Molecular Design and Synthesis of Biologically Important Substances

重要生物学物质的分子设计与合成

基本信息

批准号：
05453184
负责人：
IKEGAMI Shiro
金额：
$ 4.61万
依托单位：
Teikyo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

项目摘要

Our major research projects concerm the molecular design of biologically useful and important substances related to the endogenous substances and their synthesis and biological evaluations. Development of new synthetic reactions using oarganometallics such as organolead reagents and asymmetric catalytic reactions is also involved.1. In connection of exploiting biologically important substances, we succeeded in the synthesis of Isocarbacyclin which is most promising prostacyclin analogue as new drug. 6-Isocarbacyclin, which will be expected as its antagonistic activity, has been another target for examination of the styuctureactivity relationship. Thus, we accomplished the synthesis of it as racemic and optically active forms. Biological evaluation is currently under a way.2. Organolead reagents will be useful tools for synthetic organic reactions. One of the inportant subject must be the direct introduction of PG omega-chain to beta-keto esters in PG synthesis. After many trials of the reactions based on Pinhey's work, new synthetic methodology for the general procedure of alpha- (E & Z) -1-alkenyl ketons has been established with the combined operation of an efficient decarboxylation reaction. The versatile synthetic method of alpha-alkynyl ketones has also been developed with the similar manner.3. One of key subjects in sugar chemistry must be the development of an efficient and stereoselective glycosidation which is high versatility with a wide range of applicability. We are challenging now a new methodology with new concepts of glycosidation. An efficient transformation of sugars into synthetically useful intermediates could be developed by employing Pd (II) catalyzed reaction.

我们的主要研究项目涉及与内源性物质相关的具有生物学意义的重要物质的分子设计及其合成和生物学评价。还涉及使用有机金属化合物（例如有机铅试剂）和不对称催化反应等新合成反应的开发。 1．在开发具有重要生物学意义的物质方面，我们成功合成了最有前途的前列环素类似物新药异卡巴环素。 6-异卡巴环素因其拮抗活性而被期待，已成为研究结构活性关系的另一个目标。因此，我们完成了它的外消旋和光学活性形式的合成。目前生物学评价正在进行中。 2．有机铅试剂将成为合成有机反应的有用工具。重要的课题之一必然是在PG合成中将PG omega链直接引入到β-酮酯中。经过对 Pinhey 工作的多次反应试验，结合高效脱羧反应的操作，建立了 α-(E & Z)-1-烯基酮一般程序的新合成方法。以类似的方式也开发了α-炔基酮的通用合成方法。 3．糖化学的关键课题之一必须是开发一种高效、立体选择性的糖苷化方法，该方法具有高通用性和广泛的适用性。我们现在正在挑战一种具有新糖苷化概念的新方法。通过采用 Pd (II) 催化反应，可以开发将糖有效转化为合成有用的中间体的方法。