Solid Phase Synthesis in Water-Development of Green Chemistry

• Project/Area Number: 14572024
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: Kobe Gakuin University
• Principal Investigator: KAWASAKI Koichi Kobe Gakuin University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (40068242)
• Co-Investigator(Kenkyū-buntansha): MAEDA Mitsuko Kobe Gakuin University, Faculty of Pharmaceutical Sciences, Senior Assistant, 薬学部, 助手 (90131531) ; HOJO Keiko Kobe Gakuin University, Faculty of Pharmaceutical Sciences, Research Assistant, 薬学部, 実験助手 (20289028)
• Project Period (FY): 2002 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥3,200,000 (Direct Cost: ¥3,200,000); Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000); Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000); Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
• Keywords: solid phase synthesis / peptide synthesis / green chemistry / Leu-enkephalin / water-soluble protecting group / water / 水中合成 / 2-(4-sulfophenyl)ethoxycarbonyl group / 水中固相合成 / エンケファリン / 水溶性保護アミノ酸 / 水系固相法合成 / 2-[phenyl(methyl)sulfonio]eyhoxycarbonyl基

Research Abstract

Solid phase peptide synthesis (SPPS) is a well-established technique for the facile and rapid preparation of peptides, but it requires large amounts of organic solvents. Since the safe disposal of organic solvents is an important environmental issue, the ability to synthesize peptides in an aqueous medium would be preferable. In order to do so, water-soluble N-protected amino acids are necessary. We have successfully used the water-soluble N-protecting groups, 2-[phenyl(methyl)sulfonio]ethoxycarbonyl (Pms), ethanesulfonylethoxycarbonyl (Esc) and 2-(4-sulfophenylsulfonyl)ethoxycarbonyl (Sps), for the SPPS of Leu-enkephalin amide in water.

