bluuebunny/crossref_metadata_2025_split huggingface dataset:
Total Synthesis of Laulimalide: Assembly of the Fragments and Completion of the Synthesis of the Natural Product and a Potent Analogue
Authors: Trost Barry M. , Amans Dominique , Seganish W. Michael , Chung Cheol K. 
Published: February 2012

AbstractHerein, we present a full account of our efforts to couple the northern and the southern building blocks, the synthesis of which were described in the preceding paper, along with the modifications required to ultimately lead to a successful synthesis of laulimalide. Key highlights include an exceptionally efficient and atom‐economical intramolecular ruthenium‐catalyzed alkene–alkyne coupling to build the macrocycle, followed by a highly stereoselective 1,3‐allylic isomerization promoted by a rhenium complex. Interestingly, the designed synthetic route also allowed us to prepare an analogue of the natural product that possesses significant cytotoxic activity. We also report a second generation route that provides a more concise synthesis of the natural product.
Dipeptidyl Peptidase IV (DPPIV/CD26)‐Based Prodrugs of Hydroxy‐Containing Drugs
Authors: Diez‐Torrubia Alberto , Cabrera Silvia , Lambeir Anne‐Marie , Balzarini Jan , Camarasa María‐José , Velázquez Sonsoles 
Published: February 2012

AbstractWe previously described a novel prodrug approach in which a di‐ or tetrapeptide moiety is linked to a wide variety of amine‐containing drugs through an amide bond, which is specifically cleaved by dipeptidyl peptidase IV (DPPIV/CD26) activity. Herein we report the application of this prodrug approach to a variety of hydroxy‐containing drugs (primary, secondary, tertiary, or aromatic hydroxy groups). We designed and studied tripartite prodrugs containing a dipeptide moiety (cleavable by DPPIV/CD26) and a valine as a hetero‐bifunctional connector to link the dipeptide to the hydroxy group of the drug through a metabolically labile ester bond. The hydroxy‐containing prodrugs showed various susceptibilities to hydrolysis by DPPIV/CD26 and serum, depending on the nature of the compound. Prodrugs of compounds containing a primary hydroxy group (as in didanosine) or a hydroxy moiety on an aromatic entity (as in acetaminophen) were most efficiently converted. In contrast, a tertiary hydroxy group was much less susceptible to conversion into its parent drug by DPPIV/CD26 or serum. A number of the prodrugs showed remarkable increases in water solubility relative to their parent drugs.
Discovery of [(2R,5R)‐5‐{[(5‐Fluoropyridin‐2‐yl)oxy]methyl}‐2‐methylpiperidin‐1‐yl][5‐methyl‐2‐(pyrimidin‐2‐yl)phenyl]methanone (MK‐6096): A Dual Orexin Receptor Antagonist with Potent Sleep‐Promoting Properties
Authors: Coleman Paul J. , Schreier John D. , Cox Christopher D. , Breslin Michael J. , Whitman David B. , Bogusky Michael J. , McGaughey Georgia B. , Bednar Rodney A. , Lemaire Wei , Doran Scott M. , Fox Steven V. , Garson Susan L. , Gotter Anthony L. , Harrell C. Meacham , Reiss Duane R. , Cabalu Tamara D. , Cui Donghui , Prueksaritanont Thomayant , Stevens Joanne , Tannenbaum Pamela L. , Ball Richard G. , Stellabott Joyce , Young Steven D. , Hartman George D. , Winrow Christopher J. , Renger John J. 
Published: February 2012

AbstractInsomnia is a common disorder that can be comorbid with other physical and psychological illnesses. Traditional management of insomnia relies on general central nervous system (CNS) suppression using GABA modulators. Many of these agents fail to meet patient needs with respect to sleep onset, maintenance, and next‐day residual effects and have issues related to tolerance, memory disturbances, and balance. Orexin neuropeptides are central regulators of wakefulness, and orexin antagonism has been identified as a novel mechanism for treating insomnia with clinical proof of concept. Herein we describe the discovery of a series of α‐methylpiperidine carboxamide dual orexin 1 and orexin 2 receptor (OX1R/OX2R) antagonists (DORAs). The design of these molecules was inspired by earlier work from this laboratory in understanding preferred conformational properties for potent orexin receptor binding. Minimization of 1,3‐allylic strain interactions was used as a design principle to synthesize 2,5‐disubstituted piperidine carboxamides with axially oriented substituents including DORA 28. DORA 28 (MK‐6096) has exceptional in vivo activity in preclinical sleep models, and has advanced into phase II clinical trials for the treatment of insomnia.
A DDS‐based middleware for quality‐of‐service and high‐performance networked robotics
Authors: Cruz Jesús Martínez , Romero‐Garcés Adrián , Rubio Juan Pedro Bandera , Robles Rebeca Marfil , Rubio Antonio Bandera 
Published: February 2012

