Hanaya, Kengo



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


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

  • Theoretical Analysis of the Heterocyclic [4+2] Cycloaddition Between Pyridinium Ion and Enol Ether

    Nakahara M., Hanaya K., Sugai T., Higashibayashi S.

    ChemistryOpen (ChemistryOpen)   2021

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    © 2021 The Authors. Published by Wiley-VCH GmbH Dearomative heterocyclic [4+2] cycloaddition between the N-(2,4-dinitrophenyl)pyridinium ion of nicotinamide and an enol ether was analyzed by Density Functional Theory (DFT) calculations. The calculation revealed that the reaction undergoes stepwise bond formation rather than occurring in a concerted manner. The experimental products were found to be both kinetically and thermodynamically favored. The calculated transition states and intermediate suggested that the high diastereoselectivity is derived from the electrostatic interaction between the 2-nitro group of the pyridinium ion and the hydrogen of the enol ether.

  • Nickel(II)‐Mediated C‐S Cross‐Coupling Between Thiols and ortho‐Substituted Arylboronic Acid

    Kengo Hanaya, Hiroyoshi Ohtsu, Masaki Kawano, Shuhei Higashibayashi, Takeshi Sugai

    Asian Journal of Organic Chemistry (Wiley)   2020.12

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  21935807

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    © 2020 Wiley-VCH GmbH Herein, we report a C−S cross-coupling reaction between alkyl thiols or aryl thiols and ortho-substituted arylboronic acids that proceeds in the presence of an inexpensive and ligand-free NiCl2 ⋅ 6H2O salt and N-methylmorpholine, a weak base, at 25 °C in air. The presence of coordinating and electron-withdrawing groups at the ortho-position of the arylboronic acids played a crucial role in determining the efficiency of the reaction. X-ray crystallographic analysis revealed that the [NiCl2(DMF)2(H2O)2] complex was formed in-situ. The complex is an excellent precursor of the active nickel species. The reaction offers an extremely mild and operationally convenient method to access a wide variety of alkyl aryl sulfides and diaryl sulfides without using expensive transition metals, such as palladium, gold, and rhodium, and specialized and expensive ligands.

  • Copper-mediated peptide arylation selective for the N-terminus

    Mary K. Miller, Haopei Wang, Kengo Hanaya, Olivia Zhang, Alex Berlaga and Zachary T. Ball

    Chemical Science (ROYAL SOCIETY OF CHEMISTRY)  11 ( 38 ) 10501 - 10505 2020.09

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  20416520

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    © The Royal Society of Chemistry 2020. Polypeptides present remarkable selectivity challenges for chemical methods. Amino groups are ubiquitous in polypeptide structure, yet few paradigms exist for reactivity and selectivity in arylation of amine groups. This communication describes the utilization of boronic acid reagents bearing certaino-electron withdrawing groups for copper-mediated amine arylation of the N-terminus under mild conditions and primarily aqueous solvent. The method adds to the toolkit of boronic acid reagents for polypeptide modification under mild conditions in water that shows complete selectivity for the N-terminus in the presence of lysine side chains.

  • Improved preparation of vitexin from hot water extract of Basella alba, the commercially available vegetable Malabar spinach (“Tsurumurasaki” in Japanese) and the application to semisynthesis of chafuroside B

    Kurahayashi K., Hanaya K., Higashibayashi S., Sugai T.

