Design and synthesis of non-proteinogenic amino acids and peptide foldamers by anodic functionalizaton

• Project/Area Number: 19790017
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Chemical pharmacy
• Research Institution: National Institute of Health Sciences (2008); Nagasaki University (2007)
• Principal Investigator: DEMIZU Yosuke National Institute of Health Sciences, 有機化学部, 研究官 (90389180)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,650,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥450,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2007: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: 非天然型アミノ酸 / ペプチド / 電極酸化 / フォールダマー / N-オキシル / 電極反応 / 酸化反応 / 環状アミン

Research Abstract

新たな構造特性と機能を併せ持つ新規な人工タンパク質の創製には、天然に存在しない人工アミノ酸を用いることが有用である。本研究では人工アミノ酸の効率的合成とその利用を目的とし研究遂行した。その結果、入手容易な天然アミノ酸から有機化学的手法と電気化学的手法を駆使したハイブリット手法により、人工アミノ酸の効率的合成に成功した。また、合成したアミノ酸とその誘導体は、酸化触媒として機能することを明らかとした。

Research Products

• [Journal Article] Convenient synthesis of enantiomerically enriched bicyclic proline and the corresponding N-oxyls (2008)
  • Author(s): Y. Demizu, H. Shiigi, H. Mori, K. Matsumoto, O. Onomura
  • Journal Title: Tetrahedron: Asymmetry 19 Pages: 2659-2665
  • Peer Reviewed
• [Journal Article] Effecient kinetic resolution of racemic-aminoaldehydes by oxidation with NIS (2008)
  • Author(s): D. Minato, Y. Nagasue, Y. Demizu, O. Onomura
  • Journal Title: Angew. Chem. Int. Ed 47 Pages: 9458-9461
  • Peer Reviewed
• [Journal Article] Oxidative C-C bond cleavage of N-alkoxycarbonylated cyclic amines by sodium nitrite in trifluoroacetic acid (2008)
  • Author(s): O. Onomura, A. Moriyama, K. Fukae, Y. Yamamoto, T. Maki, Y. Matsumura, Y. Demizu
  • Journal Title: Tetrahedron Lett 49 Pages: 6728-6731
  • NAID: 120006982372
  • Peer Reviewed
• [Journal Article] Regioselective protection of sugars catalyzed by dimethyltin dichloride (2008)
  • Author(s): Y. Demizu, Y. Kubo, H. Miyoshi, T. Maki, Y. Matsumura, N. Moriyama, O. Onomura
  • Journal Title: Org. Lett 10 Pages: 5075-5077
  • Peer Reviewed
• [Journal Article] Regioselective introduction of electrophiles into piperidine derivatives at the 4-position (2008)
  • Author(s): O. Onomura, N. Fujimura, T. Oda, Y. Matsumura, Y. Demizu
  • Journal Title: Heterocycles 76 Pages: 177-182
  • NAID: 120006984129
  • Peer Reviewed
• [Journal Article] Chiral azabicyclo-N-oxyls mediated enantioselective electrooxidation of sec-alcohols (2008)
  • Author(s): H. Shiigi, H.Mori, T. Tanaka, Y. Demizu, O. Onomura
  • Journal Title: Tetrahedron Lett 49 Pages: 5247-5251
  • NAID: 120006981658
  • Peer Reviewed
• [Journal Article] Diastereoselective arylation of L-proline derivatives at the 5-position (2008)
  • Author(s): O. Onomura, P. G. Kirira, T. Tanaka, S. Tsukada, Y. Matsumura, Y. Demizu
  • Journal Title: Tetrahedron 64 Pages: 7498-7503
  • NAID: 120006981712
  • Peer Reviewed
• [Journal Article] Asymmetric electrochemical oxidation of 1,2-diols, aminoalcohols and aminoaldehydes in the presenceof chiral copper catalyst (2008)
  • Author(s): D. Minato, H. Arimoto, Y. Nagasue, Y. Demizu, O. Onomura
  • Journal Title: Tetrahedron 64 Pages: 6675-6683
  • Peer Reviewed
• [Journal Article] High regioselective in electrochemical α-methoxylation of N-protected cyclic amines (2008)
  • Author(s): S. S. Libendi, Y. Demizu, Y. Matsumura, O. Onomura
