人と環境に優しい有機合成反応の開発を目的とし，医薬品開発に必要な光学活性有機分子の合成研究に取り組んでいます。

教員(役職:氏名 / 学位)

	教授：三浦 剛（薬学博士）
	准教授：平島 真一　博士（薬学）
	講師：中島 康介　博士（薬学）
	助手：松島 恭征　学士

大学院生：3名（博士課程）
6年生:11名 (実験研究コース 9名、調査研究コース 2名）
5年生:8名 (実験研究コース 8名、調査研究コース 0名）
4年生:9名 (実験研究コース 9名、調査研究コース 0名）

詳細はこちら

(2024年4月現在)

(科目: 学年【前・後期】 /教員名)
講義科目
有機化学Ⅰ：第一学年【後期】/三浦剛、平島真一
有機化学Ⅱ：第二学年【前期】/三浦剛、平島真一
医療薬物薬学特論 I　創薬概論：第四学年【前期】/三浦剛　他
医療薬物薬学演習 I　医薬品創製と基礎（物理系・化学系）：第四学年【前期】/平島真一、中島康介
 
実習
化学系実習Ⅰ（基礎有機化学実習）：第一学年【後期】/三浦剛，平島真一，中島康介，松島恭征
化学系実習 II（有機化学実習）：第二学年【前期】/三浦剛，平島真一，中島康介，松島恭征
化学系実習Ⅲ（医薬品合成実習）：第三学年【前期】/三浦剛，平島真一，中島康介，松島恭征
 
卒論教室指導
科別英語特論Ⅰ：第四学年【前期】/三浦剛，平島真一，中島康介，松島恭征
科別英語特論Ⅱ：第五学年【通年】/三浦剛，平島真一，中島康介，松島恭征
課題研究（実験・調査研究コース）：第四、五、六学年【通年】/三浦剛，平島真一，中島康介，松島恭征
 
大学院
創薬有機化学特論：大学院薬科学研究科【前期】/三浦剛，平島真一
医化学特論：大学院薬学研究科博士課程【前期】/三浦剛，平島真一

1) 　近年，環境に優しく経済的な有機合成反応の開発が求められています。有機触媒は金属触媒と比較して毒性は低く，取扱いも容易であり，創薬プロセスにおける環境負荷低減型の方法論として注目を集めています。薬化学教室では，環境に優しい有機触媒を用いた不斉反応の開発研究に取り組み，より効率的な有機触媒の開発を目指します。さらに，得られた合成中間体を基に生理活性化合物の合成に展開します。
 
2) 　環境に優しい有機合成反応開発のアプローチとして，環境汚染に繋がる有機溶媒を使用せずに，無害で安価な水を反応溶媒として利用できる反応開発に取り組んでいます。
 
3) 　通常の有機触媒は反応で使用した後に廃棄されます。当研究室では、多量のフッ素を導入した触媒を調製することによって，高価な触媒を回収リサイクル使用できる経済的で環境調和型の反応開発研究にも取り組んでいます。
 
4) 　環境に優しい合成法とは如何に効率良く合成できるかという意味でもあります。効率良い合成、すなわち短工程かつ触媒反応の実現は有機化学の分野において重要な課題であります。そこで、当研究室では機能性化合物の新規効率合成法の開発とその機能性探索も行っています。

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“Synthesis of 2-Substituted Indoles via Migration Reaction of 3-Substituted Indoles with Triflic Acid”
K. Nakashima , Y. Kudo, Y. Matsushima, S. Hirashima, T. Miura,
Chem. Pharm. Bull. 72, 336–339, (2024).

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“Regioselective One-Pot Synthesis of Vicinal Bisphosphine Derivatives from Nitroalkenes by Hydrophosphinylation/ Elimination/Hydrophosphinylation”
E. Hirota, S. Hirashima,* R. Morita, J. Takase, Y. Matsushima, K. Nakashima, H. Akutsu, T. Miura,
Org. Lett. 26, 1797-1802, (2024).

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“Organocatalyzed Synthesis of Bicyclic γ-Lactam Derivatives via Asymmetric Conjugate Addition of Cyclic β-Keto Esters to Benzoyl Acrylonitriles”
Y. Matsushima, S. Kubokawa, M. Watanabe, K. Nakashima, S. Hirashima, T. Miura,
Asian J. Org. Chem. 13, href="https://onlinelibrary.wiley.com/doi/10.1002/ajoc.202300620">e202300620, (2024).