SUMMARYSocial robots must adapt to dynamic environments, human interaction partners and challenging new stringent tasks. Their inner software is usually distributed and should be designed and deployed carefully because slight changes in the robot's requirements can have an important impact not only on the existing source code but also on the resulting performance at run‐time. This paper proposes an implementation of this inner software using a new lightweight middleware for networked robotics called Nerve. The principal novelty this middleware has with respect to other state‐of‐the‐art approaches is that it guarantees both scalability and QoS, which are key requirements for real‐time robotics software. The benefits of Nerve have been proved through its use in two key components of the cognitive system of a social robot: (i) the visual attention mechanism, used to extract relevant data from perceived images; and (ii) a robot learning by imitation control architecture that allows the social robot to be taught by people using natural demonstrations (i.e. using the same communication channels that would be used to teach people). Nerve makes use of existing patterns for networked applications together with the recent Data Distribution Service specification, which is a publish/subscribe standard for real‐time and distributed systems that provides a wide set of QoS policies. In this paper, these different QoS policies have been applied carefully to achieve the best performance of the target robot. Copyright © 2012 John Wiley & Sons, Ltd.
One‐Dimensional 3d–3d–4f Trimetallic Assemblies Consisting of CuII2LnIII Trinuclear Complexes and Hexacyanometallate
Authors: Shiga Takuya , Mishima Akio , Sugimoto Kunihisa , Ōkawa Hisashi , Oshio Hiroki , Ohba Masaaki 
Published: February 2012

AbstractA series of one‐dimensional heterotrimetallic assemblies, [Cu2Ln(L)2(H2O)4][M(CN)6]·nH2O [Ln = Gd, M = Co (1), Fe (2), Cr (3), and Ln = La, M = Co (4), Fe (5), Cr (6)], were prepared by the reaction of a Cu2Ln precursor complex, [Cu2Ln(L)2(NO3)3], with K3[M(CN)6] in water. All of the assemblies were isomorphous and formed a 1D zigzag chain, in which the [Cu2Ln(L)2(H2O)4]3+ and [M(CN)6]3– units were alternately positioned and were linked in a Cu–NC–M–CN–Cu manner. Compound 1 showed magnetic behaviour similar to that of the discrete precursor complex, [Cu2Gd(L)2(NO3)3], owing to the diamagnetic nature of the [CoIII(CN)6]3– unit. In the case of 2, a simple summation of the magnetic behaviour of the [Cu2Gd(L)2(H2O)4]3+ and [Fe(CN)6]3– units was observed, whereas ferromagnetic interactions were found to be operative between the Cu2+ and Cr3+ ions in compound 3. The same magnetic interactions between Cu2+ and M3+ were confirmed in compounds 4 to 6, which included the diamagnetic La3+ ion. The differences in the magnetic behaviours of 2 and 3 can be explained by the overlap of the d(Cu)–pπ(CN) orbitals in the bent Cu–N≡C linkage and the spin‐density on the cyanide nitrogen of the [Cr(CN)6]3– unit.
Synthesis of Oligomeric Zinc Complexes with Bicyclic and Acyclic Guanidinate Ligands
Authors: Neuhäuser Christiane , Reinmuth Matthias , Kaifer Elisabeth , Himmel Hans‐Jörg 
Published: February 2012

AbstractZinc dichloride and dimethylzinc were treated with several acyclic and bicyclic guanidines. Three different bicyclic guanidines and their potassium guanidinate salts were treated with ZnCl2. The reaction with the neutral guanidines afforded mononuclear complexes, stabilized by intramolecular hydrogen bonding. The reaction with the potassium guanidinate salts led to trinuclear complexes, which were extremely water sensitive. The reaction in the presence of added water furnished a tetranuclear complex with a central OZn4 unit in good yield, to which six guanidinate ligands were bound. The reaction of dimethylzinc with 2‐[N,N′‐diisopropylguanidino]pyridine and 2‐[N,N′‐diisopropylguanidino]quinoline afforded di‐ and tetranuclear Zn methyl complexes with mono‐ and dianionic guanidinate ligands. Dinuclear complexes of the monoanionic guanidinate ligands were formed at room temperature. At higher temperatures (75 °C), complete deprotonation of the guanidino groups and formation of tetranuclear Zn alkyl complexes was observed, which feature low‐coordinate zinc sites.
Coordinating Properties of Pyrone and Pyridinone Derivatives, Tropolone and Catechol toward the VO2+ Ion: An Experimental and Computational Approach
Authors: Sanna Daniele , Buglyó Péter , Bíró Linda , Micera Giovanni , Garribba Eugenio 
Published: February 2012

