Molecular Desing and Synthesis of New Bioactive Substances

新生物活性物质的分子设计与合成

基本信息

批准号：
07457523
负责人：
IKEGAMI Shiro
金额：
$ 4.67万
依托单位：
Teikyo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

The six independent subjects have been examined for past two research years and the successful resultes we obtained are summarized as follows.1. The new and versatile synnthetic procedure for alpha- (E&Z) -alkenylkentones by emplying alkenyllead reagents has been extended to the preparation of alpha-alkynylketones. An applikation of this technique to the synthesis of 13,14-didehydroisocarbacycline has been used successuflly.2. In order to clarify an affinity power of prostacycline analogues with a PGI_2 reseptor, an unexpectedly low potency of the analogues, 6-Isocarbacycline was reexamined. The analogue was successfully synthesized in the opteically active form.3. A strong inducer of thrombomoduline would be a candidate for new antithrombotic agent. As 9-cis-Retionic acid has more potent activity than its trans isomer, several 9-cis-analogues fixed with cycloalkanes and heterocycles have been syntesized. The analogues with 5-membered rings exhibit an activity equivanlent to 9-cis-Retinoic acid.4. In order to establish an efficient and versatile glycosylation reaction, a conceptionally different glycosylation based on decarboxylative glycosylation was investigate and the procedure gave good results in good yields and selectivity.5. Orthoesters formed from 1-dehydrosugar and another sugar shoul be good resourses for glycosyl bond formation. Reductive cleavage of one of a C-O bond would afford the corresponding glycoside. An investigation gave an excellent result.6. Stereochemically difined polyhydroxylated-cyclohexanones should be one of the most powerful syntheticintermediates for bioactive substances. Efficient and practical procedures for the ring-transformation from sugars to polyhydroxylated cyclohexanones were investigated and it wa established that the reactions proceed smoothly by using a catalytic amount of PdCl_2。

过去两年的研究对六个独立课题进行了研究，我们所获得的成功结果总结如下： 1．利用烯基铅试剂合成α-(E&Z)-烯基烯酮的新的、通用的方法已扩展到α-(E&Z)-烯基烯酮的制备。该技术已应用于 13,14-二脱氢异卡巴环素的合成。 2.为了阐明前列环素类似物与PGI_2受体的亲和力，该类似物的效力出乎意料地低，重新研究了6-异卡巴环素的光学活性形式。3．血栓调节蛋白将成为新型抗血栓剂的候选者，因为 9-顺式维甲酸比其反式具有更有效的活性。异构体，已经合成了几种用环烷烃和杂环固定的9-顺式类似物。具有5元环的类似物表现出与9-顺式视黄酸相当的活性。4．研究了基于脱羧糖基化的概念上不同的糖基化，该方法在良好的产率和选择性方面给出了良好的结果。5． 1-脱氢糖和另一种糖应该是糖基键形成的良好资源，其中一个C-O键的还原断裂将产生相应的糖苷。 6．生物活性物质的合成中间体，用于从糖到多羟基化的环转化的有效且实用的程序。对环己酮进行了研究，发现使用催化量的 PdCl_2 反应可以顺利进行。