Research Products

• [Journal Article] Design of reagents for preparing water-soluble N-protected amino acids. (2005)
  • Author(s): Hojo, K., Maeda, M., Kawasaki, K.
  • Journal Title: Innovation and Perspectives in Solid Phase Synthesis & Combinatorial Libraries 2004 (Edited by Epton, R.)(Mayflower Wordwide Limited, London, England, UK) Pages: 233-236
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Application of ethanesulfonylethoxycarbonyl (Esc) group for solid phase synthesis in water. (2005)
  • Author(s): Hojo, K., Kita, E., Yamamoto, S., Yamaguchi, F., Maeda, M., Kawasaki, K.
  • Journal Title: Innovation and Perspectives in Solid Phase Synthesis & Combinatorial Libraries 2004 (Edited by Epton, R.)(Mayflower Wordwide Limited, London, England, UK) Pages: 237-240
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Solid-phase peptide synthesis in water. part 3 : a water-soluble N-protecting group, 2-[pheny(methyl)sulfonio]ethoxycarbonyl tetrafluoroborate, and its application to solid phase peptide synthesis in water. (2004)
  • Author(s): Hoji, K., Maeda, M., Kawasaki, K.
  • Journal Title: Tetrahedron 60 Pages: 1875-1886
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Peptide synthesis in water IV. preparation of N-ethanesulfonylethoxy-carbonyl(Esc) amino acids and their application to solid phase peptide synthesis (2004)
  • Author(s): Hojo, K., Maeda, M., Smith, T.J., Kita, E., Yamaguchi, F., Yamamoto, F., Kawasaki, K.
  • Journal Title: Chem.Pharm.Bull. 52 Pages: 422-427
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 2-(4-Sulfophenylsulfonyl)ethoxycarbonyl group : a new water-soluble N-protecting group and ots application to solid phase peptide synthesis in water. (2004)
  • Author(s): Hojo, K., Maeda, M., Kawasaki, K.
  • Journal Title: Tetrahedron Lettters 45 Pages: 9293-9295
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Design of reagents for preparing water-soluble N-protected amino acids. (2004)
  • Author(s): Hojo, K., Maeda, M., Kawasaki, K.
  • Journal Title: Innovation and Perspectives in Solid Phase Synthesis & Combinatorial Libraries 2004 Pages: 233-236
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Solid-phase peptide synthesis in water. part 3 : a water-soluble N-protecting group, 2-[pheny(methyl)sulfonio]ethoxycarbonyl tetrafluoroborate, and its application to solid phase peptide synthesis in water. (2004)
  • Author(s): Hojo, K., Maeda, M., Kawasaki, K.
  • Journal Title: Tetrahedron 60 Pages: 1875-1886
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Peptide synthesis in water IV. preparation of N-ethanesulfonylethoxy- carbonyl (Esc) amino acids and their application to solid phase peptide synthesis (2004)
  • Author(s): Hojo, K., Maeda, M., Smith T.J., Kita, E., Yamaguchi, F., Yamamoto, F., Kawasaki, K.
  • Journal Title: Chem.Pharm.Bull. 52 Pages: 422-427
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] 2-(4-Sulfophenylsulfonyl)ethoxycarbonyl group : a new water-soluble N-protecting group and ots application to solid phase peptide synthesis in water. (2004)
  • Author(s): Hojo, K., Maeda, M., Kawasaki, K.
  • Journal Title: Tetrahedron Lett 45 Pages: 9293-9295
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Solid phase synthesis in water : application of the ethansulfonylethoxycarbonyl (Esc) group. (2004)
  • Author(s): Hojo, K., Kita, E., Yamamoto, S., Yamaguchi, F., Maeda, M., Kawasaki, K.
  • Journal Title: Peptide Science 2003 (Edited by Ueki, M.)(PROTEIN RESEARCH FOUNDATION, Minoh-shi, Japan) Pages: 145-146
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Solid-phase synthesis in water. Part 3 : A water-soluble N-protecting group, 2-[phenyl(methyl)sulfonio]ethoxycarbonyl tetrafluoroborate, and its application to solid phase peptide synthesis in water (2004)
  • Author(s): Keiko Hojo, Mitsuko Maeda, Koichi Kawasaki
  • Journal Title: Tetrahedron 60 Pages: 1875-1886
• [Journal Article] 2-(4-sulfophenyl)ethoxycarbonyl group : a new water-soluble N-protecting group and its application to solid phase peptide synthesis in water (2004)
  • Author(s): Keiko Hojo, Mitsuko Maeda, Koichi Kawasaki
  • Journal Title: Tetrahedron Letters 45 Pages: 9293-9295
• [Journal Article] A New Reagent, 2-[Phenyl(methyl)sulfonio]ethyl-4-nitro- phenylcarbonate Tetrafluoroborate (Pms-ONp), for Preparing Water-Soluble N-Protected Amino Acids (2003)
  • Author(s): Hojo, K., Maeda, M., Takahara, Y, Yamamoto, S., Kawasaki, K.
  • Journal Title: Tetrahedron Lett. 44 Pages: 2849-2851
  • NAID: 80015974544
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A Water Soluble N-Protecting Group, 2-[Phenyl(methyl)-sulphonio]ethyloxycarbonyl Tetrafluoroborate and Its Application to Solid Phase Peptide Synthesis in Water. (2003)
  • Author(s): Hojo, K., Maeda, M., Kawasaki, K.
  • Journal Title: Innovation and Perspectives in Solid Phase Synthesis & Combinatrial Libraries 2002 (Edited by Epton, R.)(Mayflower Wordwide Limited, Kingswinford, England) Pages: 211-212
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A New Reagent, 2-[Phenyl(methyl)sulfonio]ethyl-4-nitro-phenylcarbonate Tetrafluoroborate (Pms-ONp), for Prepareing Water-Soluble N-Protected Amino Acids. (2003)
  • Author(s): Hojo, K., Maeda, M., Kawasaki, K.
  • Journal Title: Peptide Science 2002 (Edited by Yamada, T.)(PROTEIN RESEARCH FOUNDATION, Minoh-shi, Japan) Pages: 153-154
  • NAID: 80015974544
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A New Reagent, 2-[Phenyl(methyl)sulfonio]ethyl-4-nitro-phenylcarbonate Tetrafluoroborate(Pms-ONp), for Preparing Water-Soluble N-Protected Amino Acids (2002)
  • Author(s): Hojo, K., Maeda, M., Takahara, Y., Yamamoto, S., Kawasaki, K.
  • Journal Title: Tetrahedron Letters 44 Pages: 2849-2852
  • NAID: 80015974544
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A Water Soluble N-Protecting Group, 2-[Phenyl(methyl)-sulphonio]ethyloxycarbonyl Tetrafluoroborate and Its Application to Solid Phase Peptide Synthesis in Water. (2002)
  • Author(s): Hojo, K., Maeda, M., Kawasaki, K.
  • Journal Title: Peptide Science 2001 (Edited by Aoyagi, H.)(PROTEIN RESEARCH FOUNDATION, Minoh-shi, Japan) Pages: 41-42
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Keiko Hojo, Mitsuko Maeda, Koichi Kawasaki: "Solid phase peptide synthesis in water. III. A water-soluble N-protecting group, 2-[phenyl(methyl)sulfonio]ethoxycarbonyl tetrafluoroborate, and its application to solid phase peptide synthesis"Tetrahedron. 60. 1875-1886 (2004)
• [Publications] Keiko Hojo, Mitsuko Maeda, Timothy J.Smith, Eriko Kita, Fumie Yamaguchi, Sachiko Yamamoto, Koichi Kawasaki: "Peptide synthesis in water IV. Preparation of N-ethanesulfonylethoxy-Carbonyl (Esc) amino acids and their application to solid phase peptide synthesis"Chem.Pharm.Bull.. 27・4(In press). (2004)
• [Publications] 北條恵子, 前田光子, 川崎紘一: "A New Reagent, 2-[Phenyl(methyl)sulfonio]ethyl-4-nitrophenylcarbonate Tetrafluoroborate(Pms-ONp), for Preparing Water-soluble N-Protected amino acids"Tetrahedron Letters. 44. 2849-2851 (2003)