Synthetic Studies of Liposidomycin : Studies of Stereochemistry and biological activity mechanism

• Project/Area Number: 16590008
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: Toyama Prefectural University
• Principal Investigator: NAKAJIMA Noriyuki Toyama Prefectural University, Faculty of Engineering, Department of Biochemistry, Professor, 工学部, 教授 (40188959)
• Project Period (FY): 2004 – 2006
• Project Status: Completed (Fiscal Year 2006)
• Budget Amount: ¥3,700,000 (Direct Cost: ¥3,700,000); Fiscal Year 2006: ¥500,000 (Direct Cost: ¥500,000); Fiscal Year 2005: ¥600,000 (Direct Cost: ¥600,000); Fiscal Year 2004: ¥2,600,000 (Direct Cost: ¥2,600,000)
• Keywords: nucleoside antibiotics / peptidoglycan / biosynthesis inhibitor / total synthesis / diazepanone ring / nitrobenzenesulfonamide protecting group / 構造活性相関

Research Abstract

Liposidomycins are a family of novel lipid-containing nucleoside antibiotics of unusual complexity, found in the culture filtrate and mycelia of streptomyces griseosporeus. They are selective antibiotics showing highly specific inhibition toward phospho-N-acetylmuramylpentapeptide transferase that is the primary stage of a lipid cycle in bacterial peptidoglycan synthesis. Liposidomycin B also inhibits in vitro formation of polyprenyl(pyro)phosphate N-acetylglucosamine, an intermediate in glycoconjugate biosynthesis. The structures were proposed on the basis of NMR and mass spectral evidence of degradation compound but the stereochemistry was revealed by X-ray crystallography analysis of caprazamycin that is an analog of liposidomycins.
We start to study the synthetic of liposidomycin degradation product. A stereocontrolled synthesis of the liposidomycin diazepanone ring system having a phenyl substituent has been achieved. In the presence of an amino group on the diazepanone ring, the introduction of a uracil group did failed. The N-glycosylation proceeded smoothly to obtain the uracil compound having electron-withdrawing nitrobenzenesulfonamide (Ns) and formyl protecting at an amino group on the diazepanone ring. The detailed examination of the N-glycosylation was accomplished for the total synthesis of liposidomycins.

