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

帕马霉素是一种大环化合物，其三维结构似乎是开发新型钙离子载体的一个很好的模型。首先，以多环鸟苷碱水解得到的外消旋高浓酸为原料，制备了多种合成的大环内酯类化合物。与四氢呋喃的醚键相反的16元大二内酯对Na~(++)和Li~(2+)具有阳离子结合能力。该化合物可以具有令人满意的基本结构，在该基本结构中可以出现这种特殊的钙离子载体。此外，这一结果也使得合成光学活性化合物以进行新型离子载体的构象分析成为必要。我们利用不对称双羟基化反应合成光学活性羟酸的研究正在进行中。合成研究还包括E-烯烃的立体选择性构筑步骤，以获得高对映体纯化合物。这个问题已经被[2，3]-Wittig反应的应用所克服，该反应不仅得到了E-烯烃，而且还得到了Z-烯烃。生成的化合物含有烯丙基硅烷部分，这在有机合成中是非常有用的中间体。通过羟醛缩合或烷基化反应，对大环内酯类化合物的区域和立体选择性引入进行了研究，合成了帕马霉素相关化合物。Aldol与硼试剂的反应产率高，区域和立体选择性最高。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，包括开发一种不仅适用于钙离子，也适用于其他二价阳离子的新客体。

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.