AbstractThe interaction of the VO2+ ion with pyrone derivatives and tropolone, which form very effective antidiabetic compounds, is critically re‐examined. The binary systems with ethylmaltol (Hema) and tropolone (Htrop) were studied in aqueous solution and in the solid state through the combined application of spectroscopic (EPR, UV/Vis and IR) and pH‐potentiometric techniques. The results were compared with those of the systems with maltol (Hma) and kojic acid (Hkoj) and rationalized on the basis of DFT simulations. All the ligands L– form [VOL]+, cis‐[VOL2(H2O)] and cis‐[VOL2(OH)]– species in aqueous solutions and a square‐pyramidal [VOL2] complex in the solid state, which transforms into cis‐[VOL2(solvent)] when it is dissolved in water or in a coordinating solvent. The coordinating properties of the ligands studied were compared with those of pyridinone [3‐hydroxy‐1,2‐dimethyl‐4(1H)pyridinone (Hdhp), and 1,2‐diethyl‐3‐hydroxy‐4(1H)pyridinone (Hdepp)] derivatives and catechol (H2cat), and were explained by postulating that from pyrones to pyridinones and to catechol the donor set changes progressively from (CO, O–) to (O–, O–). DFT calculations allowed us to determine the relative stability of the four possible structures (square pyramidal, trans‐ and two cis‐octahedral) of the bis‐chelated species and the aromaticity of the protonated, neutral and deprotonated form of the ligands through the calculation of the HOMA (harmonic oscillator model of aromaticity) index. The relationship between the electric charge on the oxygen donors, the mean distances and the difference between the lengths of C–Oket and C–Ophen bonds with (i) the pKa of the ligands, (ii) the pK of deprotonation of the equatorially coordinated water molecule in cis‐[VOL2(H2O)], and (iii) the 51V hyperfine coupling constant (Az) of [VOL2], cis‐[VOL2(H2O)] and cis‐[VOL2(OH)]– was also found and discussed.
Molecular Structure of a Hydridoniobocene Complex [Nb(η5‐C5H4SiMe3)2(H)3] and Its Use as Catalyst for the Ring‐Opening Polymerization of Cyclic Esters
Authors: Alonso‐Moreno Carlos , Antiñolo Antonio , García‐Martínez Joaquín C. , García‐Yuste Santiago , López‐Solera Isabel , Otero Antonio , Pérez‐Flores Juan C. , Tercero‐Morales Maria T. 
Published: February 2012

AbstractThe second polyhydridoniobocene complex that was characterized by X‐ray diffraction is reported. On the basis of H–H distances and H–Nb–H angles, [Nb(η5‐C5H4SiMe3)2(H)3] (1) is classified as a “compressed hydride”. Compound 1 acts as an efficient single‐component initiator for the ring‐opening polymerization of ϵ‐caprolactone and δ‐valerolactone. ϵ‐Caprolactone and δ‐valerolactone are both polymerized within a few hours to yield high‐to‐medium‐molecular‐weight polymers with medium to broad polydispersities. Polymer end‐group analysis showed that the polymerization proceeds through a coordination–insertion mechanism based on the cleavage of the ring between the oxygen atom and the acyl carbon atom.
Structure–Relaxivity Relationships among Targeted MR Contrast Agents
Authors: Caravan Peter , Zhang Zhaoda 
Published: February 2012

AbstractParamagnetic gadolinium(III) complexes are widely used to increase contrast in magnetic resonance (MR) images. Contrast enhancement depends on the concentration of the gadolinium complex and on its relaxivity, an inherent property of the complex. Increased relaxivity results in greater image contrast or the ability to detect the contrast agent at a lower concentration. An increase in the relaxivity enables the imaging of abundant molecular targets. Relaxivity depends on the structure of the complex, kinetics of inner‐sphere and second‐sphere water exchange, and on the rotational dynamics of the molecule. The latter, and in some cases the former, properties of the complex change when it is bound to its target. All of these properties can be rationally tuned to enhance relaxivity. In this Microreview, we summarize our efforts in understanding and optimizing the relaxivity of contrast agents targeted to serum albumin and to fibrin.
Activation of Gas‐Phase Uranyl Diacetone Alcohol Coordination Complexes by Spectator Ligand Addition
Authors: Rios Daniel , Gibson John K. 
Published: February 2012

