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）改善了金霉素合成器的方法，这是更好，更有效的方式。在搜索蛋白质磷酸酶相互作用的机理和作用时，bave bave bave bave bave。分子的混合分子比PP1更有效地抑制PP2A。已经开发了异氰酸酯重排。 D-VICEN ISAMINE。甲基化D-D-可---菌糖是耶尔森氏菌的O-chains中的重复糖单元的组成部分Shindo等人的Radation Studo表明，Vicenistatin的金属分析产生了甲基-Beta-D-维烯胺。