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The synthesis of a novel calcium ionophore on the model of pamamycin, an aerial mycelium-inducing factor of actinomyces.

在帕马霉素（一种放线菌气生菌丝体诱导因子）模型上合成新型钙离子载体。

基本信息

批准号：
05660117
负责人：
HARA Osamu
金额：
$ 1.41万
依托单位：
NAGOYA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
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

The three dimensional structure of pamamycin, classified as an armed macrocyclo compound, seemed to be a good model to develop a novel calcium ionophore. First of all, various synthetic macrolides were prepared from racemic homononactic acid obtained from alkaline hydrosis of polynactins. The 16-membered macrodiolides, which have an anti-relationship between the ether linkage of THF and the adjacent methyl, showed the cation-binding ability for Na^+ and Li^+. The compound may have a satisfactory basic structure in which this particular calcium ionophore might occur. Also this result made it necessary to synthesize an optically active compound in order to conformational analysis of a novel ionophore. Our synthetic study on optically active hydroxylic acid by use of asymmetric dihydroxylation reaction is undergoing. The synthetic study also contains the step of stereoselective construction of E-olefin for getting a highly enantiomeric pure compound. This problem was already overcome by the application of [2,3] -Wittig reaction, which gave not only E-olefin, but also Z-olefin. And the resulting compound has an allylsilane moiety which is very useful intermediate in organic synthesis. The investigation of the regio-and stereoselective introduction of side chain to macrolide was carried out with aldol reaction or alkylation for the synthesis of pamamycin related compounds. The aldol reaction with boron reagent gave high yields and the highest regio-and stereoselectivity. On the basis of these results, related studies on armed macrocyclo compound are under way, including development of a new guest for not only calcium cations but also other divalent cations.

帕霉素是一种大环化合物，它的三维结构为开发新型钙离子载体提供了一个很好的模型。首先，以聚内酰胺碱水解得到的外消旋高单乳酸为原料，合成了多种大环内酯类化合物。四氢呋喃的醚键与相邻的甲基之间存在反键关系的16元大二内酯对Na^+和Li^+具有阳离子结合能力。该化合物可能具有令人满意的基本结构，其中可能存在这种特定的钙离子载体。这一结果也使得有必要合成一种光学活性的化合物，以便对一种新型离子载体进行构象分析。我们正在进行利用不对称双羟基化反应合成光学活性羟基酸的研究。合成研究还包括立体选择性地构建E-烯烃的步骤，以获得高对映体纯度的化合物。[2，3] -Wittig反应的应用已经克服了这个问题，它不仅产生E-烯烃，而且还产生Z-烯烃。并且所得化合物具有烯丙基硅烷部分，其在有机合成中是非常有用的中间体。研究了通过羟醛缩合反应或烷基化反应在大环内酯上区域和立体选择性引入侧链，合成帕霉素相关化合物。用硼试剂进行的羟醛缩合反应具有较高的产率和区域选择性。在这些结果的基础上，对武装大环化合物的相关研究正在进行中，包括开发不仅针对钙阳离子而且针对其他二价阳离子的新客体。