Hanaya, Kengo

写真a

Affiliation

Faculty of Pharmacy, Department of Pharmaceutical Sciences 有機薬化学講座 (Shiba-Kyoritsu)

Position

Assistant Professor/Senior Assistant Professor

Academic Degrees 【 Display / hide

  • 博士(薬学), Tokyo University of Science, Coursework, 2012.03

    Design and Synthesis of Biomedical Tools and Metalloprotease Inhibitors Based on Chemical Properties of 8-Quinolinol and Their Sulfonates

 

Papers 【 Display / hide

  • Unified short syntheses of oxygenated tricyclic aromatic diterpenes by radical cyclization with a photoredox catalyst

    Hashimoto R., Hanaya K., Sugai T., Higashibayashi S.

    Communications Chemistry (Communications Chemistry)  6 ( 1 )  2023.12

    Research paper (scientific journal), Joint Work, Accepted

     View Summary

    The biomimetic two-phase strategy employing polyene cyclization and subsequent oxidation/substitution is an effective approach for divergent syntheses of [6-6-6]-tricyclic diterpenes. However, this strategy requires lengthy sequences for syntheses of oxygenated tricyclic aromatic abietane/podocarpane diterpenes owing to the many linear oxidation/substitution steps after cyclization. Here, we present a new synthetic route based on a convergent reverse two-phase strategy employing a reverse radical cyclization approach, which enabled the unified short syntheses of four aromatic abietane/podocarpane diterpenes and the divergent short syntheses of other related diterpenes. Oxygenated and substituted precursors for cyclization were convergently prepared through Friedel-Crafts acylation and rhodium-catalyzed site-selective iodination. Radical redox cyclization using an iridium photoredox catalyst involving neophyl rearrangement furnished the thermodynamically favored 6-membered ring preferentially. (±)-5,6-Dehydrosugiol, salvinolone, crossogumerin A, and Δ5-nimbidiol were synthesized in only 8 steps. An oxygenated cyclized intermediate was also useful for divergent derivatization to sugiol, ferruginol, saprorthoquinone, cryptomeriololide, and salvinolone.

  • Synthesis and luminescence properties of substituted benzils

    Yasui M., Fujihara T., Ohtsu H., Wada Y., Shimada T., Zhu Y., Kawano M., Hanaya K., Sugai T., Higashibayashi S.

    Communications Chemistry (Communications Chemistry)  6 ( 1 )  2023.12

    Research paper (scientific journal), Accepted

     View Summary

    Photophysical properties of benzil (1,2-diphenylethane-1,2-dione) and its derivatives in the crystal state have recently attracted much attention. However, the study of substituted benzils has mostly been limited to para-substituted derivatives, which did not induce a significant effect on the emission wavelength compared to pristine benzil. The effects of ortho- and meta-substituents on the photophysical properties in the crystal state have not been investigated so far. Our recently developed organocatalytic pinacol coupling of substituted benzaldehydes allowed us to prepare various ortho-, meta-, and para-substituted benzil derivatives and to investigate their luminescence properties. Ortho- and meta-substituents affected the electronic states of benzils in the crystal state, resulting in differences in their luminescence properties. The luminescence wavelength and type, i.e., phosphorescence or fluorescence, were altered by these substituents. Fast self-recovering phosphorescence-to-phosphorescence mechanochromism by the para-CF3 substituent at room temperature was also discovered.

  • Selective modification of tryptophan in polypeptides via C-N coupling with azoles using in situ-generated iodine-based oxidants in aqueous media

    Watanabe S., Wada Y., Kawano M., Higashibayashi S., Sugai T., Hanaya K.

    Chemical Communications (Chemical Communications)  59 ( 87 ) 13026 - 13029 2023.10

    Research paper (scientific journal), Last author, Corresponding author, Accepted,  ISSN  13597345

     View Summary

    This study demonstrates the C-N coupling of tryptophan with azoles, promoted by an in situ-generated iodine-based oxidant. The protocol was successfully applied to the selective modification of tryptophan in nonprotected polypeptide bearing oxidatively sensitive residues in acidic aqueous media. The present method allows the attachment of reactive handles to polypeptides and the peptide stapling.