  • Journal Title: Tetrahedron 64 Pages: 3935-3942
  • NAID: 120006981389
  • Peer Reviewed
• [Journal Article] Non-enzymatic kinetic resolution of 3-hydroxyalkanamides with chiral copper catalyst (2008)
  • Author(s): Y. Demizu, Y. Kubo, Y. Matsumura, O. Onomura
  • Journal Title: Synlett Pages: 433-437
  • NAID: 120006982422
  • Peer Reviewed
• [Journal Article] Efficient oxidation of alcohols electrochemically mediated by azabicyclo-N-oxyls (2008)
  • Author(s): Y. Demizu, H. Shiigi, T. Oda, Y. Matsumura, O. Onomura
  • Journal Title: Tetrahedron Lett 49 Pages: 48-52
  • NAID: 120006981360
  • Peer Reviewed
• [Journal Article] Computational study on secondary structure of oligopeptides containing α,α-disubstituted α-amino acids (2008)
  • Author(s): M. Kurihara, Y. Sato, F. Kaneko, H. Okuda, M. Nagano, Y. Demizu, M. Doi, M. Tanaka, H. Suemune
  • Journal Title: Peptide Science 2007 Pages: 137-138
  • NAID: 10021906747
  • Peer Reviewed
• [Journal Article] Efficient oxidation of alcohols electrochemically mediated by azabicyclo-N-oxyls (2008)
  • Author(s): Demizu, Y. et al.
  • Journal Title: Tetrahedron Letters 49 Pages: 48-52
  • NAID: 120006981360
  • Peer Reviewed
• [Journal Article] Non-enzymatic kinetic resolution of 3-hydroxyalkanamides with chiral copper catalyst (2008)
  • Author(s): Demizu, Y. et al.
  • Journal Title: Synlett Pages: 433-437
  • NAID: 120006982422
  • Peer Reviewed
• [Journal Article] High regioselective in electrochemical α-methoxylation of N-protected cyclic amines (2008)
  • Author(s): Samuel, S. S. et al.
  • Journal Title: Tetrahedron 64 Pages: 3935-3942
  • Peer Reviewed
• [Journal Article] Asymmetric electrochemical oxidation of 1,2-diols, aminoalcohols and aminoaldehydes in the presence of chiral copper catalyst (2008)
  • Author(s): Minato, D. et al.
  • Journal Title: Tetrahedron 64 Pages: 6675-6683
  • Peer Reviewed
• [Journal Article] Diastereoselective arylation of L-proline derivatives at the 5-position (2008)
  • Author(s): Onomura, O. et al.
  • Journal Title: Tetrahedron 64 Pages: 7498-7503
  • Peer Reviewed
• [Journal Article] Chiral azabicyclo-N-oxyls mediated enantioselective electrooxidation of sec-alcohols (2008)
  • Author(s): Shiigi, H. et al.
  • Journal Title: Tetrahedron Letters 49 Pages: 5247-5251
  • Peer Reviewed
• [Journal Article] Regioselective introduction of electrophiles into piperidine derivatives at the 4-position (2008)
  • Author(s): Onomura, O. et al.
  • Journal Title: Heterocycles 76 Pages: 177-182
  • Peer Reviewed
• [Journal Article] Regioselective protection of sugars catalyzed by dimethyltin dichloride (2008)
  • Author(s): Demizu, Y. et al.
  • Journal Title: Organic Letters 10 Pages: 5075-5077
  • Peer Reviewed
• [Journal Article] Oxidative C-C bond cleavage of N-alkoxycarbonylated cyclic amines by sodium nitrite in trifluoroacetic acid (2008)
  • Author(s): Onomura, O. et al.
  • Journal Title: Tetrahedron Letters 49 Pages: 6728-6731
  • Peer Reviewed
• [Journal Article] Effecient kinetic resolution of racemric-aminoaldehydes by oxidation with NIS (2008)
  • Author(s): Minato, D. et al.
  • Journal Title: Angew. Chem. Int. Ed. 47 Pages: 9458-9461
  • Peer Reviewed
• [Journal Article] Convenient synthesis of enantiomerically enriched bicyclic proline and the corresponding N-oxyls (2008)
  • Author(s): Demizu, Y. et al.