AbstractGas‐phase addition of a basic ligand to dipositive uranyl coordination complexes comprising diacetone alcohol (DAA) results in water‐elimination, which indicates aldol dehydration of DAA to produce mesityl oxide. A novel attribute of the observed gas‐phase chemistry is that a ligand exothermically associates to a coordination complex to provide the excitation required to induce chemistry in other ligands, with the added “spectator ligand” remaining intact in the product. Dehydration of DAA was observed for addition of tetrahydrofuran, acetone, and 2‐propanol to uranyl complexes [UO2(DAA)2]2+ and [UO2(DAA)(acetone)2]2+. In contrast, [UO2(DAA)2(acetone)]2+ did not exhibit ligand‐addition chemistry, which is attributed to a high degree of coordinative saturation at the uranium metal center.
Preparation of New 1,4‐Diazocanes as Scaffolds for Combinatorial Chemistry
Authors: Penning Miriam , Christoffers Jens 
Published: February 2012

AbstractHexahydro‐2‐oxo‐1,4‐diazocin‐6‐carboxylic acid constitutes a conformationally rigid, crown‐shaped scaffold. An orthogonally protected (Boc at N‐4 and methyl ester at 6‐CO2H) representative was prepared by ring expansion of a 3‐pyrrolidone‐derived 1,4‐diketone with MeNH2. After deprotection, this building block was further diversified by reductive aminations and amidations and by sulfonamide and urea formation. Furthermore, the 6‐CO2H function was transformed into a 6‐NHCbz group in one step by carboxamide degradation in the presence of BnOH. An example of a cyclic tripeptoidic structure was synthesized by amidation with N‐Boc‐β‐alanine and glycine methyl ester. Structural features of the eight‐membered heterocycle were established by single‐crystal X‐ray structure analysis of a 4‐bromoaniline derivative.
Total Synthesis of (+)‐Aspicilin by an Alkyne‐Based Approach and Its Biological Evaluation
Authors: Raji Reddy Chada , Rao Nagavaram Narsimha , Sujitha Pombala , Kumar Chityal Ganesh 
Published: February 2012

AbstractThe stereoselective total synthesis of (+)‐aspicilin is described. The pivotal step in this approach is the generation of an enyne intermediate by the coupling of an alkyne with vinyl iodide, which constructed the C6–C7 bond. Conversion of the enyne to the desired macrolide was achieved through Sharpless asymmetric dihydroxylation and Yamaguchi macrolactonization as the key steps. Additionally, the biological activity of (+)‐aspicilin was evaluated on A549, HeLa, and MCF7 cancer cell lines.
Synthesis of Modified Phenylalanine Peptides by Cross Enyne Metathesis and a Diels–Alder Reaction as Key Steps
Authors: Kotha Sambasivarao , Goyal (née Bansal) Deepti , Thota Niranjan , Srinivas Venu 
Published: February 2012

AbstractModified phenylalanine‐based di‐ and tripeptides have been efficiently assembled by cross enyne metathesis and a Diels–Alder reaction as key steps under mild conditions. In all cases, peptide integrity was preserved, no racemisation was observed, and good yields of modified peptides were obtained.
Ti/Ni‐Based Multimetallic System for the Efficient Allylation of Carbonyl Compounds
Authors: Martínez‐Peragón Ángela , Millán Alba , Campaña Araceli G. , Rodríguez‐Márquez Irene , Resa Sandra , Miguel Delia , Álvarez de Cienfuegos Luis , Cuerva Juan M. 
Published: February 2012

AbstractA mild method for the allylation of carbonyl compounds is presented. This methodology allows the allylation of a broad range of carbonyl compounds starting with allyl carbonates as pronucleophiles. Noteworthy is that ketones, infrequent substrates in other related protocols, are suitable substrates under these reaction conditions. Moreover, the reaction proceeds at room temperature with the use of catalytic amounts of both Ni and Ti catalysts. The success of this strategy is based on the perfect match between the late transition metal (nickel) and the radical reagent (titanium). The use of Ni instead of Pd widens the scope of this transformation and makes this method more economical.
A polymorphism in a let‐7 microRNA binding site of KRAS in women with endometriosis
Authors: Grechukhina Olga , Petracco Rafaella , Popkhadze Shota , Massasa Efi , Paranjape Trupti , Chan Elcie , Flores Idhaliz , Weidhaas Joanne B. , Taylor Hugh S. 
Published: February 2012

