bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glial‐mediated neuroprotection: Evidence for the protective role of the NO‐cGMP pathway via neuron–glial communication in the peripheral nervous system
Authors: Thippeswamy Thimmasettappa , Mckay Jennifer S. , Morris Richard , Quinn John , Wong Liang‐Fong , Murphy David 
Published: September 2004

AbstractThe NO‐cGMP pathway has emerged as a neuroprotective signaling system involved in communication between neurons and glia. We have previously shown that axotomy or nerve growth factor (NGF)‐deprivation of dorsal root ganglion (DRG) neurons leads to increased production of NO and at the same time an increase in cGMP production in their satellite glia cells. Blockade of NO or its receptor, the cGMP synthesizing enzyme soluble guanylate cyclase (sGC), results in apoptosis of neurons and glia. We now show that co‐culture of neonatal DRG neurons with either Schwann cells pre‐treated with an NO donor or a membrane‐permeant cGMP analogue; or neurons maintained in the medium from Schwann cell cultures treated in the same way, prevents neuronal apoptosis. Both NO donor and cGMP treatment of Schwann cells results in synthesis of NGF and NT3. Furthermore, if the Schwann cells are previously infected with adenoviral vectors expressing a dominant negative sGC mutant transgene, treatment of these Schwann cells with an NO donor now fails to prevent neuronal apoptosis. Schwann cells treated in this way also fail to express neither cGMP nor neurotrophins. These findings suggest NO‐sGC‐cGMP‐mediated NGF and NT3 synthesis by Schwann cells protect neurons. © 2004 Wiley‐Liss, Inc.
Amino acid transporter SNAT5 localizes to glial cells in the rat brain
Authors: Cubelos Beatriz , González‐González Inmaculada M. , Giménez Cecilio , Zafra Francisco 
Published: September 2004

AbstractThe SNAT5 transporter is a neutral amino acid carrier whose function remains unclear. Structural and mechanistically, SNAT5 is closely related to the SNAT3 transporter that mediates the efflux of glutamine from glial cells and that participates in the glutamate‐glutamine cycle in the brain. In this study, we have analyzed the distribution of SNAT5 in the rat central nervous system using specific antibodies. Through immunoblotting we observed that SNAT5 is ubiquitously but unevenly distributed in the CNS. It accumulates most intensely in the neocortex, the hippocampus, the striatum, and the spinal cord, whereas moderate levels were found in the thalamus, hypothalamus, and brainstem. Light microscopy revealed that the distribution of SNAT5 paralleled that of the vesicular glutamate transporter vGLUT1 in the forebrain regions, whereas in the diencephalon and brainstem, SNAT5 staining was better correlated with that of vGLUT1 and vGLUT2. However, the cellular localization differed from that of the glutamatergic markers, since SNAT5 was expressed exclusively in astrocyte cell bodies and their processes, ensheathing glutamatergic GABAergic and glycinergic terminals. The presence of SNAT5 in astrocyte processes was confirmed by electron microscopy. They were seen not only to surround different neuronal structures, but they were also found in astrocyte endfeet. Taking into consideration the higher levels of SNAT5 in the neighborhood of glutamatergic terminals and the ability of this transporter family to promote the efflux of amino acids from intracellular stores (including glutamine and perhaps glycine), this transporter is likely to be involved in glutamatergic pathways in the brain. © 2004 Wiley‐Liss, Inc.
Role of Na+‐H+ and Na+‐Ca2+ exchange in hypoxia‐related acute astrocyte death
Authors: Bondarenko Alexander , Svichar Nataliya , Chesler Mitchell 
Published: September 2004