  • Inversion of Diaza[5]Helicenes Through an N−N Bond Breaking Pathway

    Kobayashi T., Ishiwari F., Fukushima T., Nojima Y., Hasegawa M., Mazaki Y., Hanaya K., Sugai T., Higashibayashi S.

    Chemistry - A European Journal (Chemistry - A European Journal)  29 ( 43 )  2023.08

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  09476539

     View Summary

    1,1’,10,10’-Biphenothiazine and its S,S,S’,S’-tetroxide are diaza[5]helicenes with N−N linkages. Kinetic experiments on racemization together with DFT calculations revealed that they undergo inversion through the N−N bond breaking pathway rather than the general conformational pathway. In these diaza[5]helicenes with this inversion mechanism, the reduction of electronic repulsion in the N−N bond by modification of S to SO2 at the outer position of the helix led to a significantly higher inversion barrier, 35.3 kcal/mol, compared to [5]helicene. 1,1’,10,10’-Biphenothiazine S,S,S’,S’-tetroxide was highly resistant to acid-mediated N−N bond breaking and racemization under acidic conditions.

  • Single-Step N-Terminal Modification of Proteins via a Bio-Inspired Copper(II)-Mediated Aldol Reaction

    Hanaya K., Yamoto K., Taguchi K., Matsumoto K., Higashibayashi S., Sugai T.

    Chemistry - A European Journal (Chemistry - A European Journal)  28 ( 47 )  2022.08

    Research paper (scientific journal), Lead author, Corresponding author, Accepted,  ISSN  09476539

     View Summary

    The chemical modification of proteins is an effective technique for manipulating the properties and functions of proteins, and for creating protein-based materials. The N-terminus is a promising target for single-site modification that provides modified proteins with uniform structures and properties. In this paper, a copper(II)-mediated aldol reaction with 2-pyridinecarboxaldehyde (2-PC) derivatives is proposed as an operationally simple method to selectively modify the N-terminus of peptides and proteins at room temperature and physiological pH. The copper(II) ion activates the N-terminal amino acids by complexation with an imine of the N-terminal amino acid and 2-PCs, realizing the selective formation of the nucleophilic intermediate at the N-terminus. This results in a stable carbon-carbon bond between the 2-PCs and the α-carbon of various N-terminal amino acids. The reaction is applied to four different proteins, including biopharmaceuticals such as filgrastim and trastuzumab. The modified trastuzumab retains the human epidermal growth factor receptor 2 recognition activity.

display all >>

Papers, etc., Registered in KOARA 【 Display / hide

Presentations 【 Display / hide

display all >>

Research Projects of Competitive Funds, etc. 【 Display / hide

  • 一時的配向基を用いた遷移金属触媒反応によるタンパク質ペプチド結合の化学修飾

    2021.04
    -
    2024.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

  • ボロン酸を用いるクロスカップリング反応を基盤としたタンパク質化学修飾法の開発

    2019.04
    -
    2021.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists , Principal investigator

  • スルホン酸エステルを母核とした刺激応答性リンカーの開発とプロドラッグへの応用

    2016.04
    -
    2019.03

    JAPAN SOCIETY FOR THE PROMOTION OF SCIENCE, Grant-in-Aid for Scientific Research, KENGO HANAYA, Research grant, No Setting

  • 刺激応答性リンカーの創製に向けたアミノスルホン酸エステルの分子内環化反応の開発

    2016.04
    -
    2017.03

    THE JAPAN SCIENCE SOCIETY, SASAKAWA SCIENTIFIC RESEARCH GRANT, KENGO HANAYA, Research grant, Principal investigator

  • 酵素触媒を活用した不斉誘導体化試薬の創製 (超高感度化と効率的供給法の開発)

    2015.04
    -
    2016.03

    日本私立学校振興・共済事業団, The Science Research Promotion Fund, Kengo Hanaya, Principal investigator

 

Courses Taught 【 Display / hide

  • STUDY OF MAJOR FIELD: (ORGANIC AND BIOCATALYTIC CHEMISTRY)

    2023

  • SEMINAR: (ORGANIC AND BIOCATALYTIC CHEMISTRY)

    2023

  • RESEARCH FOR BACHELOR'S THESIS 1

    2023

  • RESEARCH APPARATUS LABORATORY COURSE

    2023

  • PHARMACEUTICAL-ENGLISH SEMINAR

    2023

display all >>