AbstractEndometriosis is found in 5–15% of women of reproductive age and is more frequent in relatives of women with the disease. Activation of KRAS results in de novo endometriosis in mice, however, activating KRAS mutations have not been identified in women. We screened 150 women with endometriosis for a polymorphism in a let‐7 microRNA (miRNA) binding site in the 3'‐UTR of KRAS and detected a KRAS variant allele in 31% of women with endometriosis as opposed to 5% of a large diverse control population. KRAS mRNA and protein expression were increased in cultured endometrial stromal cells of women with the KRAS variant. Increased KRAS protein was due to altered miRNA binding as demonstrated in reporter assays. Endometrial stromal cells from women with the KRAS variant showed increased proliferation and invasion. In a murine model, endometrial xenografts containing the KRAS variant demonstrated increased proliferation and decreased progesterone receptor levels. These findings suggest that an inherited polymorphism of a let‐7 miRNA binding site in KRAS leads to abnormal endometrial growth and endometriosis. The LCS6 polymorphism is the first described genetic marker of endometriosis risk.
Influence of Attitudes towards Change and Self‐directness on Dropout in Eating Disorders: A 2‐Year Follow‐up Study
Authors: Rodríguez‐Cano Teresa , Beato‐Fernandez Luis , Moreno Luis Rojo , Vaz Leal Francisco J. 
Published: February 2012

AbstractObjectiveThis study examined dropout‐related factors at the Outpatient Eating Disorders Treatment Programme.MethodOne hundred ninety‐six eating disorders patients following DSM‐IV diagnostic criteria that consecutively commenced treatment were recruited and followed up for a 2‐year period. A total of 151 patients completed the whole assessment with a set of questionnaires evaluating eating and general psychopathology. The Attitudes towards Change in Eating Disorders questionnaire was used, and personality was evaluated using the Temperament and Character Inventory. During the follow‐up period, patients were re‐assessed. Two years later, 102 patients continued on treatment.ResultsScores on Precontemplation at the beginning were predictors for dropout at 2‐year follow‐up. Character variables, as Responsibility, Integrity and Self‐acceptance were protective factors to be at Precontemplation stage.DiscussionThe clinician's challenge is to help eating disorders patients to develop an unyielding sense of responsibility and self‐acceptance, aimed to integrate the therapeutic choice into their own intrapersonal frame of goals. Copyright © 2012 John Wiley & Sons, Ltd and Eating Disorders Association.
European Miocene Hominids and the Origin of the African Ape and Human Clade
Authors: Begun David R. , Nargolwalla Mariam C. , Kordos László 
Published: February 2012

AbstractIn 1871, Darwin famously opined, “In each great region of the world the living mammals are closely related to the extinct species of the same region. It is therefore probable that Africa was formerly inhabited by extinct apes closely allied to the gorilla and chimpanzee; and as these two species are now man's nearest allies, it is somewhat more probable that our early progenitors lived on the African continent than elsewhere.”1 Although this quote is frequently recalled today, Darwin's next line is rarely acknowledged: “But it is useless to speculate on this subject, for an ape nearly as large as a man, namely the Dryopithecus of Lartet, which was closely allied to the anthropomorphous Hylobates, existed in Europe during the Upper Miocene period; and since so remote a period the earth has certainly undergone many great revolutions, and there has been ample time for migration on the largest scale.”1
Somatic mutations in the notch, NF‐KB, PIK3CA, and hedgehog pathways in human breast cancers
Authors: Jiao Xiang , Wood Laura D. , Lindman Monica , Jones Sian , Buckhaults Phillip , Polyak Kornelia , Sukumar Saraswati , Carter Hannah , Kim Dewey , Karchin Rachel , Sjöblom Tobias 
Published: February 2012

AbstractExome sequencing of human breast cancers has revealed a substantial number of candidate cancer genes with recurring but infrequent somatic mutations. To determine more accurately their mutation prevalence, we performed a mutation analysis of 36 novel candidate cancer genes in 96 human breast cancers. Somatic mutations with potential impact on protein function were observed in the genes ADAM12, CENTB1, CENTG1, DIP2C, GLI1, GRIN2D, HDLBP, IKBKB, KPNA5, NFKB1, NOTCH1, and OTOF. These findings strengthen the evidence for involvement of the Notch, Hedgehog, NF‐KB, and PIK3CA pathways in breast cancer development, and point to novel processes that likely are involved. © 2012 Wiley Periodicals, Inc.