AbstractCultured astrocytes do not succumb to hypoxia/zero glucose for up to 24 h, yet astrocyte death following injury can occur within 1 h. It was previously demonstrated that astrocyte loss can occur quickly when the gaseous and interstitial ionic changes of transient brain ischemia are simulated: After a 20–40‐min exposure to hypoxic, acidic, ion‐shifted Ringer (HAIR), most cells died within 30 min after return to normal saline (i.e., “reperfusion”). Astrocyte death required external Ca2+ and was blocked by KB‐R7943, an inhibitor of reversed Na+‐Ca2+ exchange, suggesting that injury was triggered by a rise in [Ca2+]i. In the present study, we confirmed the elevation of [Ca2+]i during reperfusion and studied the role of Na+‐Ca2+ and Na+‐H+ exchange in this process. Upon reperfusion, elevation of [Ca2+]i was detectable by Fura‐2 and was blocked by KB‐R7943. The low‐affinity Ca2+ indicator Fura‐FF indicated a mean [Ca2+]i rise to 4.8 ± 0.4 μM. Loading astrocytes with Fura‐2 provided significant protection from injury, presumably due to the high affinity of the dye for Ca2+. Injury was prevented by the Na+‐H+ exchange inhibitors ethyl isopropyl amiloride or HOE‐694, and the rise of [Ca2+]i at the onset of reperfusion was blocked by HOE‐694. Acidic reperfusion media was also protective. These data are consistent with Na+ loading via Na+‐H+ exchange, fostering reversal of Na+‐Ca2+ exchange and cytotoxic elevation of [Ca2+]i. The results indicate that mechanisms involved in pH regulation may play a role in the fate of astrocytes following acute CNS injuries. © 2004 Wiley‐Liss, Inc.
Prioritizing new over old: An fMRI study of the preview search task
Authors: Olivers Christian N.L. , Smith Stephen , Matthews Paul , Humphreys Glyn W. 
Published: September 2004

AbstractIn visual search, observers can successfully ignore temporally separated distractors that are presented as a preview before onset of the search display. Previous behavioral studies have demonstrated the involvement of top–down selection mechanisms in preview search, biasing attention against the old set in favor of the more relevant new set. Using functional magnetic resonance imaging, we replicate and extend findings showing the involvement of superior and inferior parietal areas in the preview task when compared to both a relatively easy single‐set search task and a more effortful full‐set search task. In contrast, the effortful full‐set search showed activation in the dorsolateral prefrontal cortex when compared to the single‐set search, suggesting that this area is involved in rejecting additional distractors that could not be separated in time. Hum. Brain Mapp 24:69–78, 2005. © 2004 Wiley‐Liss, Inc.
Synthesis of {242}‐ and {323}‐p‐Octiphenyls
Authors: Baudry Yoann , Ronan Dawn , Jeannerat Damien , Matile Stefan 
Published: September 2004

AbstractThe introduction of rigid‐rod molecules as privileged scaffolds has opened routes to otherwise problematic supramolecular architecture like artificial β‐barrels and functional supramolecules covering pores, hosts, sensors, and catalysts. The usefulness of p‐oligophenyls for the construction of functional barrel‐stave architecture has, however, been limited by uniform substitution along the rigid‐rod scaffold. The objective of this report is to overcome this obstacle for the synthesis of p‐octiphenyls with orthogonally protected carboxylic acid groups along the rigid‐rod scaffold. In the reported {242}‐p‐octiphenyl 1, the two peripheral arene moieties carry carboxylic acid groups protected as benzyl esters, whereas the four central carboxylic acid groups are protected orthogonally as tert‐butyl esters (Scheme 2). The complementary orthogonal protection of the three peripheral and the two central arenes is achieved in the {323}‐p‐octiphenyl 2 (Scheme 3). The realized {242}‐ and {323}‐p‐octiphenyls 1 and 2, respectively, provide a complete set for the general access to refined rigid‐rod barrel‐stave architecture with maximized functional plasticity. The need for resolution‐enhanced (aliased) HMBC 2D‐NMR spectroscopy to characterize these refined oligomers is described in the following publication in this issue of Helv. Chim. Acta.
NMR Characterization of Complex p‐Oligophenyl Scaffolds by Means of Aliasing Techniques to Obtain Resolution‐Enhanced Two‐Dimensional Spectra
Authors: Jeannerat Damien , Ronan Dawn , Baudry Yoann , Pinto André , Saulnier Jean‐Paul , Matile Stefan 
Published: September 2004

