Molecular Desing and Synthesis of New Bioactive Substances

在过去的两年中，我们对这六个独立的主题进行了研究，并取得了以下成果.将烯基铅试剂合成α-（E&Z）-烯基酮的新方法推广到α-炔基酮的合成。该技术已成功地应用于13，14-二脱氢异碳环素的合成.为了阐明前列环素类似物与PGI_2受体的亲和力，重新检查了类似物6-异卡巴环素的意外低效力。成功地合成了光学活性形式的类似物。血栓调节素的强诱导剂有望成为新的抗血栓药物。由于9-顺式维甲酸的活性远高于其反式异构体，人们合成了几种与环烷烃和杂环固定的9-顺式维甲酸类似物。5元环类似物的活性与9-cis-维甲酸相当.为了建立一种高效、通用的糖基化反应，本文研究了一种基于脱羧糖基化的糖基化反应，该反应具有较好的产率和选择性.由1-脱氢糖和另一种糖形成的原酸酯应该是形成糖基键的良好资源。还原裂解一个C-O键将得到相应的糖苷。一项调查得出了极好的结果。立体化学定义的多羟基环己酮类化合物是合成生物活性物质的重要中间体之一。本文研究了由糖环转化为多羟基环己酮的有效而实用的方法，确定了用催化量的PdCl_2使反应顺利进行。

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。