  • Journal Title: Tetrahedron : Asymmetry 19 Pages: 2659-2665
  • Peer Reviewed
• [Journal Article] Efficient oxidation of alcohols electrochemically mediated by azabicyclo-N-oxyls (2008)
  • Author(s): Demizu, Y., et. al.
  • Journal Title: Tetrahedron Letters 49 Pages: 48-52
  • NAID: 120006981360
  • Peer Reviewed
• [Journal Article] Non-enzymatic kinetic resolution of 3-hydroxyalkanamides with chiral copper catalyst (2008)
  • Author(s): Demizu, Y., et. al.
  • Journal Title: Synlett 3 Pages: 433-437
  • NAID: 120006982422
  • Peer Reviewed
• [Journal Article] Asymmetric tosylation of racemic 2-hydroxyalkanamides with chiral copper catalyst (2007)
  • Author(s): O. Onomura, M. Mitsuda, T. T. M. Nguyen, Y. Demizu
  • Journal Title: Tetrahedron Lett 48 Pages: 9080-9084
  • NAID: 120006981361
  • Peer Reviewed
• [Journal Article] Asymmetric oxidation of 1,2-diols using N-bromosuccinimide in the presence of chiral copper catalyst (2007)
  • Author(s): O. Onomura, H. Arimoto, Y. Matsumura, Y. Demizu
  • Journal Title: Tetrahedron Lett 48 Pages: 8668-8672
  • NAID: 120006981362
  • Peer Reviewed
• [Journal Article] Copper complex catalyzed asymmetric monosulfonylation of meso-vic-diols (2007)
  • Author(s): Y. Demizu, K. Matsumoto, O. Onomura, Y. Matsumura
  • Journal Title: Tetrahedron Lett 48 Pages: 7605-7609
  • NAID: 120006981364
  • Peer Reviewed
• [Journal Article] Lipase-catalyzed kinetic resolution of cyclic trans-1,2-diols bearing a diester moiety: Synthetic application to chiral seven-membered ring α,α-disubstituted α-amino acid (2007)
  • Author(s): M. Tanaka, Y. Demizu, M. Nagano, M. Hama, Y. Yoshida, M. Kurihara, H. Suemune
  • Journal Title: J. Org. Chem 72 Pages: 7750-7756
  • Peer Reviewed
• [Journal Article] Antiviral activity of 3-(3,5-dimethylbenzyl)uracil derivatives against HIV-1 and HCM (2007)
  • Author(s): T. Maruyama, Y. Demizu, S. Kozai, M. Witvrouw, C. Pannecouque, P. J. Balzarini, R. Snoecks, G. Andrei, E. De Clercq
  • Journal Title: Nucleosides, Nucleotides & Nucleic Acids 26 Pages: 1553-1558
  • Peer Reviewed
• [Journal Article] Controlling 310-helix and α-helix of short peptides in the solid state (2007)
  • Author(s): Y. Demizu, M. Tanaka, M. Nagano, M. Kurihara, M. Doi, T. Maruyama, H. Suemune
  • Journal Title: Chem. Pharm. Bull 55 Pages: 840-842
  • Peer Reviewed
• [Journal Article] 1,2-ジオール分子認識に基づく選択的分子変換反応 (2007)
  • Author(s): 松村功啓、尾野村治、出水庸介
  • Journal Title: 有機合成化学協会誌 第65巻 Pages: 46-55
  • NAID: 10018578272
  • Peer Reviewed
• [Journal Article] Computational study on conformation of oligopeptides containing chiral cyclic α,α-disubstituted a-amino acids (2007)
  • Author(s): M. Kurihara, Y. Sato, W. Hakamata, H. Okuda, Y. Demizu, M. Nagano, N. Kawabe, M. Doi, M. Tanaka, H. Suemune
  • Journal Title: Peptides 2006 Pages: 546-547
  • Peer Reviewed
• [Journal Article] Side-chain chiral centers of amino acids and helical-screw handedness of their peptides (2007)
  • Author(s): M. Tanaka, M. Nagano, Y. Demizu, K. Anan, M. Kurihara, M. Doi, H. Suemune
  • Journal Title: Peptides 2006 Pages: 268-269
  • Peer Reviewed
• [Journal Article] Secondary structure of heteropeptides using chiral cyclic α,α-disubstituted amino acids (2007)
  • Author(s): M. Nagano, M. Tanaka, Y. Demizu, M. Kurihara, M. Doi, H. Suemune
  • Journal Title: Peptides 2006 Pages: 476-477
  • Peer Reviewed
• [Journal Article] Asymmetric tosylation of racemic 2-hydroxyalkanamides with chiral copper catalyst (2007)
  • Author(s): Onomura, O., et. al.
