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1992 Fiscal Year Final Research Report Summary

Studies on the Structure-activity Relationship and on Synthesis of the Antibiotic Nosiheptide

Research Project

Project/Area Number 03640477
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 天然物有機化学
Research InstitutionIWAKI MEISEI UNIVERSITY

Principal Investigator

YOSHIMURA Juji  IWAKI MEISEI UNIV., Science and Engineering, Professor, 理工学部, 教授 (20016017)

Co-Investigator(Kenkyū-buntansha) UMEMURA Kazuyuki  IWAKI MEISEI UNIV., Science and Engineering, Assistant professor, 理工学部, 助手 (90221811)
Project Period (FY) 1991 – 1992
KeywordsNosiheptide / Structure-activity relationship / Peptide antibiotic / Fragment E / Fragment D / Karnamicin
Research Abstract

i) Studies on the structure-activity relationship
A bicyclic polypeptide antibiotic, Nosiheptide is active against Gram-positive bacteria. Its mode of action on bacterial protein synthesis is known to inhibit functions of elongation factors Tu and to G and reduce greatly the synthesis of guanosine penta- and tetraphosphates in response to stringent factor, however, detailed conformational relationship is still unknown. To clarify this relationship, we have examined activities of several partially decomposed products. The activities of these products were generally decreased, and the effect of the elimination of the indole moiety (Fragment E) was grater than that of dehydroalanine moiety. Among the oxidation products, the effect of the oxidation of two aliphatic secondary hydroxyl groups with dimethylsulfoxide was unexpectedly much greater than that of the cleavage of one peptide ring with osmium tetroxide or lead tetraacetate, indicating the hydroxyl groups might be the recognition site … More . Further detailed examinations will be desirable.
ii) Synthetic studies
Fragment E, 3-methyl-4-hydroxyindole 2-carboxylic acid, of Nosiheptide was easily synthesized from 2-methyl-3-nitrobenzyl alcohol by Reissert method. For the synthesis of Fragment D, new routs from optically active 1, 2, 4-butanetriol or L-pyroglutamic acid were developed. Fragment C, 2-(1'-amino-1'propenyl) thiazole 4-carboxylic acid, and its peptides were synthesized by the thioamide method, including the condensation of an amino acid and N-carboxy-alpha-dehydroaminobutylic acid anhydride. As a previous research for the synthesis of remaining Fragment A, total synthesis of karnamicin which includes rather simple Fragment A structure was carried out. Its thiazole 4-carboxylic acid part was constructed from levulinic acid, and the synthesis of 3-hydroxypyridine is still undergoing. After synthesizing Fragment A, these fragments shall be used for the total synthesis of Nosiheptide, and the results mentioned above have been and shall be presented elsewhere. Less

  • Research Products

    (2 results)

All Other

All Publications (2 results)

  • [Publications] Yutaka NAKAMURA: "Convenient Synthesis of Thiazoles Incorporated with α-Dehydroamino Acid and Dehydropeptide Structures" CHEMISTRY LETTERS. 1005-1008 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.NAKAMURA, C.SHIN, K.UMEMURA, and J.YOSHIMURA: "Convenient Synthesis of Thiazoles Incorporated with alpha-Dehydroamino Acid and Dehydropeptide Structures" CHEMISTRY LETTERS. 1005-1008 (1992)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1994-03-24  

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