AbstractThe usefulness of computer‐assisted aliasing to secure maximal resolution of signal clusters in 1H‐ and 13C‐NMR spectra (which is essential for structure determination by HMBC 2D NMR spectroscopy) in minimal acquisition time is exemplified by the complete characterization of the two complementary p‐octiphenyls 1 and 2 with complex substitution patterns. The need for digital resolution near 1 Hz/pt to dissect the extensive signal clusters in the NMR spectra of these refined oligomers excluded structure determination under routine conditions. High resolution was secured by exploiting the low signal density in the 13C dimension of HMBC spectra by using computer‐assisted aliasing to maximize signal density. Based on the observed shifts in DEPT and 1H‐decoupled 13C‐NMR spectra of 1 and 2, computer‐assisted aliasing allowed to reduce the number of required time increments by a factor of 20 to 30 compared to full‐width spectra with identical resolution. Without signal‐to‐noise constraints, this computer‐assisted aliasing reduced the acquisition time for high‐resolution NMR spectra needed for complete characterization of refined oligomers 1 and 2 by the same factor (e.g., from over a day to about an hour). With resolved signal clusters in fully aliased HSQC and HMBC spectra, unproblematic structure determination of 1 and 2 is demonstrated by unambiguous assignment of all C‐ and H‐atoms. These findings demonstrate that computer‐assisted aliasing of the underexploited 13C dimension makes extensive molecular complexity accessible by conventional multidimensional heteronuclear NMR experiments without extraordinary efforts.
Computational Interpretation of Vibrational Optical Activity: The ROA Spectra of (4S)‐4‐Methylisochromane and the (4S)‐Isomers of Galaxolide®
Authors: Zuber Gérard , Hug Werner 
Published: September 2004

AbstractThe reliable computation of Raman‐optical‐activity (ROA) spectra of molecules of the size of the title compounds has, until now, not been possible. We show that our rarefied basis sets yield results in good agreement with the experimental data for (4S)‐4‐methylisochromane (=(4S)‐3,4‐dihydro‐4‐methyl‐1H‐2‐benzopyran; 1), provided the equilibrium between the pseudo‐equatorial and the pseudo‐axial conformers is taken into account. Comparison between the measured and the computed ROA back‐scattering spectra allows the unequivocal assignment of the absolute configuration of the molecule. Comparison with more‐approximate calculations for the larger (4S)‐isomers of Galaxolide® (2), which contain the (4S)‐4‐methylisochromane moiety, shows large‐scale group frequencies on the same chiral fragments of the two molecules. The data confirm that ROA can be generated by interactions extending over several bonds, i.e., over larger distances than can be probed by NMR spectroscopy. Thus, the absolute configuration at C(7) of Galaxolide® is assignable independently of that at C(4). The computation of ROA for forward‐scattering, which will soon be measurable for Galaxolide®, suggests that this scattering geometry provides additional stereochemical information that will be valuable in situations where absolute configurations at several stereogenic centers have to be assigned.
7‐Iodo‐5‐aza‐7‐deazaguanine: Syntheses of Anomeric D‐ and L‐Configured 2‐Deoxyribonucleosides
Authors: Lin Wenqing , Zhang Xiaomei , Seela Frank 
Published: September 2004

AbstractIodination of N2‐isobutyryl‐5‐aza‐7‐deazaguanine (7) with N‐iodosuccinimide (NIS) gave 7‐iodo‐N2‐isobutyryl‐5‐aza‐7‐deazaguanine (8) in a regioselective reaction (Scheme 1). Nucleobase‐anion glycosylation of 8 with 2‐deoxy‐3,5‐di‐O‐toluoyl‐α‐D‐ or α‐L‐erythro‐pentofuranosyl chloride furnished anomeric mixtures of D‐ and L‐nucleosides. The anomeric D‐nucleosides were separated by crystallization to give the α‐D‐anomer and β‐D‐anomer with excellent optical purity. Deprotection gave the 7‐iodo‐5‐aza‐7‐deazaguanine 2′‐deoxyribonucleosides 3 (β‐D; ≥99% de) and 4 (α‐D; ≥99% de). The reaction sequence performed with the D‐series was also applied to L‐nucleosides to furnish compounds 5 (β‐L; ≥99% de) and 6 (α‐L; ≥95% de).
Stereospecific Synthesis of Carbanucleotides Designed for Antisense Methodology
Authors: Zhu Xue‐Feng , Nydegger Freddy , Gossauer Albert 
Published: September 2004

