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

  • 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

  • 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

  • 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

  • Chemoenzymatic semisynthesis of caffeic acid β-phenethyl ester, an antioxidative component in propolis, from raw coffee bean extract

    Hashimoto R., Iai H., Fujita R., Hanaya K., Higashibayashi S., Inoue H., Sugai T.

    Bioscience, biotechnology, and biochemistry 85 ( 3 ) 476 - 480 2021.02

    Research paper (scientific journal), Joint Work, Accepted

     View Summary

    © The Author(s) 2020. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry. Caffeic acid β-phenethyl ester (CAPE), an antioxidative bioactive catechol isolated from propolis, was semisynthesized from chlorogenic acid and related compounds in an extract of raw (unroasted) Robusta coffee (Coffea canephora) beans in 5 steps and a total yield of 31%. Oxidative degradation of the intermediates and target molecule was prevented by alkaline hydrolysis of the chlorogenic acids in the presence of sodium dithionite (Na2S2O4) and deprotection of the catecholic diacetate precursor by Candida antarctica lipase B-mediated transesterification as the final step.

  • 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.

  • Semisynthesis of prunetin, a bioactive O-methylated isoflavone from naringenin, by the sequential deacetylation of chalcone intermediates and oxidative rearrangement

    Sugai T., Hanaya K., Higashibayashi S.

    Bioscience, biotechnology, and biochemistry 85 ( 1 ) 143 - 147 2021.01

    Research paper (scientific journal), Joint Work, Accepted

     View Summary

    © The Author(s) 2021. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry. Prunetin (4',5-dihydroxy-7-methoxyisoflavone) was semisynthesized in 8 steps from readily available naringenin in 26% total yield. The key reaction was chemoenzymatic sequential deacetylation to 6'-acetoxy-2',4″-dihydroxy-4'-methoxychalcone, the in situ-formed precursor for thallium(III) nitrate-mediated oxidative rearrangement.

  • A Concise Total Synthesis of Dehydroantofine and Its Antimalarial Activity against Chloroquine-Resistant Plasmodium falciparum

    Yamasaki N., Iwasaki I., Sakumi K., Hokari R., Ishiyama A., Iwatsuki M., Nakahara M., Higashibayashi S., Sugai T., Imagawa H., Kubo M., Fukuyama Y., Ōmura S., Yamamoto H.

    Chemistry - A European Journal 27   5555 - 5563 2021

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

     View Summary

    © 2021 Wiley-VCH GmbH The total synthesis of dehydroantofine was achieved by employing a novel, regioselective, azahetero Diels–Alder reaction of easily accessible 3,5-dichloro-2H-1,4-oxazin-2-one with 14 a as a key step. Furthermore, it is demonstrated that dehydroantofine is a promising candidate as a new antimalarial agent in a biological assay with chloroquine-resistant Plasmodium falciparum.

  • 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.

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

  • シンビオイミンの全合成を志向した、官能基選択性非依存的なヒドロキノリン構築法の開拓


    日本薬学会第141年会 (広島(オンライン開催)) , 2021.03, Oral Presentation(general)

  • 天然より豊富に得られるアラビノシルビテキシンを出発原料としたチャフロシドBの調製


    日本薬学会第141年会 (広島(オンライン開催)) , 2021.03, Poster (general)

  • フェノールとアルケン類の分子内酸化的芳香族求核置換反応の開発(2)


    日本薬学会第141年会 (広島(オンライン開催)) , 2021.03, Oral Presentation(general)

  • フェノールの位置選択的水酸化と新規1,2-転位によるカテコール類の合成手法の開拓


    日本薬学会第141年会 (広島(オンライン開催)) , 2021.03, Oral Presentation(general)

  • 置換カルバゾール二量体の窒素-窒素結合に由来する軸不斉における熱安定性の解明


    日本化学会第101春季年会 (オンライン開催) , 2021.03, 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