東林　修平 (ヒガシバヤシ　シュウヘイ)

Higashibayashi, Shuhei

写真a

所属（所属キャンパス）

薬学部 薬科学科 有機薬化学講座 （芝共立）

職名

准教授
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  • 甲種危険物取扱者, 2004年08月

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研究分野 【 表示 ／ 非表示 】

  • 有機化学

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  • Synthesis of 5-Hydroxy-3′,4′,7-trimethoxyflavone and Related Compounds and Elucidation of Their Reversal Effects on BCRP/ABCG2-Mediated Anticancer Drug Resistance

    Tsunekawa R., Katayama K., Hanaya K., Higashibayashi S., Sugimoto Y., Sugai T.

    ChemBioChem （ChemBioChem)  20 （ 2 ） 210 - 220 2019年01月

    ISSN  14394227

    　概要を見る

    © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 3′,4′,7-Trimethoxyflavone (TMF) has been reported to show a potent reversal effect on drug resistance mediated by breast cancer resistance protein (BCRP)/ATP-binding cassette subfamily G member 2 (ABCG2). In this study, we designed and synthesized five derivatives with either a hydroxy group or a fluorine atom at C-5 and several kinds of capping moiety at the C-7 hydroxy group, on the same 3′,4′-dimethoxy-substituted flavone skeleton. We subsequently evaluated the efficacies of these compounds against BCRP-expressing human leukaemia K562/BCRP cells. Reversal of drug resistance was expressed as the concentration of compound causing a twofold reduction in drug sensitivity (RI 50 ). Of the synthesized compounds, the reversal effect of 5-hydroxy-3′,4′,7-trimethoxyflavone (HTMF, RI 50 7.2 nm) towards 7-ethyl-10-hydroxycamptothecin (SN-38) was stronger than that of TMF (RI 50 18 nm). Fluoro-substituted 5-fluoro-3′,4′,7-trimethoxyflavone (FTMF, RI 50 25 nm) and monoglycosylated 7-(β-glucosyloxy)-5-hydroxy-3′,4′-dimethoxyflavone (GOHDMF, 91 nm) also exhibited reversal effects, whereas the di- and triglycoside derivatives did not. TMF, HTMF and FTMF at 0.01–10 μm upregulated the K562/BCRP cellular accumulation of Hoechst 33342 nuclear staining dye. In addition, western blotting revealed that treatment of K562/BCRP cells with 0.1 μm TMF, HTMF or FTMT suppressed the expression of BCRP. HTMF showed the strongest inhibition of BCRP-mediated efflux and suppression of BCRP expression of the three effective synthesized flavones.

  • Site-selective synthesis of acacetin and genkwanin through lipase-catalyzed deacetylation of apigenin 5,7-diacetate and subsequent methylation

    Fujita R., Mandal S., Hanaya K., Shoji M., Higashibayashi S., Sugai T.

    Heterocycles （Heterocycles)  99 （ 1 ） 638 - 648 2019年

    ISSN  03855414

    　概要を見る

    © 2019 The Japan Institute of Heterocyclic Chemistry. Candida antarctica lipase B-catalyzed deacetylation proceeded with high site-selectivity on the C-4′ acetyl group in apigenin triacetate to give apigenin 5,7-diacetate. Methylation of the liberated hydroxy group with the combination of trimethyloxonium tetrafluoroborate (Meerwein reagent) and 1,8-bis(dimethylamino)naphthalene (proton sponge) in CH2Cl2 proceeded in a quantitative manner to give the product methylated at the C-4′ hydroxy group (acacetin 5,7-diacetate). Even with the same precursor, a different methylation product at the C-7 hydroxy group (genkwanin 4′,5-diacetate) was obtained in 86% yield by applying iodomethane and Cs2CO3 in dimethyl sulfoxide (DMSO). The methylated products were deprotected to form acacetin and genkwanin. We inferred that the latter unexpected methylation was ascribable to the intermolecular migration of an acetyl group from C-7 to C-4′. DFT calculations indicated that the C-7 phenoxide ion was 12.6 kJ/mol more stable than the initially formed C-4′ phenoxide ion.

  • Lipase-catalyzed site-selective deacetylation of sterically hindered naphthohydroquinone diacetate and its application to the synthesis of a heterocyclic natural product

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

    Heterocycles （Heterocycles)  99 （ 1 ） 625 - 632 2019年

    ISSN  03855414

    　概要を見る

    © 2019 The Japan Institute of Heterocyclic Chemistry. Lipase-catalyzed site-selective deacetylation of 2,5-dimethylnaphthalene-l,4-diol diacetate was examined. With Candida antarctica lipase B, the suppressing effect of a methyl substituent at the peri-position of the a-naphthyl ester over that at the ortho-position was significant. This site-selectivity was in contrast to that of chemical hydrolysis reported to date. From the resulting monoacetate, mansonone F, a physiologically active heterocyclic orthoquinone, was synthesized in 38% yield in as few as three steps.