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“Vicinal All-Carbon Quaternary Stereocenter Construction with Trifluoromethyl Groups via Organocatalytic Asymmetric Cascade Michael/Michael Reaction”
R. Tsuyusaki, K. Nakashima, Y. Matsushima, S. Hirashima, T. Miura,
Chem. Asian. J. 18, e202300931, (2023).

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“Fluorescent Rotary Switches: Four- vs Three-Substituted Phthalimide Boron Difluoride Schiff Base Complexes”
D. Yordanov, R. Smolka, K. Nakashima, S. Hirashima, Y. Matsushima, M. Vala, J. Krajčovič, M. Weiter, T. Miura, A. Georgiev,
J. Org. Chem. xx, xxxxx, (2023).

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“Catalytic Synthesis of Phthalide Derivatives via Asymmetric Bromolactonization of Stilbene-type Carboxylic Acids using N,N- Dibenzyl Diaminomethylenemalononitrile as Organocatalyst”
Y. Matsushima, S. Fukuda, Y. Kobayashi, H. Nezu, K. Nakashima, S. Hirashima, T. Miura,
Asian J. Org. Chem. 12, e202300254, (2023).

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“Control over rotary motion and multicolour switching in 3-hydroxyphthalimide fluorophores: An interplay between AIE and ESIPT”
R. Smolka, D. Yordanov, K. Nakashima, M. Vala, J. Krajčovič, M. Weiter, A. Georgiev,
Dyes and Pigments 215, 111279, (2023).

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“Asymmetric Direct Vinylogous Conjugate Addition of α,β-Unsaturated γ-Butyrolactam to Acyl Acrylonitriles using Organocatalysts”
D. Ishii, S. Hirashima, K. Nakashima, Y. Matsushima, T. Sakai, H. Akutsu, T. Miura,
Asian J. Org. Chem. e202300082, (2023).

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“Highly efficient, asymmetric, and organocatalyst-based Henry reactions between α,β-unsaturated trifluoromethyl ketone and nitromethane”
R. Tsuyusaki, K. Nakashima, M. Shimomura, M. Kawada, Y. Matsushima, S. Hirashima, T. Miura,
Tetrahedron Lett. 117, 154375, (2023).

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“Synthesis of Chiral α-Substituted β-Aminophosphine Derivatives through Asymmetric Hydrophosphinylation Utilizing Secondary Phosphine Sulfides”
S. Hirashima, E. Hirota, Y. Matsushima, N. Noda, Y. Nishimura, T. Narushima, K. Nakashima, T. Miura,
Chem. Asian J. e202200989, (2022).

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“Asymmetric Friedel−Crafts Alkylation of Indoles with α,β-unsaturated Trifluoromethyl Ketones Using a Squaramide Organocatalyst”
K. Nakashima, S. Hanamura, A. Imamura, Y. Matsushima, S. Hirashima, T. Miura,
Asian J. Org. Chem. e202200403, (2022).

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“A Facile α-Glucuronidation Using Methyl 1,2,3,4-Tetra-O-acetyl-D-glucuronate as Glycosyl Donor”
T. Du, K. Kaneko, Y. Sakai, M. Tsunoi, T. Yoshitake, A. Kotera, Y. Matsushima, T. Miura, T. Kajimoto,
Chem. Pharm. Bull. 70, 589-593, (2022).

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“Solvent-Triggered Long-Range Proton Transport in 7-Hydroxyquinoline Using a Sulfonamide Transporter Group”
K. Nakashima, A. Georgiev, D. Yordanov, Y. Matsushima, S. Hirashima, T. Miura, L. Antonov,
J. Org. Chem. 87, 6794-6806, (2022).

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“Asymmetric conjugate addition–cyclization of cyclohexane-1,2-dione with alkylidenemalononitriles using diaminomethylenemalononitrile organocatalyst”
Y. Matsushima, Y. Iino, Y. Tsuruta, K. Nakashima, S. Hirashima, T. Miura,
Tetrahedron Lett. 97,153773, (2022).

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“Organocatalytic one-pot asymmetric synthesis of 6-trifluoromethyl-substituted 7,8-dihydrochromen-6-ol”
K. Nakashima, A. Minai, Y. Okuaki, Y. Matsushima, S. Hirashima, T. Miura,
Tetrahedron Lett. 95,153733, (2022).

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“Asymmetric Direct Vinylogous Conjugate Addition of Substituted Furanone Derivatives to (E)- and (Z)-Benzoyl Acrylonitriles Using Organocatalysts”
D. Ishii, S. Hirashima, H. Akutsu, K. Nakashima, Y. Matsushima, T. Sakai, T. Miura,
Asian J. Org. Chem. e202200048, (2022).

