark Stig , Andersson Christina , Widell Petra 
Published: January 2005

AbstractThree endocyclic sulfoximides of the 1‐aryl‐ and 1‐alkyl‐3‐oxo‐benzo[d]‐isothia (IV)‐azole 1‐oxide type (1‐substituent = 2′‐carboxyphenyl, 2′‐carbethoxyphenyl, and octyl, respectively) were found to be well resolved on a chiral phase derived from bovine serum albumin (BSA). Selectivities (α) of 1.74, 1.12, and 1.44, respectively, were obtained. The retention behaviour of 1‐octyl‐3‐oxo‐benzo[d]isothia(IV)‐azole 1‐oxide was further investigated in some detail as a function of the mobile phase composition and the elution order was established from optically active material obtained from the enantiopure sulfoxide precursor. An enantiomeric excess of 85.4% was obtained in the cyclocondensation reaction of the octyl‐substituted sulfoxide precursor with hydrazoic acid to the corresponding endocyclic sulfoximide. © 1995 Wiley‐Liss, Inc.
Folding of aminosuccinyl peptides: Thermodynamic data from temperature dependent circular dichroism measurements
Authors: Capasso Sante , Mazzarella Lelio , Zagari Adriana 
Published: January 2005

AbstractThe conformational equilibrium of aminosuccinyl peptides between extended conformations and an intramolecularly hydrogen bonded type II′ β‐turn conformation has been studied on the peptide Boc‐L‐Asu‐Gly‐L‐Ala‐OMe (Asu = aminosuccinyl residue) by means of temperature dependence of circular dichroism spectra.Owing to the peculiar chiroptical and conformational properties of the Asu residue, this technique proved to be very useful for deriving thermodynamic data for the above folding process. The value of ΔH0 (−6.6 kJ mol−1), obtained for the peptide studied in a chloroformacetonitrile mixture, shows that the lower energy of the folded conformer is primarily due to the characteristic intramolecular hydrogen bond of the β turns. © 1995 Wiley‐Liss, Inc.
Stereoselective pharmacokinetics of oxprenolol, propranolol, and verapamil: Species differences and influence of endotoxin
Authors: Laethem Martine E. , Belpaire Frans M. , Wijnant Pascal , Bogaert Marc G. 
Published: January 2005

AbstractThe influence of endotoxin‐induced inflammation was studied on the pharmacokinetics of the enantiomers of the racemic drugs oxprenolol, propranolol, and verapamil in rabbits and dogs. Enantioselective pharmacokinetics were seen for oxprenolol and propranolol in the rabbit and for propranolol and verapamil in the dog. In the dog, the enantioselective differences in plasma concentrations are due to differences in both protein binding and metabolism, whereas in the rabbit the differences are due solely to differences in metabolism. In both species endotoxin treatment increases the plasma concentrations of the enantiomers of the three drugs; both protein binding and metabolism are influenced. In rabbits and in dogs, the influence of endotoxin on the disposition of the three drugs is less enantioselective than was previously observed in the rat. © 1995 Wiley‐Liss, Inc.
Discrimination in resolving systems II: Ephedrine‐substituted mandelic acids
Authors: Valente Edward J. , Miller Christopher W. , Zubkowski Jeffrey , Eggleston Drake S. , Shui Xiuiqi 
Published: January 2005

AbstractBinary diastereomeric (‐) (1R,2S)‐ephedrine salts of various mandelic acids obtained from 95% ethanol show considerable differences in solubility. Structures and some properties of the less‐soluble (L) and more‐soluble (M) solid phases of (‐)‐ephedrine with unsubstituted mandelic acid, 2‐, 3‐, and 4‐monosubstituted halo (F, Cl, Br) mandelic acids, and 3‐ and 4‐methylmandelic acids have been determined. Salts were found to be binary, without solvent of crystallization, and composed of double‐layered arrays of alternating anions and cations linked by H‐bonds normal to the layers. H‐bonding links charged donors and acceptors usually along a crystallographic 2‐fold screw axis. A striking discrimination is evident in that the (2R)‐mandelate salts typically display a compact four‐atom chain as the H‐bonding repeating unit [+N—H…O(—C−—O)…H‐N′, C21(4)] while the (2S)‐mandelate salts adopt a more dimensionally variable six‐atom chain repeating unit [+N—H…O—C−—O…H—N′, C22(6)]. Two distinct packing schemes display the shorter H‐bonding chain of the (2R)‐mandelates which always occurs with ephedrinium ions in the fully extended conformation. Slightly greater packing efficiency and H‐bonding energies of the (2R)‐mandelate salts correlates with increased fusion points, lower solubilities (95% ethanol), and higher heats of fusion relative to the phase adopted by their diastereoisomers. In contrast, (2S)‐mandelate salts exhibit considerably more structural variability involving all three major ephedrinium conformations, and at least four distinct packing motifs. Mandelates with larger 3′‐substituents (Cl, Br, methyl) show similar property discriminations, but these occur with an opposing trend, that is, between phases in which the less‐soluble salts contain (2S)‐mandelates. Salts with 2‐bromomandelate do not show property disparities and their structures are dissimilar to the other phases. © 1995 Wiley‐Liss, Inc.
The impact of CAG repeats in exon 1 of the androgen receptor on disease progression after prostatectomy
Authors: Powell Isaac J. , Land Susan J. , Dey Jyotirmoy , Heilbrun Lance K. , Hughes Mark R. , Sakr Wael , Everson Richard B. 
Published: January 2005