  • Journal Title: Tetrahedron Letters 48 Pages: 9080-9084
  • Peer Reviewed
• [Presentation] Chiral azabicyclo-N-oxyls and asymmetric oxidation of secondary alcohols mediated by them (2008)
  • Author(s): Demizu, Y.; Shiigi, H.; Mori, H.; Matsumoto, K.; Matsumura, Y.; Onomura, O
  • Organizer: 213th ECS Meeting
  • Place of Presentation: Phoenix
• [Presentation] 分子認識に基づくアルコール類の不斉トシル化 (2008)
  • Author(s): 出水庸介, ,満田勝, 松本和也, 松村功啓, 尾野村治
  • Organizer: 日本薬学会第128年会
• [Presentation] Chiral azabicyclo-N-oxyls and asymmetric oxidation of secondary alcohols mediated by them (2008)
  • Author(s): Demizu, Y. et al.
  • Organizer: The 213th ECS Meeting
  • Place of Presentation: Phoenix, USA
• [Presentation] 新規キラルN-オキシルを用いる二級アルコールの不斉電極酸化 (2007)
  • Author(s): 出水庸介
  • Organizer: 第31回有機電子移動化学討論会
  • Place of Presentation: 鳥取
  • Year and Date: 2007-06-14
• [Presentation] Electrochemical oxidation of alcohols catalyzed by new organic mediators (2007)
  • Author(s): Demizu, Y.
  • Organizer: 211th ECS Meeting
  • Place of Presentation: アメリカ
  • Year and Date: 2007-05-11
• [Presentation] 分子認識に基づくアルコール類の不斉トシル化 (2007)
  • Author(s): 出水庸介
  • Organizer: 日本薬学会第128年会
  • Place of Presentation: 横浜
  • Year and Date: 2007-03-26
• [Presentation] 分子認識に基づくキラル銅触媒を用いたアルコール類の不斉トシル化 (2007)
  • Author(s): 出水庸介
  • Organizer: 第1回若手交流合宿セミナー
  • Place of Presentation: 福岡
• [Presentation] 新規キラルN-オキシンを用いる二級アルコールの不斉電極酸化 (2007)
  • Author(s): 出水庸介, 末続肇, 尾野村治, 松村功啓
  • Organizer: 第31回有機電子移動化学討論会
  • Place of Presentation: 鳥取
• [Presentation] Electrochemical oxidation of alcohols catalyzed by new organic mediators (2007)
  • Author(s): Demizu, Y.; Oda, T.; Onomura, O.; Matsumura, Y
  • Organizer: 211th ECS Meeting
  • Place of Presentation: Chicago
• [Remarks]
  • URL: http://www.nihs.go.jp/doc/2shitu.html
• [Patent(Industrial Property Rights)] 光学活性α-アシルオキシリン酸誘導体の製造方法 (2008)
  • Inventor(s): 尾野村冶, 出水庸介, 森山敦, 岩崎史哲
  • Industrial Property Rights Holder: 尾野村冶, 出水庸介, 森山敦, 岩崎史哲
  • Industrial Property Number: 2008-286370
  • Filing Date: 2008-11-07
• [Patent(Industrial Property Rights)] ラムノシドエステル誘導体およびその製造方法 (2008)
  • Inventor(s): 尾野村冶, 出水庸介, 久保裕紀, 岩崎史哲
  • Industrial Property Rights Holder: 尾野村冶, 出水庸介, 久保裕紀, 岩崎史哲
  • Industrial Property Number: 2008-192243
  • Filing Date: 2008-07-25
• [Patent(Industrial Property Rights)] キシロシドエステル誘導体およびその製造方法 (2008)
  • Inventor(s): 尾野村冶, 出水庸介, 岩崎史哲
  • Industrial Property Rights Holder: 尾野村冶, 出水庸介, 岩崎史哲
  • Industrial Property Number: 2008-075320
