Bioorganic Studies on the Mechanisms of Biologically Active Compounds

1)对互变霉素合成中各链段的酯化方法进行了改进。已经以更好和更有效的方式实现了二醇链段B/C的使用。该方法为研究蛋白磷酸酶抑制剂与互变霉素的相互作用机理和作用奠定了基础。2）以蛋白磷酸酶抑制剂与互变霉素的相互作用机理和作用为出发点，对互变霉素-冈田酸杂合分子的合成进行了探索。冈田酸的片段C与互变霉素的片段B的偶联反应，随后是上述开发的有效酯化，提供了互变霉素-冈田酸杂合分子。互变霉素-冈田酸杂合分子的抑制测定揭示杂合分子比PP 1更有效地抑制PP 2A。这一结果有力地表明，利用分子生物学技术设计针对每种蛋白磷酸酶的抑制剂是可能的。 ...更多信息 已经开发了使用氰酸烯丙酯到异氰酸酯重排来合成氨基糖的新方法。该方法的主要特点是通过氰酸烯丙酯的[3，3] σ转移重排将氮取代基引入到吡喃糖骨架中。随后通过羟基化或环官能化的烯丙基胺部分的官能化完成了两种氨基糖，D-perosamine和D-vicenisamine的合成。4-氨基-4，6-二脱氧-D-甘露糖（D-perosamine）首先在多烯大环内酯抗生素perimycin中发现，后来在Vivrio cholera 569 B（Inaba）的脂多糖（LPS）中发现。进一步的研究表明，N-甲酰化-D-perosamine是小肠结肠炎耶尔森氏菌和流产布鲁氏菌的LPS的O-链中的重复五糖单元的组分。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HG 34中分离的维西他汀作为一种新型抗肿瘤抗生素的结构研究表明，维西他汀含有一个氨基糖维西胺。Shindo et al.的降解研究表明，维西他汀的甲醇分解产生甲基-β-D-维西胺。少

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