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“Asymmetric Henry Reaction of Trifluoromethyl Enones with Nitromethane Using a N,N-Dibenzyl Diaminomethylenemalononitrile Organocatalyst”
M. Kawada, R. Tsuyusaki, K. Nakashima, M. Yamada, A. Kozakai, Y. Matsushima, S. Hirashima, T. Miura,
Chem. Asian J, 17, e202101299, (2022).

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“グリーンケミストリーを基盤とした有機分子触媒的不斉反応の開発”
平島 真一
Yakugaku zasshi, 141, 1137-1145, (2021).

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“Diaminomethylenemalononitrile as a Chiral Single Hydrogen Bond Catalyst: Application to Enantioselective Conjugate Addition of α-Branched Aldehydes”
M. Kawada, R. Tsuyusaki, K. Nakashima, H. Akutsu, S. Hirashima, T. Matsumoto, H. Yanai, T. Miura,
Chem. Asian J, 16, 2272-2275, (2021).

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“Acylhydrazone Subunits as a Proton Cargo Delivery System in 7-Hydroxyquinoline”
K. Nakashima, A. Petek, Y. Hori, A. Georgiev, S. Hirashima, Y. Matsushima, D. Yordanov, T. Miura, L. Antonov
Chem. Eur. J., 27, 11559-11566, (2021).

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“Asymmetric Direct Vinylogous Conjugate Addition of Substituted Furanone Derivatives to Benzoyl Acrylonitrile: Stereoselective Synthesis Toward Bicyclic γ-Lactams”
D. Ishii, S. Hirashima, K. Nakashima, H. Akutsu, T. Sakai, Y. Matsushima, M. Kawada, T. Miura,
Org. Lett., 23, 480-485, (2021).

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“Asymmetric Conjugate Addition of α-Cyanoketones to Benzoyl Acrylonitrile Derivatives Using a Diaminomethylenemalononitrile Organocatalyst”
H. Akutsu, K. Nakashima, Y. Kanetsuna, M. Kawada, S. Hirashima, T. Miura,
Synthesis, 52, 3874-3880, (2020).

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“Asymmetric Conjugate Addition of Phosphonates to Enones Using Cinchona–Diaminomethylenemalononitrile Organocatalysts”
R. Arai, S. Hirashima, T. Nakano, M. Kawada, H. Akutsu, K. Nakashima, T. Miura,
J. Org. Chem., 85, 8372-3878, (2020).

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“Organocatalytic asymmetric conjugate addition of substituted 5-benzylfurfurals to nitroalkenes based on stereocontrol of trienamine”
H. Akutsu, M. Ito, M. Kawada, K. Nakashima, S. Hirashima, T. Miura,
Tetrahedron Lett., 61, 151478, (2020).

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“Synthesis of Chiral γ,γ-Disubstituted γ-Butenolides via Direct Vinylogous Aldol Reaction of Substituted Furanone Derivatives with Aldehydes”
T. Sakai, S. Hirashima, Y. Matsushima, T. Nakano, D. Ishii, Y. Yamashita, K. Nakashima, Y. Koseki, T. Miura,
Org. Lett., 21, 2606-2609, (2019).

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“Highly efficient asymmetric conjugate addition of 5-benzylfurfurals to nitroalkenes using a thiourea organocatalyst”
H. Akutsu, K. Nakashima, S. Hirashima, H. Matsumoto, Y. Koseki, T. Miura,
Tetrahedron, 75, 2431-2435 , (2019).

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“Cinchona–Diaminomethylenemalononitrile Organocatalyst for the Highly Enantioselective Hydrophosphonylation of Ketones and Enones”
R. Arai, S. Hirashima, J. Kondo, K. Nakashima, Y. Koseki, T. Miura,
Org. Lett., 20, 5569-5572, (2018).

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“Stereoselective conjugate addition of ketones to alkylidene malonates using thiourea‐sulfonamide organocatalyst”
M. Kawada, K. Nakashima, S. Hirashima, T. Sakagami, Y. Koseki, T. Miura,
Chirality, 30, 1215-1224 (2018).

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“Asymmetric Conjugate Addition of α-Cyanoketones to Enones Using Diaminomethylenemalononitrile Organocatalyst”
K. Nakashima, Y. Noda, S. Hirashima, Y. Koseki, T. Miura,
J. Org. Chem., 83, 2402-2408 (2018).

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“Asymmetric conjugate addition of carbonyl compounds to nitroalkenes under solvent-free conditions using fluorous diaminomethylenemalononitrile organocatalyst”
S. Hirashima, T. Narushima, M. Kawada, K. Nakashima, K. Hanai, Y. Koseki, T. Miura,
Chem. Pharm. Bull., 65, 1185-1190 (2017).