Research Products

• [Journal Article] Synthetic Studies of Liposidomycin Degradation Product : Model Studies of Uracil Group Introduction (2007)
  • Author(s): Fukunishi, S., Ubukata, M., Nakajima, N.
  • Journal Title: Heterocycles 73(in press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Perianth Bottom-Specific Blue Color Development in Tulip cv. Murasakizuisho Requires Ferric Ions (2007)
  • Author(s): Shoji, K., Miki, N., Nakajima, N., Momonoi, K., Kato C., Yoshida, K.
  • Journal Title: Plant and Cell Physiology 48 Pages: 243-251
  • NAID: 10018519384
• [Journal Article] Epicatechin conjugated with fatty acid is a potent inhibitor of DNA polymerase and angiogenesis (2007)
  • Author(s): Matsubara, K., Saito, A., Tanaka, A., Nakajima, N., Akagi, R., Mori, M., Mizushina, Y.
  • Journal Title: Life Sciences 80 Pages: 1578-1585
• [Journal Article] Synthesis of galloyl-substituted procyanidin B4 series, and their DPPH radical scavenging activity and DNA polymerase inhibitory activity (2006)
  • Author(s): Sakuda, H., Saito, A., Mizushina, Y., Yoshida, H., Tanaka, A., Nakajima, N.
  • Journal Title: Heterocycles 67 Pages: 175-188
• [Journal Article] Catechin conjugated with fatty acid inhibits DNA polymerase and angiogenesis (2006)
  • Author(s): Matsubara, K, Saito A., Tanaka, A., Nakajima, N., Akagi, R., Mori, M., Mizushina, Y.
  • Journal Title: DNA ＆ Cell Biol. 25 Pages: 95-103
• [Journal Article] Synthesis of cyclic polygrycerols (2006)
  • Author(s): Kawagishi, T., Yoshikawa, K., Ubukata, M., Hamada, M., Nakajima, N.
  • Journal Title: Heterocycles 69 Pages: 107-111
• [Journal Article] Synthetic Studies of Liposidomycin Degradation Product : Attempt for Introduction of an Uracil group (2005)
  • Author(s): Fukunishi, S., Ubukata, M., Nakajima, N.
  • Journal Title: Heterocycles 66 Pages: 129-134
  • NAID: 40007080605
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Systematic Synthesis of Galloyl-substituted Procyanidin B 1 and B2, and Their Ability of DPPH Radical Scavenging Activity and Inhibitory Activity of DNA Polymerases (2005)
  • Author(s): Saito A., Mizushina, Y., Ikawa, H., Yoshida, H., Doi, Y., Tanaka, A., Nakajima, N.
  • Journal Title: Bioorg.Med.Chem. 13 Pages: 2759-2771
• [Journal Article] Structural Analysis of Catechin Derivatives, as Mammalian DNA Polymerase Inhibitors (2005)
  • Author(s): Saito A., Mizushina, Y., Ikawa, H., Yoshida, H., Doi, Y., Tanaka, A., Nakajima, N.
  • Journal Title: Biochem.Biophys.Res.Commun. 333 Pages: 101-109
• [Journal Article] Stereoselective Synthesis of Procyanidin Oligomers and Their Bioactivity (2005)
  • Author(s): Saito.A., Nakajima, N.
  • Journal Title: Journal of Synthetic Organic Chemistry, Japan 63 Pages: 982-994
  • NAID: 130000928676
• [Journal Article] Efficient stereoselective synthesis of proanthocyanidin trimers with TMSOTf-catalyzed intermolecular condensation (2004)
  • Author(s): A.Saito, A.Tanaka, M.Ubukata, N.Nakajima
  • Journal Title: Synlett Pages: 1069-1073
• [Journal Article] Stereoselection of 3,4-cis and 3,4-trans Catechin and Catechin Condensation under Intramolecular Coupling Method (2004)
  • Author(s): A.Saito, A.Tanaka, M.Ubukata, N.Nakajima
  • Journal Title: Synlett Pages: 2040-2042
• [Journal Article] Systematic synthesis of four epicatechin series procyanidin trimers andtheir in hibitory activity on the Maillard reaction and antioxidant activity (2004)
  • Author(s): A.Saito, Y.Doi, A.Tanaka, N.Matsuura, M.Ubukata, N.Nakajima
  • Journal Title: Bioorg.Med.Chem. 12 Pages: 4783-4790
• [Journal Article] Design and Synthesis of 16-Membered Hybrid Macrolide having a Thiazole side Chain on the Carbonolide Skeleton (2004)
  • Author(s): N.Nakajima, M.Ubukata
  • Journal Title: Heterocycles 64 Pages: 333-345
  • NAID: 40006603423
• [Journal Article] Systematic synthesis of galloyl-substituted procyanidin B1 and B2, and their ability of DPPH radical scavenging activity and inhibitory (2004)
  • Author(s): A.Saito, Y.Mizushina, H.Ikawa, H.Yosida, Y.Doi, A.Tanaka, N.Matsuura, N.Nakajima
  • Journal Title: Bioorg.Med.Chem. 13 Pages: 2759-2771
• [Journal Article] Synthetic Studies of Liposidomycin Degradation Product : Model Studies of Uracil Group Introduction
  • Author(s): Fukunishi, S., Ubukata, M., Nakajima, N.
  • Journal Title: Heterocycles 73 (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] Three Carbon-Heteroatom Bonds : Thio-, Seleno-, and Telluro-Carboxylic Acids and Derivatives ; Imidic Acids and Derivatives ; Ortho Acid Derivatives (2005)
  • Author(s): Nakajima, N., Ubukata, M.
  • Total Pages: 46
  • Publisher: Thieme Chemistry