(±)-Aspidospermidineの全合成およびβ-シリルケトンを用いた新規反応

13301甲第4061号博士（薬学）金沢大学博士論文要旨Abstract 要約Outline 以下に掲載予定：Angewandte Chemie International Edition 53 Wiley 共著者：Mizuki Kawano,Aya Nowaki, Jun-ichi Matsu

Formal [4+2] cycloaddition of cyclobutanones bearing alkyne-cobalt complex at their 3-positions

Cyclobutanones bearing an alkyne-cobalt complex at their 3-positions reacted with aldehydes to give formal [4+2] cycloadducts by using tin(IV) chloride as a Lewis acid. Highly substituted tetrahydropyrone derivatives were stereoselectively prepared by this method. © 2011 Elsevier Ltd. All rights reserved

Resonant inelastic x-ray scattering study of hole-doped manganites La1-xSrxMnO3 (x=0.2 and 0.4)

Electronic excitations near the Fermi energy in the hole doped manganese oxides (La1-xSrxMnO3, x=0.2 and 0.4) have been elucidated by using the resonant inelastic x-ray scattering (RIXS) method. A doping effect in the strongly correlated electron systems has been observed for the first time. The scattering spectra show that a salient peak appears in low energies indicating the persistence of the Mott gap. At the same time, the energy gap is partly filled by doping holes and the energy of the spectral weight shifts toward lower energies. The excitation spectra show little change in the momentum space as is in undoped LaMnO3, but the scattering intensities in the low energy excitations of x=0.2 are anisotropic as well as temperature dependent, which indicates a reminiscence of the orbital nature

Ring cleavage and successive aldol reaction of 3-[(Trialkylsilyl)methyl] cyclobutanones

3-[(Trialkylsilyl)methyl]cyclobutanones reacted with aldehydes by activation with titanium(IV) chloride to give acyclic β,γ;- unsaturated β′-hydroxyketones. © 2011 American Chemical Society

An efficient procedure for preparation of 2-monoalkyl or 2-monoaryl-3-ethoxycyclobutanones

金沢大学医薬保健研究域薬学系Optimized reaction conditions for the preparation of various 2-monosubstituted 3-ethoxycyclobutanones are described. 2-Monoalkyl 3-ethoxycyclobutanones were efficiently prepared by the reaction of the corresponding carboxylic acid chlorides and an excess amount of ethyl vinyl ether in the presence of diisopropylethylamine at 90 °C in a sealed tube. 2-Monoaryl 3-ethoxycyclobutanones were prepared by using 2,6-lutidine as a base in the above-mentioned procedure. © 2010 Published by Elsevier Ltd. All rights reserved

Ring cleavage and successive aldol reaction of 3-[(Trialkylsilyl)methyl] cyclobutanones

3-[(Trialkylsilyl)methyl]cyclobutanones reacted with aldehydes by activation with titanium(IV) chloride to give acyclic β,γ;- unsaturated β′-hydroxyketones. © 2011 American Chemical Society

Dysregulated Aire expression and autoimmunity

Deficiency for AIRE/Aire in both humans and mice results in the development of organ-specific autoimmune disease. We tested whether augmented and/or dysregulated AIRE/Aire expression might be also prone to the breakdown of self-tolerance. To define the effect of augmented Aire expression on the development of autoimmunity, antigen-specific clonal deletion and production of clonotypic regulatory T cells (Tregs) in the thymus were examined using mice expressing two additional copies of Aire in a heterozygous state (3xAire-knockin mice: 3xAire-KI). We found that both clonal deletion of autoreactive T cells and production of clonotypic Tregs in the thymus from 3xAire-KI were impaired in a T-cell receptor-transgenic system. Furthermore, 3xAire-KI females showed higher scores of experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein than wild-type littermates, suggesting that augmented Aire expression exacerbates organ-specific autoimmunity under disease-prone conditions. In humans, we found that one patient with amyopathic dermatomyositis showed CD3–CD19– cells expressing AIRE in the peripheral blood before the treatment but not during the remission phase treated with immunosuppressive drugs. Thus, not only loss of function of AIRE/Aire but also augmented and/or dysregulated expression of AIRE/Aire should be considered for the pathogenesis of organ-specific autoimmunity. We suggest that further analyses should be pursued to establish a novel link between organ-specific autoimmune disease and dysregulated AIRE expression in clinical settings

BioHackathon series in 2011 and 2012: penetration of ontology and linked data in life science domains

The application of semantic technologies to the integration of biological data and the interoperability of bioinformatics analysis and visualization tools has been the common theme of a series of annual BioHackathons hosted in Japan for the past five years. Here we provide a review of the activities and outcomes from the BioHackathons held in 2011 in Kyoto and 2012 in Toyama. In order to efficiently implement semantic technologies in the life sciences, participants formed various sub-groups and worked on the following topics: Resource Description Framework (RDF) models for specific domains, text mining of the literature, ontology development, essential metadata for biological databases, platforms to enable efficient Semantic Web technology development and interoperability, and the development of applications for Semantic Web data. In this review, we briefly introduce the themes covered by these sub-groups. The observations made, conclusions drawn, and software development projects that emerged from these activities are discussed