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Bioorganic Studies on the Mechanisms of Biologically Active Compounds

生物活性化合物机制的生物有机研究

基本信息

批准号：
09660115
负责人：
ICHIKAWA Yoshiyasu
金额：
$ 1.79万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09660115/
关键词：
tautomycin protein phosphatase inhibitor amino sugars D-perosamine antigenic LPS antibiotic methyl-beta-D-vicenisaminide

项目摘要

1) Improved method for the esterification of each segment in the synthesis of tautomycin have been developed. Use of the diol segment B/C have bee achieved in better and more efficient manner. This method pave the way to the synthesis of the tautomycin derivatives for the search of the mechanism and action of protein phosphatase-inhibitor interactions.2) The synthesis of tautomycin-okadaic acid hybrid molecule have been explored with the search of the mechanism and action of protein phosphatase-inhibitor interactions in mind. Coupling reaction of segment C of okadaic acid with segment B of tautomycin followed by the efficient esterification developed above provided the tautomycin-okadaic acid hybrid molecule. Inhibition assay of the tautomycin-okadaic acid hybrid molecule revealed that the hybrid molecule inhibits PP2A more effectively than PP1. This result strongly suggested that design of inhibitor specific to each protein phosphatase is possible by using molecular recognition.3) A n … More ew approach for the synthesis of amino sugars using an allyl cyanate-to-isocyanate rearrangement has been developed. The key feature in this method involves introduction of the nitrogen substituents into the pyranose framework by [3,3] sigmatropic rearrangement of an allyl cyanate. Subsequent functionalization of the allyl amine moiety by either hydroxylation or cyclofunctionalization completed the synthesis of two amino sugars, D-perosamine and D-vicenisamine. 4-Amino-4,6-dideoxy-D-mannose (D-perosamine) was first discovered in a polyene macrolide antibiotic perimycin and was later recognized the presence in the lipopolysaccharide (LPS) of Vivrio cholera 569B (Inaba). Further investigation revealed that N-formylated-D-perosamine was a component of a repeating pentasaccharide unit in O-chains of the LPS of Yersinia enterocolitica and Brucella abortus. These findings established a molecular basis for extensive serological cross-reactivity between the antigenic LPS.Structual studies of vicenistatin isolated from Streptomyces sp. HG 34 as a new antitumor antibiotic revealed that vicenistatin contains an amino sugar vicenisamine. Degradation study by Shindo et al. showed that methanolysis of vicenistatin yielded the methyl-beta-D-vicenisaminide. Less

1)改进了牛磺酸霉素合成中各段的酯化反应方法。以更好和更有效的方式实现了二醇B/C段的使用。该方法为进一步研究蛋白质磷酸酶-抑制剂相互作用的机理和作用奠定了基础。2)从蛋白质磷酸酶-抑制剂相互作用的机理和作用出发，探索了交托霉素-冈田酸杂化分子的合成。将冈田酸的C段与他托霉素的B段偶联，然后进行高效的酯化反应，制得了冈田酸杂化分子。对交托霉素-冈田酸杂化分子的抑制实验表明，杂化分子比PP1更有效地抑制PP2A。这一结果有力地表明，利用分子识别技术设计针对每种蛋白磷酸酶的抑制剂是可能的。3)A n…利用氰酸烯丙酯到异氰酸酯的重排反应合成氨基糖的新方法已经被开发出来。该方法的主要特点是通过氰酸烯丙酯的[3，3]顺式重排将氮取代基引入吡喃糖骨架。随后通过羟化或环官能化对烯丙基胺部分进行官能化，合成了两种氨基糖：D-香草胺和D-香草胺。4-氨基-4，6-二脱氧-D-甘露糖(D-perosamine)最先在多烯大环内酯类抗生素perycin中被发现，后来被证实存在于霍乱弧菌569B(Inaba)的脂多糖(LPS)中。进一步的研究表明，N-甲酰化-D-珀罗胺是小肠结肠炎耶尔森菌和流产布鲁氏菌脂多糖O链中重复的五糖单元的一部分。这些发现为抗原性LPS之间广泛的血清学交叉反应奠定了分子基础。从链霉菌中分离出的Vienistatin的结构研究。HG-34作为一种新的抗肿瘤抗生素，发现其含有一种氨基糖--维克西胺。Shindo等人的降解研究。结果表明，维菌素的甲基化反应生成了甲基-β-D-维菌胺。较少