Molecular Desing and Synthesis of New Bioactive Substances

在过去两年的研究中，我们对六个独立的受试者进行了检查，并总结了我们获得的成功结果如下：1。采用烯基铅试剂合成α - (E&Z) -烯基酮的新方法已扩展到α -炔基酮的制备。该技术已成功地应用于13,14-二脱氢异环素的合成。为了明确前列环素类似物与PGI_2受体的亲和能力，重新研究了6-异环素类似物的低效性。成功地合成了具有旋光活性的类似物。一种强凝血调节剂可能是新型抗血栓药物的候选物。由于9-顺式反构体比其反式异构体具有更强的活性，因此合成了几种与环烷烃和杂环固定的9-顺式类似物。具有5元环的类似物具有与9-顺式维甲酸相当的活性。为了建立一个高效和通用的糖基化反应，研究了一种基于脱羧糖基化的概念上不同的糖基化反应，该反应在收率和选择性上都很好。由1-脱氢糖和另一种糖形成的正酯应该是糖基键形成的良好资源。一个C-O键的还原裂解会产生相应的糖苷。一项调查得出了极好的结果。立体化学定义的聚羟基化环己酮应该是生物活性物质最强大的合成中间体之一。研究了糖环转化为多羟基环己酮的有效和实用的方法，并确定了使用一定量的PdCl_2催化反应进行顺利。

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。