有機合成化学協会誌
Online ISSN : 1883-6526
Print ISSN : 0037-9980
ISSN-L : 0037-9980
最新号
Special Issue in English
選択された号の論文の11件中1~11を表示しています
Preface
Accounts
  • 伊藤 寛晃, 井上 将行
    2021 年 79 巻 11 号 p. 996-1004
    発行日: 2021/11/01
    公開日: 2021/11/10
    ジャーナル オープンアクセス

    Natural products have been valuable starting points for drug discovery. In this account, we describe a new high-throughput strategy for the functional enhancement and alteration of antibacterial, peptidic natural products. Our strategy integrates solid-phase peptide synthesis, a one-bead-one-compound approach for structural randomization, a microscale bioassay for the selection of hit compounds, and tandem mass spectrometry for structural determination. First, the antibacterial activity of the macrocyclic peptide lysocin E (1) was enhanced. A total of 2401 randomized analogues were synthesized and subjected to two assays to discover more active analogues 3-5. Second, the relative activities of gramicidin A (2) against bacteria and mammalian cells were altered. A total of 4096 randomized analogues were prepared, and their biological activities were evaluated by three assays, revealing that analogues B01 and B12 had comparable antibacterial activity but displayed significantly attenuated mammalian cytotoxicity. These results together demonstrated the efficiency of the newly designed strategy for the optimization of desirable features as pharmaceuticals in a short time frame.

  • 長尾 一哲, 大宮 寛久
    2021 年 79 巻 11 号 p. 1005-1012
    発行日: 2021/11/01
    公開日: 2021/11/10
    ジャーナル オープンアクセス

    Carbocations have gained much attention as fundamental and reactive chemical species, enabling the construction of sterically hindered and complex molecules. Conventionally, the generation of a carbocation requires the use of strong acid, which limits their applications to the synthesis of highly functionalized molecules. Herein, we present a visible light-mediated, organophotoredox, radical-polar crossover catalytic method for non-acidic generation of carbocations. Under blue light irradiation, a phenothiazine based- organophotoredox catalyst converts an alkyl electrophile to the corresponding alkylsulfonium species via sequential single electron transfer events. The generated alkylsulfonium species acts as a carbocation equivalent, and reacts with a broad range of nucleophiles. By taking advantage of the characteristics of radical-mediated reactions, a radical relay type, vicinal difunctionalization of alkenes has also been accomplished.

  • 樫田 啓, 浅沼 浩之
    2021 年 79 巻 11 号 p. 1013-1019
    発行日: 2021/11/01
    公開日: 2021/11/10
    ジャーナル オープンアクセス

    Natural base pairs stabilize nucleic acid duplexes via hydrogen bonding and stacking interactions, and efforts have been made to identify artificial base pairs that stabilize duplexes through different interactions. Herein, we describe our attempts to prepare pseudo base pairs that exhibit high stability and orthogonality. Pairs of azobenzene derivatives showed unexpectedly high stability and orthogonality due to intermolecular stacking interactions. Pairs of cationic molecules showed even higher stability than natural G-C pairs through both electrostatic and stacking interactions. Duplexes can be crosslinked via [2+2] photocycloaddition between stilbene derivatives, and pairs of non-planar cyclohexane derivatives can stabilize duplexes by hydrophobic interactions rather than stacking interactions. Hetero-selective pairing can be achieved using electron donor-acceptor interactions. These pseudo base pairs would work well as building blocks in nanotechnology and biotechnology due to their unique functionalities.

  • 小和田 俊行, 水上 進
    2021 年 79 巻 11 号 p. 1020-1032
    発行日: 2021/11/01
    公開日: 2021/11/10
    ジャーナル オープンアクセス

    Recent studies have revealed that some intracellular metal ions other than Ca 2+ also act as signaling mediators. Detailed analyses of such intracellular metal ion dynamics will enhance our understanding of the physiological roles of these metal ions. Fluorescence imaging is a powerful technique for this purpose owing to its high spatiotemporal resolution. However, with respect to metal ion selectivity, subcellular localization, and robustness to intracellular environmental changes, there are not yet enough fluorescent metal-ion probes suitable for such intracellular analysis. Recently, we have developed several metal ion probes that combine the characteristics of small-molecule fluorescent probes, such as ease of tuning of fluorescence properties and metal ion affinities, with subcellular localizability by a tag protein. In this account, we introduce our recent achievements in the development of small molecule-protein hybrid fluorescent probes and their applications such as long-term imaging of intracellular Mg 2+ dynamics and quantification of labile Zn 2+ concentration in the Golgi apparatus.