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“Asymmetric conjugate addition of 5-benzylfurfurals to nitroalkenes using a diaminomethylenemalononitrile organocatalyst”
H. Akutsu, K. Nakashima, S. Hirashima, M. Kitahara, Y. Koseki, T. Miura,
Tetrahedron Lett., 58, 4759-4762 (2017).

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“Asymmetric Conjugate Addition of Nitroalkanes to Enones Using a Sulfonamide–Thiourea Organocatalyst”
M. Kawada, K. Nakashima, S. Hirashima, A. Yoshida, Y. Koseki, T. Miura,
J. Org. Chem., 82, 6986-6991 (2017).

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“Squaramide–Sulfonamide Organocatalyst for Asymmetric Direct Vinylogous Aldol Reactions”
T. Sakai, S. Hirashima, Y. Yamashita, R. Arai, K. Nakashima, A. Yoshida, Y. Koseki, T. Miura,
J. Org. Chem., 82, 4661-4667 (2017).

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“Design of Novel Hydrogen-Bonding Donor Organocatalysts and Their Application to Asymmetric Direct Aldol Reaction”
H. Akutsu, K. Nakashima, H. Yanai, A. Kotani, S. Hirashima, T. Yamamoto, R. Takahashi, A. Yoshida, Y. Koseki, H. Hakamata, T. Matsumoto, T. Miura,
Synlett, 28, 1363-1367 (2017).

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“Asymmetric chlorination of β-keto esters using diaminomethylenemalononitrile organocatalyst”
T. Sakai, S. Hirashima, K. Nakashima, C. Maeda, A. Yoshida, Y. Koseki, T. Miura,
Chem. Pharm. Bull., 64, 1781-1784 (2016).

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“Stereoselective conjugate addition of carbonyl compounds to maleimides using a diaminomethyleneindenedione organocatalyst”
K. Nakashima, M. Kawada, S. Hirashima, A. Kosugi, M. Kato, A. Yoshida, Y. Koseki, T. Miura,
Tetrahedron: Asymmetry, 27, 888-895 (2016).

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“Asymmetric Hydrophosphonylation of Aldehydes using a Cinchona-Diaminomethylenemalononitrile Organocatalyst”
S. Hirashima, R. Arai, K. Nakashima, N. Kawai, J. Kondo, Y. Koseki, T. Miura,
Adv. Synth. Catal., 357, 3863-3867 (2015).

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“Asymmetric conjugate addition of ketones to maleimide using diaminomethyleneindenedione organocatalyst”
K. Nakashima, M. Kawada, S. Hirashima, M. Kato, Y. Koseki, T. Miura, 
Synlett, 26, 1248-1252 (2015).

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“Pyrrolidine-Diaminomethylenemalononitrile Organocatalyst for Solvent-free Asymmetric Direct Aldol Reactions”
K. Nakashima, S. Hirashima, H. Akutsu, Y. Koseki, N. Tada, A. Itoh, T. Miura, 
Tetrahedron Lett., 56, 558-561 (2015).

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“Cinchona-Diaminomethylenemalononitrile Organocatalyst for Asymmetric Michael Addition of 1,3-Diketone to Nitroalkene”
S. Hirashima, K. Nakashima, Y. Fujino, R. Arai, T. Sakai, M. Kawada, Y. Koseki, N. Tada, A. Itoh, T. Miura,
Tetrahedron Lett., 55, 4619-4622 (2014).

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“Asymmetric Conjugate Addition of Malonate to a,b-Unsaturated Ketones in Water Using Sulfonamide Organocatalyst”
Y. Kamito, A. Masuda, H. Yuasa, N. Tada, A. Itoh, K. Nakashima, S. Hirashima, Y. Koseki, T. Miura,
Tetrahedron: Asymmetry, 25, 974-979 (2014).

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“Solvent-free asymmetric conjugate addition of malonates to enones using a diaminomethylenemalononitrile organocatalyst”
S. Hirashima, T. Sakai, K. Nakashima, N. Watanabe, Y. Koseki, K. Mukai, Y. Kanada, N. Tada, A. Itoh, T. Miura,
Tetrahedron Lett., 55, 4334-4337 (2014).

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“Pyrrolidine-diaminomethylenemalononitrile organocatalyst for Michael additions of carbonyl compounds to nitroalkenes under solvent-free conditions”
K. Nakashima, S. Hirashima, M. Kawada, Y. Koseki, N. Tada, A. Itoh, T. Miura,
Tetrahedron Lett., 55, 2703-2706 (2014).