  • Filing Date: 2008-03-24
• [Patent(Industrial Property Rights)] 光学活性アミノ酸エステル誘導体、及び光学活性アミノアセタール誘導体の製造方法 (2008)
  • Inventor(s): 尾野村冶, 出水庸介, 山本博将
  • Industrial Property Rights Holder: 尾野村冶, 出水庸介, 山本博将
  • Industrial Property Number: 2008-072911
  • Filing Date: 2008-03-21
• [Patent(Industrial Property Rights)] グルコシドエステル誘導体およびその製造方法 (2008)
  • Inventor(s): 尾野村冶, 出水庸介, 岩崎史哲
  • Industrial Property Rights Holder: 尾野村冶, 出水庸介, 岩崎史哲
  • Industrial Property Number: 2008-068124
  • Filing Date: 2008-03-17
• [Patent(Industrial Property Rights)] ピラノシドジエステル化合物及びその製造方法 (2008)
  • Inventor(s): 尾野村冶, 出水庸介, 岩崎史哲
  • Industrial Property Rights Holder: 尾野村冶, 出水庸介, 岩崎史哲
  • Industrial Property Number: 2008-057503
  • Filing Date: 2008-03-07
• [Patent(Industrial Property Rights)] 含窒素レドックス触媒 (2008)
  • Inventor(s): 松村功啓, 尾野村冶, 出水庸介
  • Industrial Property Rights Holder: 松村功啓, 尾野村冶, 出水庸介
  • Filing Date: 2008-03-28
• [Patent(Industrial Property Rights)] 脂肪族ジカルボン酸化合物の製造方法 (2008)
  • Inventor(s): 尾野村冶, 出水庸介, 岩崎史哲
  • Industrial Property Rights Holder: 尾野村冶, 出水庸介, 岩崎史哲
  • Industrial Property Number: 2008-025594
  • Filing Date: 2008-02-05
• [Patent(Industrial Property Rights)] 光学活性モノスルホネート化合物の製造方法 (2008)
  • Inventor(s): 松村功啓, 尾野村冶, 出水庸介
  • Industrial Property Rights Holder: 松村功啓, 尾野村冶, 出水庸介
  • Patent Publication Number: 2008-290981
  • Acquisition Date: 2008-12-04
• [Patent(Industrial Property Rights)] α、α-ジ置換環状含窒素化合物の製造方法 (2008)
  • Inventor(s): 松村功啓, 尾野村冶, 出水庸介
  • Industrial Property Rights Holder: 松村功啓, 尾野村冶, 出水庸介
  • Patent Publication Number: 2008-240106
  • Acquisition Date: 2008-10-09
• [Patent(Industrial Property Rights)] 光学活性ビスオキサゾリン-銅錯体を不斉触媒おするN-保護アミノアルコール化合物の不斉エステル化反応 (2008)
  • Inventor(s): 松村功啓, 尾野村冶, 出水庸介
  • Industrial Property Rights Holder: 松村功啓, 尾野村冶, 出水庸介
  • Patent Publication Number: 2008-037865
  • Acquisition Date: 2008-02-21
• [Patent(Industrial Property Rights)] 脂肪族ジカルボン酸化合物の製造方法 (2008)
  • Inventor(s): 尾野村治, 出水庸介, 岩崎史哲
  • Industrial Property Rights Holder: 尾野村治, 出水庸介, 岩崎史哲
  • Industrial Property Number: 2008-025594
  • Filing Date: 2008-02-05
• [Patent(Industrial Property Rights)] 含窒素レドックス触媒 (2008)
  • Inventor(s): 松村功啓, 尾野村治, 出水庸介
  • Industrial Property Rights Holder: 松村功啓, 尾野村治, 出水庸介
  • Filing Date: 2008-03-28
  • Overseas
• [Patent(Industrial Property Rights)] ピラノシドジエステル化合物及びその製造方法 (2008)
  • Inventor(s): 尾野村治, 出水庸介, 岩崎史哲
  • Industrial Property Rights Holder: 尾野村治, 出水庸介, 岩崎史哲