    Bioscience, Biotechnology and Biochemistry (Bioscience, Biotechnology and Biochemistry)  84 ( 8 ) 1554 - 1559 2020.08

    ISSN  09168451

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    © 2020, © 2020 Japan Society for Bioscience, Biotechnology, and Agrochemistry. Hot water extraction of D-arabinofuranosylvitexin from the raw leaves of commercially available Basella alba “Tsurumurasaki” and subsequent acidic hydrolysis was improved to be a procedure using a high-pressure steam sterilizer to afford vitexin. The amount was estimated to be 14.1 mg from 1 g of dry weight of the raw leaves, whose recovery was calculated to be 95% based on the estimated content of D-arabinofuranosylvitexin in B. alba raw leaves. The product was dehydratively cyclized between hydroxy groups on the carbohydrate and flavone skeletons under modified Mitsunobu reaction conditions in N,N-dimethylformamide to give chafuroside B, which is known to be a bioactive Oolong tea polyphenol. Through these transformations, 10.2 mg of chafuroside B could be semisynthesized from 1 g of dry weight of the raw leaves, and the efficiency was improved compared to that from the extraction from Oolong tea (3.4 μg from 1 g of dry weight).

  • Comprehensive semisyntheses of catathelasmols C, D, and E from D-glutamic acid, utilizing lipase-catalyzed site-selective reactions on intermediates

    Hashiba R., Hashimoto R., Nishiguchi M., Kobayashi T., Hanaya K., Higashibayashi S., Sugai T.

    Bioscience, Biotechnology and Biochemistry (Bioscience, Biotechnology and Biochemistry)  84 ( 7 ) 1339 - 1344 2020.07

    ISSN  09168451

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    © 2020, © 2020 Japan Society for Bioscience, Biotechnology, and Agrochemistry. Catathelasmols C, D, and E, which had been isolated from Catathelasma imperiale as inhibitors for 11-hydroxysteroid dehydrogenases, were comprehensively semisynthesized from commercially available D-glutamic acid. The key synthetic intermediate, (R)-pentane-1,2,5-triol, was site-selectively acetylated by treatment with vinyl acetate and Candida antarctica lipase B (Novozym 435) in tetrahydrofuran (THF) at 25°C to furnish 1,5-diacetate (catathelasmol E, quantitative). The acetylation occurred site-selectively on the primary alcohols at the C-1 and C-5 positions over the secondary alcohol at the C-2 position. Dichromic acid oxidation provided 2-oxopentane-1,5-diyl diacetate (catathelasmol C, 78%). Burkholderia cepacia lipase-catalyzed transesterification with methanol in THF at–5°C proceeded preferentially on the acetate at C-1 located adjacent to the C-2 carbonyl group over the other terminal acetate at the C-5 position. 5-Hydroxy-4-oxopentyl acetate (catathelasmol D) was obtained in 53% yield.

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

Presentations 【 Display / hide

  • ボロン酸を活用した生体高分子の化学修飾


    2019年度若手研究者のためのセミナー, 2019.08, Public discourse, seminar, tutorial, course, lecture and others

  • Nickel(II)-mediated arylation of biopolymers with arylboronic acid

    Kengo Hanaya, Mary K. Miller, Jun Ohata, Alicia E. Mangubat-Medina, Zachary T. Ball

    ISABC 2019 — 15th International Symposium on Applied Bioinorganic Chemistry, 2019.06, Oral Presentation(general)

  • ニッケル触媒を用いたシステイン選択的アリール化反応

    花屋 賢悟, 大畠 潤, Mary K. MILLER, Alicia E. MANGUBAT-MEDINA, Zachary T. BALL

    日本薬学会 第139年会, 2019.03, Oral Presentation(general)

  • Selective chemical protein modification with nickel(II) and arylboronic acid

    Kengo Hanaya, Jun Ohata, Mary K. Miller, Alicia E. Mangubat-Medina, Zachary T. Ball

    日本化学会 第99春季年会, 2019.03, Oral Presentation(general)

  • Development of enzyme-activatable sulfonate-based prodrugs for active targeting therapy

    SASAKI Akio, SHOJI Mitsuru, SUGAI Takeshi, HANAYA Kengo

    ICC05-AEM2016, 2016.09, Poster (general)

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

  • 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


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 花屋 賢悟, 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


    JAPAN SOCIETY FOR THE PROMOTION OF SCIENCE, Grant-in-Aid for Scientific Research, KENGO HANAYA, Research grant

  • 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



  • 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)


    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











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