AbstractA short stereospecific synthesis of the carbocyclic 2′‐deoxynucleoside analogues 36 and 37 (Schemes 2 and 5) and 45 and 46 (Schemes 2 and 6) starting from optically active 8,9,10‐trinorborn‐5‐en‐2‐one (1) is described. As two functional groups capable to react with each other are present in the same molecule of the synthetic carbanucleosides, the latter can form polymers similar to oligonucleotides.
New C(4)‐Functionalized Colchicine Derivatives by a Versatile Multicomponent Electrophilic Aromatic Substitution
Authors: Bensel Nicolas , Lagnoux David , Niggli Verena , Wartmann Markus , Reymond Jean‐Louis 
Published: September 2004

AbstractElectrophilic alkylation of colchicine at C(4) was accomplished by a multicomponent aromatic electrophilic substitution reaction with electrophilic aldehydes and carboxylic acids or amides in H2SO4. A series of new derivatives were obtained and evaluated for their antiproliferative effect towards various tumor cell lines, and their stimulatory effect on the development of polarity in human neutrophils.
Oligonucleotide Analogues with a ‘Nucleobase‐Including Backbone’. Part 10
Authors: Matthews Andrew John , Bhardwaj Punit Kumar , Vasella Andrea 
Published: September 2004

AbstractThe dinucleoside analogues 24, 25, 28–30, and 33 associate in CDCl3 solution. Association constants, as determined from the concentration‐dependent chemical shift for HN(3) of the uridine moiety and from thermodynamic parameters, range from 265 M−1 (33) to 3220 M−1 (30). The association of 31 in CDCl3 is too strong to be determined (concentration independent δ(HN(3)) of ca. 12.8 ppm) and the fully deprotected dimer 32 proved insufficiently soluble in CDCl3. This observation strongly evidences that structural differentiation of oligonucleotides and their analogues into backbone and nucleobases is not required for pairing. The dinucleotide analogues were prepared by O‐alkylation of C(8)‐unsubstituted or of C(8)‐oxymethylated, partially protected adenosines by the C(6)‐mesyloxy‐ or C(6)‐halomethylated uridines 20–22, followed by partial or total deprotection.
Regio‐ and Stereoselective 1,3‐Oxathiolane Formation in the Reaction of Thiolactones with Optically Active Oxiranes
Authors: Fu Changchun , Linden Anthony , Heimgartner Heinz 
Published: September 2004

AbstractThe reactions of 3H‐isobenzofuran‐1‐thione (1) with (S)‐2‐methyloxirane (2) and (R)‐2‐phenyloxirane (6) in the presence of SiO2 in anhydrous CH2Cl2 led to two pairs of diastereoisomeric spirocyclic 1,3‐oxathiolanes, i.e., 3 and 4 with a Me group at C(5′), and 7 and 8 with a Ph group at C(4′), respectively (Schemes 2 and 3). In both cases, 3H‐isobenzofuran‐1‐one (5) was formed as a main product. The analogous reactions of 3,4‐dihydro‐2H‐[1]benzopyran‐2‐thione (9) and 3,4,5,6‐tetrahydro‐2H‐pyran‐2‐thione (14) with 2 and 6 yielded four pairs of the corresponding diastereoisomeric spirocyclic compounds 10 and 11, 12 and 13, 15 and 16, and 18 and 19, respectively (Schemes 4–7). In the reaction of 14 with 6, the 1,3‐oxathiolane 20 with a Ph group at C(2) was also formed. The structures of 3, 7, 8, 10, 19, and 20 were established by X‐ray crystallography (Figs. 1–4). In contrast to the thiolactones 1, 9, and 14, the thioesters 21a–21d did not react with (R)‐2‐phenyloxirane (6) either in the presence of SiO2 or under more‐drastic conditions with BF3⋅Et2O or SnCl4 (Scheme 8). The results show that spirocyclic 1,3‐oxathiolanes can be prepared from thiolactones with oxiranes. The nucleophilic attack of the thiocarbonyl S‐atom at the SiO2‐activated oxirane ring proceeds with high regio‐ and stereoselectivity via an SN2‐type mechanism.
Chiral Borate Esters in Asymmetric Synthesis. Part 2
Authors: Liu Dejun , Shan Zixing , Zhou Yan , Wu Xiaojun , Qin Jingui 
Published: September 2004