  • 村岡 貴博
    2021 年 79 巻 11 号 p. 1033-1040
    発行日: 2021/11/01
    公開日: 2021/11/10
    ジャーナル オープンアクセス

    Fibrous aggregates of polypeptides linked by β-sheet assemblies are important supramolecular morphologies in biology, chemistry and materials science. β-Sheet-forming synthetic amphiphilic peptides afford hydrogels that have been used as biomaterials for cell culturing and differentiation media. For their bio-related applications, tuning the mechanical and biological properties of the amphiphilic peptides is critically important, and this has mainly been done by modulating the side chain structures. In this review, the effects of flexible alkylene chains inserted in the interior sequence of amphiphilic peptides on supramolecular morphologies and biological properties are described. Exchange of glycine for alanine residues influences the self-assembling structures and mechanical properties depending on the sites substituted. Despite increased conformational flexibility due to the alanine-to-glycine substitution, insertion of glycine at the center of the peptide molecule forms a hydrogel with enhanced mechanical stiffness. Extending the length of the central alkylene chains further enhanced the stiffness of hydrogel. Furthermore, insertion of an alkylene chain in the peptide backbone allows the endowment of dynamic properties such as thermal gel-to-sol transition, while the cell adhesive properties are reduced on insertion of relatively long alkylene chains. The versatility of alkylene-chain insertion into a polypeptide main chain for tuning, chemical, physical and biological properties is reported.

  • 江木 晃人, 田中 宏昌, 吉澤 一成
    2021 年 79 巻 11 号 p. 1041-1049
    発行日: 2021/11/01
    公開日: 2021/11/10
    ジャーナル オープンアクセス

    Catalytic nitrogen fixation reactions using metal complexes have been developed both experimentally and theoretically. In particular, the catalytic activity of the system using dinitrogen-bridging dimolybdenum complexes as reaction intermediates is significant. The Mo-NN-Mo core structure in the dimolybdenum complex plays an important role in the catalytic reaction. In this account, the role of the Mo-NN-Mo structure of the dinuclear molybdenum complex is explained qualitatively in terms of the orbital interaction. A catalytic cycle including the dimolybdenum intermediates obtained from density functional theory (DFT) calculations is also presented.

  • 西野 智雄, Colin J. Martin, 安原 主馬, Gwénaël Rapenne
    2021 年 79 巻 11 号 p. 1050-1055
    発行日: 2021/11/01
    公開日: 2021/11/10
    ジャーナル オープンアクセス

    In this account, we describe our achievements in the field of technomimetic synthetic nanovehicles from the first synthetic nanovehicle, a wheelbarrow with two wheels, to the nanocar which qualified for the 2nd Nanocar Race. The architecture of these nanovehicles is based on a polyaromatic or phorphyrinic chassis with ethynyltriptycenyl moiety used as wheels. The rigid and planar chassis also provides us with a potential cargo platform able to transport atoms or small molecules on surfaces.

  • 金城 玲
    2021 年 79 巻 11 号 p. 1056-1064
    発行日: 2021/11/01
    公開日: 2021/11/10
    ジャーナル オープンアクセス

    The concept of aromaticity has been of paramount significance in myriad fields of chemistry. To modulate the intrinsic electronic nature of aromatic molecules, partial incorporation of heteroatoms into the benzene scaffold represents a useful strategy in modern inorganic chemistry. This account presents how to incorporate boron into aromatic six-membered scaffolds, leading to hybrid organic/inorganic benzenes, namely diazadiborinines. In addition, their reactivity towards a variety of substrates are summarized.

  • 和佐 雅幸, Ahmet Yesilcimen
    2021 年 79 巻 11 号 p. 1065-1072
    発行日: 2021/11/01
    公開日: 2021/11/10
    ジャーナル オープンアクセス

    Cooperative actions of two or more Lewis acid and/or Lewis base catalysts can be exploited to promote enantioselective transformations that are not readily achieved by a single catalyst system. Nonetheless, undesirable acid-base complexation which occurs in a reaction mixture containing the catalysts, substrates, and products often results in poor reaction efficiency and a contrived substrate scope. In this article, we highlight our development of multi-catalyst systems that facilitate enantioselective transformations of otherwise unreactive C-H bonds contained in various carbonyl compounds and N-alkylamines while overcoming the formation of inert Lewis adducts. Such methods were achieved through the identification of catalyst/substrate combinations that form frustrated Lewis pairs (FLPs), namely, highly active acids and bases whose mutual quenching is precluded due to steric and electronic factors.

Lounge
  • 村上 正浩, 田中 一義
    2021 年 79 巻 11 号 p. 1073-1076
    発行日: 2021/11/01
    公開日: 2021/11/10
    ジャーナル オープンアクセス

    Three methods which explain a bimolecular nucleophilic substitution reaction are discussed: (i) A traditional method using curved arrows provides a facile means for depicting how valence electrons move and are redistributed during the reaction. (ii) A method based on the orbital interaction theory deals with two independent orbitals of the two isolated reactants, one occupied and the other unoccupied. The energy gained by their stabilizing interaction is considered to assist the two reactants in surmounting the energy barrier of the substitution reaction. (iii) A method inspecting a set of molecular orbitals of a composite molecule that consists of the two reactants can describe any point on the reaction path. According to the last method, the reactant state, the intermediate states including the transition state, and the product state can be correlated with continuity. Although the methods (ii) and (iii) both deal with molecular orbitals, what they illuminate are different. Whereas the method (ii) based on the orbital interaction theory tractably predicts a driving force which arises only near the reactant state from the static viewpoint, the whole entire course of the reaction ought to be described by the method (iii), with which the ever-changing behaviors of the molecular orbitals are trailed along the reaction path. The present example on the simplest reaction course sounds a caution that chemists cannot be too careful about giving an interpretation based on the simple orbital interaction theory to the results obtained by calculations on a composite molecule with the whole reaction path being viewed.

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