  • Chemoenzymatic synthesis of hydroxytyrosol monoesters and their suppression effect on nitric oxide production stimulated by lipopolysaccharides

    Sakakura A., Pauze M., Namiki A., Funakoshi-Tago M., Tamura H., Hanaya K., Higashibayashi S., Sugai T.

    Bioscience, Biotechnology and Biochemistry （Bioscience, Biotechnology and Biochemistry)  83 （ 2 ） 185 - 191 2019年

    ISSN  09168451

    　概要を見る

    © 2018 Japan Society for Bioscience, Biotechnology, and Agrochemistry. Fatty acid monoesters of hydroxytyrosol [2-(3,4-dihydroxyphenyl)ethanol] were synthesized in two steps from tyrosol (4-hydroxyphenylethanol) by successive Candida antarctica lipase B-catalyzed chemoselective acylation on the primary aliphatic hydroxy group over phenolic hydroxy group in tyrosol, and 2-iodoxybenzoic acid (IBX)-mediated hydroxylation adjacent to the remaining free phenolic hydroxy group. Examination of their suppression effects on nitric oxide production stimulated by lipopolysaccharides in RAW264.7 cells showed that hydroxytyrosol butyrate exhibited the highest inhibition (IC 50 7.0 μM) among the tested compounds.

  • Dearomative Oxidative Rearrangement of [3]Cyclo-1,8-carbazolylene

    Yasui M., Ohtsu H., Kawano M., Hanaya K., Sugai T., Higashibayashi S.

    Chemistry Letters （Chemistry Letters)  47 （ 11 ） 1357 - 1359 2018年11月

    研究論文（学術雑誌）,  ISSN  0366-7022

    　概要を見る

    © 2018 The Chemical Society of Japan. [3]Cyclo-1,8-carbazolylene was found to undergo oxidative rearrangement by oxidation with 2,3-dichloro-5,6-dicyano-pbenzoquinone, giving a 9a-substituted carbazol-1-one derivative. This is the first example of a dearomative oxidative rearrangement of a carbazole or aniline derivative. The geometrical and electronic structures were elucidated by X-ray analysis, UV-vis absorption spectroscopy, and DFT calculations.

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  • 生物活性物質合成に有用な、リパーゼが触媒する位置・官能基選択的反応

    須貝 威、橋本 理一、坂倉 彩香、藤田 理愛、花屋 賢悟、東林 修平

    日本農芸化学会2019年度大会, 2019年03月, 口頭（一般）

  • 配糖体糖鎖の効率よい加水分解を利用した希少フラボノイドの合成研究

    倉林一樹, 花屋賢悟, 東林修平, 須貝威

    日本薬学会第139年会 (幕張) , 2019年03月, ポスター（一般）

  • BCRPを介した3’,4’-ジメトキシフラボン類の抗がん剤耐性克服作用

    恒川龍二, 片山和浩, 花屋賢悟, 東林修平, 杉本芳一,　須貝 威

    日本薬学会第139年会 (幕張) , 2019年03月, ポスター（一般）

  • 1,3-ジカルボニル化合物の不斉還元における Chiralscreen® OH の有効性

    奥山雅洋, 恒川龍二, 渡邉俊佑, 桑田和明, 永井利也, 花屋賢悟, 東林修平, 須貝威

    第20回生体触媒化学シンポジウム (東工大すずかけ台キャンパス) , 2018年12月, ポスター（一般）

  • Lipase-catalyzed site-selective deacetylation of sterically hindered polyphenol acetates and its application to the synthesis of bioactive natural products

    Lipase-catalyzed site-selective deacetylation of sterically hindered polyphenol acetates and its application to the synthesis of bioactive natural products

    第20回生体触媒化学シンポジウム (東工大すずかけ台キャンパス) , 2018年12月, 口頭（招待・特別）

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競争的資金等の研究課題 【 表示 ／ 非表示 】

  • ジグザグ型ヘテロカーボンナノベルトの合成

    2017年06月
    -
    2019年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 東林　修平, 挑戦的研究(萌芽), 補助金,  代表

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受賞 【 表示 ／ 非表示 】

  • 有機合成化学奨励賞

    2012年, 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年, 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年, 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年, 非環状天然有機化合物の立体配置決定法Universal NMR Databaseの開発

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担当授業科目 【 表示 ／ 非表示 】

  • 課題研究（有機薬化学）

    2019年度

  • 演習（有機薬化学）

    2019年度

  • 卒業研究Ｃ

    2019年度

  • 卒業研究Ａ

    2019年度

  • 薬学英語演習Ｅ

    2019年度

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