Higashibayashi, Shuhei



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


Associate Professor

Licenses and Qualifications 【 Display / hide

  • 甲種危険物取扱者, 2004.08


Research Areas 【 Display / hide

  • Organic chemistry


Books 【 Display / hide

  • Kinetic Control in Synthesis and Self-Assembly

    Shuhei Higashibayashi (Ed. M Numata, S. Yagai, T. Hamura), Elsevier, 2018

    Scope: Chapter 4, “Control of Inversion Kinetics of Bowl-Shaped Aromatic Compounds”,  Contact page: 65-96

  • Polycyclic Arenes and Heteroarenes: Synthesis, Properties, and Applications

    Shuhei Higashibayashi, Hidehiro Sakurai, etc. (Ed. Q. Miao), Wiely-VCH, 2015

    Scope: Chapter 3, "Growing Buckybowl Chemistry",  Contact page: 61-84

  • Chemical Science of π-Electron Systems

    Shuhei Higashibayashi, Hidehiro Sakurai, etc. (Eds. T. Akasaka, A. Osuka, S. Fukuzumi, H. Kandori, Y. Aso), Springer, 2015

    Scope: Chapter 6, "Chiral Sumanene, Triazasumanene, and Related Buckybowls",  Contact page: 91-106

  • CSJカレントレビュー, 未来材料を創出するπ電子系の科学

    櫻井英博, 東林修平, 他, 化学同人, 2013

    Scope: 第1章 精密合成が拓くπ電子科学,  Contact page: 46-53

  • 使える!有機合成反応241実践ガイド

    櫻井英博, 東林修平, 他(丸岡啓二, 野崎京子, 石井康敬, 大寺純蔵, 富岡清編著), 化学同人, 2010

    Contact page: 86-87

Papers 【 Display / hide

  • Analysis of Interconversion between Atropisomers of Chiral Substituted 9,9’-Bicarbazole

    Kobayashi T., Ishiwari F., Fukushima T., Hanaya K., Sugai T., Higashibayashi S.

    European Journal of Organic Chemistry 2021 ( 3 ) 449 - 451 2021.01

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  1434193X

     View Summary

    © 2020 Wiley-VCH GmbH Interconversion of atropisomers of chiral 3,3’-di-tert-butyl-9,9’-bicarbazole linked by a single N−N bond was analyzed by DFT calculations and experiments. The calculations revealed that the trans transition state has a lower energy for the interconversion than the cis transition state. The lowest transition state of interconversion between natural dixiamycins A and B containing a 9,9’-bicarbazole structure was found to be the trans transition state. The calculations also indicated that degradation through N−N bond cleavage was faster than racemization. Atropisomeric enantiomers of 3,3’-di-tert-butyl-9,9’-bicarbazole were resolved by chiral HPLC for the first time, and then racemization and N−N bond cleavage were investigated by heating experiments, showing that racemization did not take place below the degradation temperature.

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

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

    ChemistryOpen  2021

    Research paper (scientific journal), Joint Work, Accepted

     View Summary

    © 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.

  • 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 84 ( 8 ) 1554 - 1559 2020.08

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  09168451

     View Summary

    © 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 84 ( 7 ) 1339 - 1344 2020.07

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  09168451

     View Summary

    © 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.

  • Stepwise approach for sterically hindered Csp3-Csp3 bond formation by dehydrogenative: O -alkylation and Lewis acid-catalyzed [1,3]-rearrangement towards the arylalkylcyclopentane skeleton of sesquiterpenes

    Fujitani B., Hanaya K., Sugai T., Higashibayashi S.

    Chemical Communications 56 ( 25 ) 3621 - 3624 2020.03

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  13597345

     View Summary

    This journal is © The Royal Society of Chemistry. A stepwise dehydrogenative cross-coupling method was developed for the formation of sterically hindered Csp3-Csp3 bonds. Intramolecular dehydrogenative O-alkylation of a β-ketoester by 2,3-dichloro-5,6-dicyano-p-benzoquinone to form an oxolane followed by Lewis acid-catalyzed [1,3]-rearrangement furnished the sesquiterpene arylmethylcyclopentane skeleton. The formal syntheses of herbertane-type β-herbertenol, cuparane-type enokipodins A and B were also achieved.

display all >>

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

Reviews, Commentaries, etc. 【 Display / hide

  • Recent examples of the use of biocatalysts with high accessibility and availability in natural product synthesis

    Takeshi Sugai, Shuhei Higashibayashi, Kengo Hanaya

    Tetrahedron  74   3469 - 3487 2018

    Introduction and explanation (scientific journal), Joint Work

  • Synthesis of Sumanene and Related Buckybowls

    huhei Higashibayashi, Hidehiro Sakurai

    Chemistry Letters 40   122 - 128 2011

    Introduction and explanation (scientific journal), Joint Work

  • おわん型共役炭素化合物バッキーボウルの合成


    有機合成化学協会誌 67   38 - 50 2009

    Introduction and explanation (scientific journal), Single Work

Presentations 【 Display / hide

  • 第四級炭素を有するセスキテルペン類の骨格合成を志向した脱水素的O-ベンジル化-ルイス酸触媒[1,3]-転位シーケンスによるCsp3-Csp3結合形成

    藤谷万, 花屋賢悟, 須貝威, 東林修平

    第78回有機合成化学協会関東支部シンポジウム (新潟) , 2019.11, Oral Presentation(general)

  • Acid-responsieve helical heterocycles with embedded hydrazine

    Higashibayashi S.

    The 4th Joint Conference Keio & Kaohsiung Medical University (Kaohsiung Medical University) , 2019.09, Oral Presentation(guest/special)

  • Development of oxidative C-C bond formation between phenols and alkenes

    Deguchi H., Hanaya K., Sugai T., Higashibayashi S.

    The 4th Joint Conference Keio & Kaohsiung Medical University (Kaohsiung Medical University) , 2019.09, Oral Presentation(general)

  • 三次元ヘテロπ電子系分子の創製


    分子研シンポジウム2019 (分子科学研究所) , 2019.06, Oral Presentation(guest/special), 分子科学研究所

  • 3-カルバモイル-2,4-ジニトロフェニルピリジニウムのDiels-Alder反応に関する計算化学的考察

    中原正貴, 花屋賢悟, 須貝威, 東林修平

    第115回有機合成化学シンポジウム (仙台) , 2019.06, Poster (general)

display all >>

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

  • 酸化的芳香族-アルケンカップリングの開発と展開


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 東林 修平, Grant-in-Aid for Scientific Research (C), Principal Investigator

  • ジグザグ型ヘテロカーボンナノベルトの合成


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 東林 修平, Grant-in-Aid for Challenging Research (Exploratory) , Principal Investigator

Awards 【 Display / hide

  • 有機合成化学奨励賞

    2012, おわん型π共役分子バッキーボウルの合成

  • 日本化学会第90春季年会「若い世代の特別講演会」

    2010, C3対称バッキーボウルの液相合成法の開発

  • 日本化学会第87春季年会優秀講演賞

    2007, キラルバッキーボウルの合成研究

  • 天然物化学談話会奨励賞

    2005, 非環状天然有機化合物の立体配置決定法Universal NMR Databaseの開発


Courses Taught 【 Display / hide











display all >>


Memberships in Academic Societies 【 Display / hide

  • 日本薬学会

  • 日本化学会

  • 有機合成化学協会

  • 基礎有機化学会