AbstractAsymmetric catalytic activity of the chiral spiroborate esters 1–9 with a O3BN framework (see Fig. 1) toward borane reduction of prochiral ketones was examined. In the presence of 0.1 equiv. of a chiral spiroborate ester, prochiral ketones were reduced by 0.6 equiv. of borane in THF to give (R)‐secondary alcohols in up to 92% ee and 98% isolated yields (Scheme 1). The stereoselectivity of the reductions depends on the constituents of the chiral spiroborate ester (Table 2) and the structure of the prochiral ketones (Table 1). The configuration of the products is independent of the chirality of the diol‐derived parts of the catalysts. A mechanism for the catalytic behavior of the chiral spiroborate esters (R,S)‐2 and (S,S)‐2 during the reduction is also suggested.
New Protected Protecting Groups for the 5′‐Hydroxy Group of Deoxynucleosides by Use of 2‐(Hydroxymethyl)‐ and 2‐[(Methylamino)methyl]benzoyl Skeletons and Oxidatively Cleavable Tritylthio and (4‐Methoxytrityl)thio Groups
Authors: Seio Kohji , Utagawa Eri , Sekine Mitsuo 
Published: September 2004

AbstractThe new protecting groups 1a,b and 2a,b were developed for the 5′‐OH group of deoxynucleosides by utilizing the unique characters of the sulfenate and sulfenamide linkage. These new protecting groups have a 2‐(hydroxymethyl)benzoyl or 2‐[(methylamino)methyl]benzoyl skeleton whose hydroxy O‐atom or amino N‐atom was blocked with a tritylthio‐type substituent. They are removable by intramolecular cyclization following the oxidative hydrolysis of the tritylthio‐type substituents under mildly oxidative conditions (Schemes 3 and 6). Among them, 2‐{{[(4‐methoxytrityl)sulfenyl]oxy}methyl}benzoyl (MOB; 2b) was found to be the most preferable for protection of the 5′‐OH function of deoxynucleosides. MOB can be introduced at the 5′‐OH groups of various deoxynucleosides without the protection of the 3′‐OH functions (Scheme 5). The applicability of the MOB group to a new oligodeoxynucleotide synthesis protocol without acid treatment was demonstrated by the solid‐phase synthesis of a tetrathymidylate (Scheme 8).
Inhibitors Designed for Presenilin 1 by Means of Aspartic Acid Activation. Preliminary Communication
Authors: Larbig Gregor , Zall Andrea , Schmidt Boris 
Published: September 2004

Abstractγ‐Secretase, a multiprotein aspartic protease crucial to Alzheimer's dementia, is not available for NMR experiments and has, so far, escaped crystallization. A positional scan of the aspartic protease by reactive probes may provide the necessary structural information for drug development. We describe here the synthesis of acid‐labile compounds based on the known inhibitor DAPT (1), e.g., the N‐terminally functionalized diazo compound 4 or the C‐terminally acid‐labile (cyclopropylmethyl)ester 11, which were designed to react in the specific acidic active‐site environment of the aspartic protease presenilin 1. The acid‐labile DAPT analogues 11–13, indeed, displayed strong inhibition in a cell‐free γ‐secretase assay.
Junceellonoids A and B, Two New Briarane Diterpenoids from the Chinese Gorgonian Junceella fragilisRidley
Authors: Zhang When , Guo Yue‐Wei , Mollo Ernesto , Cimino Guido 
Published: September 2004

AbstractTwo new diterpenoids, junceellonoids A and B (1 and 2, resp.), together with the seven known diterpenoids 3–9, all possessing the briarane carbon skeleton, were isolated from the gorgonian Junceella fragilis Ridley, collected in the South Sea of China. The structures and relative configurations of the new metabolites were elucidated based on extensive spectral analysis and by comparison with known spectral data.
Abietanes and a Novel 20‐Norabietanoid from Plectranthus cyaneus (Lamiaceae)
Authors: Horvath Tibor , Linden Anthony , Yoshizaki Fumihiko , Eugster Conrad Hans , Rüedi Peter 
Published: September 2004