  • Industrial Property Number: 2008-057503
  • Filing Date: 2008-03-07
• [Patent(Industrial Property Rights)] グルコシドエステル誘導体およびその製造方法 (2008)
  • Inventor(s): 尾野村治, 出水庸介, 岩崎史哲
  • Industrial Property Rights Holder: 尾野村治, 出水庸介, 岩崎史哲
  • Industrial Property Number: 2008-068124
  • Filing Date: 2008-03-17
• [Patent(Industrial Property Rights)] 光学活性アミノ酸エステル誘導体、及び光学活性アミノアセタール誘導体の製造方法 (2008)
  • Inventor(s): 尾野村治, 出水庸介, 山本博将
  • Industrial Property Rights Holder: 尾野村治, 出水庸介, 山本博将
  • Industrial Property Number: 2008-072911
  • Filing Date: 2008-03-21
• [Patent(Industrial Property Rights)] キシロシドエステル誘導体およびその製造方法 (2008)
  • Inventor(s): 尾野村治, 出水庸介, 岩崎史哲
  • Industrial Property Rights Holder: 尾野村治, 出水庸介, 岩崎史哲
  • Industrial Property Number: 2008-075320
  • Filing Date: 2008-03-24
• [Patent(Industrial Property Rights)] ラムノシドエステル誘導体およびその製造方法 (2008)
  • Inventor(s): 尾野村治, 出水庸介, 久保裕紀, 岩崎史哲
  • Industrial Property Rights Holder: 尾野村治, 出水庸介, 久保裕紀, 岩崎史哲
  • Industrial Property Number: 2008-192243
  • Filing Date: 2008-07-25
• [Patent(Industrial Property Rights)] 光学活性α-アシルオキシリン酸誘導体の製造方法 (2008)
  • Inventor(s): 尾野村治, 出水庸介, 森山敦, 岩崎史哲
  • Industrial Property Rights Holder: 尾野村治, 出水庸介, 森山敦, 岩崎史哲
  • Industrial Property Number: 2008-286370
  • Filing Date: 2008-11-07
• [Patent(Industrial Property Rights)] 光学活性モノスルホネート化合物の製造方法 (2008)
  • Inventor(s): 松村功啓, 尾野村治, 出水庸介
  • Industrial Property Rights Holder: 松村功啓, 尾野村治, 出水庸介
  • Patent Publication Number: 2008-290981
  • Acquisition Date: 2008-12-04
• [Patent(Industrial Property Rights)] α, α-ジ置換環状含窒素化合物の製造方法 (2008)
  • Inventor(s): 松村功啓, 尾野村治, 出水庸介
  • Industrial Property Rights Holder: 松村功啓, 尾野村治, 出水庸介
  • Patent Publication Number: 2008-240106
  • Acquisition Date: 2008-10-09
• [Patent(Industrial Property Rights)] 光学活性ビスオキサゾリン-銅錯体を不斉触媒とするN-保護アミノアルコール化合物の不斉エステル化反応 (2008)
  • Inventor(s): 松村功啓, 尾野村治, 出水庸介
  • Industrial Property Rights Holder: 松村功啓, 尾野村治, 出水庸介
  • Patent Publication Number: 2008-037865
  • Acquisition Date: 2008-02-21
• [Patent(Industrial Property Rights)] 光学活性α-スルホニルオキシカルボン酸アミド誘導体及びそれらの製造方法 (2007)
  • Inventor(s): 尾野村冶, 出水庸介, 岩崎史哲
  • Industrial Property Rights Holder: 尾野村冶, 出水庸介, 岩崎史哲
  • Industrial Property Number: 2007-265700
  • Filing Date: 2007-10-11
• [Patent(Industrial Property Rights)] 光学活性α-スルホニルオキシカルボン酸アミド誘導体及びそれらの製造方法 (2007)
  • Inventor(s): 尾野村治、出水庸介、岩崎史哲
  • Industrial Property Rights Holder: 尾野村治、出水庸介、岩崎史哲
  • Industrial Property Number: 2007-265700
  • Filing Date: 2007-10-11