AbstractBACKGROUNDThe authors examined the impact of the number of CAG repeats in exon 1 of the androgen receptor on disease progression among men with prostate carcinoma after prostatectomy. This polymorphism has been associated with alterations in activity of the androgen receptor in in vitro systems and with the risk of clinically diagnosed prostate carcinoma in some epidemiologic studies. An earlier series found that, among men at low risk of progressive disease, a small number of CAG repeats predicted a high risk of recurrence, and the impact of CAG repeats varied among men with different risks of progressive disease.METHODSThe authors analyzed specimens from a large clinical series of fixed tissue specimens from men who underwent prostatectomy at a single institution, including 413 American white men (WM) and 298 African‐American men (AAM), with 5–10 years of available clinical follow‐up.RESULTSThere was little association between the number of CAG repeats and extent of disease, Gleason score, and preoperative PSA level at diagnosis. Overall, patients who had > 18 CAG repeats had a greater risk of recurrence compared with patients who had ≤ 18 CAG repeats (hazard ratio [HR] = 1.52;P= 0.03). Excess risk was not found among men who were at low risk of recurrence (HR = 0.93;P= 0.96); however, among men who were at high risk of recurrence, the risk elevated for WM (HR = 1.75;P= 0.28), AAM (HR = 1.49;P= 0.06), and both races combined (HR = 1.53;P= 0.03).CONCLUSIONSOverall, men with prostate carcinoma who had > 18 CAG repeats had an estimated 52% increased risk of disease recurrence. The increased risk could be attributed to men who were at high risk of recurrence. Cancer 2005. © 2005 American Cancer Society.
Protein expression and gene amplification of epidermal growth factor receptor in thymomas
Authors: Ionescu Diana N. , Sasatomi Elizaburo , Cieply Kathleen , Nola Marin , Dacic Sanja 
Published: January 2005

AbstractBACKGROUNDEpidermal growth factor receptor (EGFR) overexpression and amplification are important prognostic factors in many solid tumors and anti‐EGFR antibody‐based therapy is now available as a promising therapeutic modality. There is little information in the literature regarding the biologic role of EGFR in thymomas that are characterized by variable clinical presentations, histologic heterogeneity, and unpredictable behavior.METHODSProtein expression and gene amplification of EGFR were investigated in 32 thymomas (9 World Health Organization [WHO] type A, 5 type AB, 7 type B2, 7 type B3, 4 type C) using immunohistochemistry and fluorescence in situ hybridization (FISH). FISH analysis included assessment of the average number of copies of the EGFR gene per cell, the average ratio of the EGFR gene to chromosome 7 copy numbers, and ploidy.RESULTSThe results of FISH analysis showed statistically significant correlation with WHO histologic type, invasion, advanced clinical stage, but not with tumor size and outcome. Thymomas associated with myasthenia gravis more frequently showed hyperploidy when compared with sporadic tumors, but there was no difference in EGFR gene amplification. EGFR protein expression assessed by immunohistochemistry did not correlate with any studied clinicopathologic variables. There was poor correlation between the protein expression and gene amplification, only 7 of 23 specimens (30%).CONCLUSIONSThe potential role of EGFR in the pathogenesis of advanced‐stage thymomas indicated that evolving anti‐EGFR antibody therapy may be considered as a treatment option. Cancer 2005. © 2005 American Cancer Society.
A multicenter, randomized, Phase II study of cisplatin, etoposide, and gemcitabine or cisplatin plus gemcitabine as first‐line treatment in patients with poor‐prognosis small cell lung carcinoma
Authors: De Marinis Filippo , Nelli Fabrizio , Lombardo Marco , Ferraú Francesco , Barbera Santi , Bertetto Oscar , Barni Sandro , Michetti Giovanni , Labianca Roberto , Gridelli Cesare 
Published: January 2005

AbstractBACKGROUNDThe objective of this study was to evaluate the activity and toxicity of combined cisplatin, etoposide, and gemcitabine (PEG) and combined cisplatin plus gemcitabine (PG) in previously untreated patients with extensive‐stage and poor‐prognosis limited‐stage small‐cell lung carcinoma.METHODSOne hundred forty patients (70 patients in two arms) were randomized to receive either cisplatin 70 mg/m2 on Day 1, etoposide 50 mg/m2 on Days 1–3, and gemcitabine 1000 mg/m2 on Days 1 and 8 or cisplatin 70 mg/m2 on Day 1 plus gemcitabine 1250 mg/m2 on Days 1 and 8. Both regimens were recycled every 21 days.RESULTSIn total, 626 cycles were delivered (303 cycles of PEG and 323 cycles of PG), with a median of 4 cycles per patient in both arms. The objective response rate was 63% (95% confidence interval [95%CI], 49–71%) for PEG and 57% (95%CI, 43–67%) for PG, with the suggestion of a higher complete response rate in the PEG arm (18.6% and 4.3%, respectively). A similar time to disease progression (6 months in the PEG arm and 7 months in the PG arm) and a similar median survival (9.5 months in the PEG arm and 10 months in the PG arm) were observed in both arms. The PEG regimen was associated with more severe hematologic toxicity in terms of neutropenia, febrile neutropenia, and a higher rate of treatment delays and dose reductions, whereas nonhematologic toxicities did not differ between the two arms.CONCLUSIONSAccording to the results of this Phase II randomized trial, the PEG regimen produced a higher complete response rate but more toxicity compared with the PG regimen in patients with extensive‐stage or poor‐prognosis, limited‐stage small cell lung carcinoma. Cancer 2005. © 2005 American Cancer Society.