AbstractAntioxidative‐activity‐guided fractionation of extracts of the aerial parts of the title plant yielded the two novel abietanoid diterpenoids 11,20‐dihydroxysugiol (=11,12,20‐trihydroxyabieta‐8,11,13‐trien‐7‐one; 3) and 1,11‐epoxy‐6,12‐dihydroxy‐20‐norabieta‐1(10),5,8,11,13‐pentaen‐7‐one (4) in addition to 11‐hydroxysugiol (=12‐O‐demethylcryptojaponol=11,12‐dihydroxyabieta‐8,11,13‐trien‐7‐one; 2) and the main constituent carnosolon (=6,20‐epoxy‐6,11,12‐trihydroxyabieta‐8,11,13‐trien‐7‐one; 1). The structures were established on the basis of spectroscopic, chiroptic, and X‐ray crystallographic evidence.
Versatile One‐Step One‐Pot Direct Aldol Condensation Promoted by MgI2
Authors: Wei Han‐Xun , Li Kunyu , Zhang Qian , Jasoni Richard L. , Hu Jiali , Paré Paul W. 
Published: September 2004

AbstractA true one‐step one‐pot aldol‐reaction procedure has been developed for the synthesis of β‐hydroxy ketones and esters. The reaction can be run at room temperature by simply mixing four components in CH2Cl2, with medium‐to‐high yields of aldol products obtained after regular workup. Mechanistically, the process probably proceeds via Mg‐enolate formation of the ketone or ester component, followed by addition to the electrophilic aldehyde.
Synthesis of Substituted α‐(Hydroxymethyl)‐β‐iodoacrylates via MgI2‐Promoted Stereoselective Aldol Coupling
Authors: Wei Han‐Xun , Hu Jiali , Jasoni Richard L. , Li Guigen , Paré Paul W. 
Published: September 2004

AbstractThe efficient and highly stereoselective syntheses of a variety of (Z)‐configured, substituted α‐(hydroxymethyl)‐β‐iodo‐acrylates from prop‐2‐ynoate and various aldehydes was achieved. The synthetic protocol involves a simple one‐pot coupling reaction under mild conditions, promoted by MgI2, which serves both as a Lewis acid and iodine source for a BaylisHillman‐type reaction. All adducts were generated in good‐to‐excellent yields, the (Z)‐isomers being formed in high selectivity (>98%). The conversion of methyl prop‐2‐ynoate into an active ‘β‐iodo allenolate’ intermediate, which then nucleophilically attacks an aldehyde, is proposed as a plausible reaction mechanism.
Cyclotrimerization of ‘Oxabenzonorbornadiene’: Synthesis of syn‐ and anti‐5,6,11,12,17,18‐Hexahydro‐5,18:6,11:12,17‐triepoxytrinaphthylene
Authors: De Lucchi Ottorino , Daştan Arif , Altundaş Aliye , Fabris Fabrizio , Balci Metin 
Published: September 2004

AbstractAn efficient synthetic route to the concave‐shaped, potentially ionophoric syn‐ and anti‐isomers of 5,6,11,12,17,18‐hexahydro‐5,18:6,11:12,17‐triepoxytrinaphthylene (4) was elaborated. Starting from ‘oxabenzonorbornadiene’ (5), the stannylated precursor 9 was prepared in three steps, followed by cyclotrimerization catalyzed by copper(I) thiophene‐2‐carboxylate (CuTC) , which afforded 4 in a syn/anti ratio of 5 : 4.
Circular‐Dichroism Studies on Artemisinin and Epiartemisinin and Their β‐Cyclodextrin Complexes in Solution
Authors: Marconi Giancarlo , Monti Sandra , Manoli Francesco , Degli Esposti Alessandra , Guerrini Andrea 
Published: September 2004

AbstractThe circular dichroism (CD) spectra of the powerful antimalarian active principle artemisinin (ART; 1) from Artemisia annua, and of epiartemisinin (EPI, 2), its C(7) epimer, were studied in solution in the presence and absence of β‐cyclodextrin (β‐cd). A significant inversion of sign in the region of the second electronic transition was detected. The rotational strengths were successfully calculated within the time‐dependent density functional theory (DFT), which enabled us to establish a correlation between the molecular recognition and the biological acitivities of the two isomers.