Development of the synthetic study of polyene macrolides by the strategy based on completely controlled 1,3-diol synthesis

针对以手性恶唑硼烷酮促进的不对称醛醇反应为策略实现多烯大环内酯filipin 111的全合成问题，开展了相关研究，并取得了一些有益的结果。用醛醇反应合成了可用于8次迭代1.3多元醇（聚醋酸酯体系）的起始醛，并被报道（Tetrahedron: symmetry 1999）。这与Rychnovsky等人在不对称Sharpless氧化的基础上合成产物的结果一致。这样就证明了我们技术的有效性。此外，通过重复使用不对称醛醇反应，用非常简单的技术考察了1,3-多元醇的引入反应。用同样的方法合成了7个迭代1,3-同步多元醇。结果表明，该方法能够在现有不对称中心的情况下引入新的不对称中心，不仅适用于非对称中心，而且适用于包括各种1,3-顺、反体系在内的链骨架。然而，尽管直线合成方法在选择性上是可以信赖的，而且实验步骤也很方便，但在直链过长的情况下，人们认为直线合成方法在合成的总收率上并不有效。采用不对称醛醇反应制备了两个1.3多元醇单元，并进行了缩合实验。采用平行法可显著提高合成的总收率。该缩合反应是利用我们先前开发的不对称醛醇与硅烯醇醚的反应进行的。高度控制的不对称醛醇反应，伴随着不对称还原，可以得到1,3-辛二醇。通过在最后阶段应用该反应，实现了包括filipin III的所有多元醇部分的不对称合成（Tetrahedron Lett. 2000）。目前，全合成正在完成。少

For the problem to achieve the total synthesis of polyene macrolide filipin 111 by the strategy based on chiral oxazaborolidinone-promoted asymmetric aldol reactions, the research was developed with some useful results. The synthesis of the starting aldehyde available for the 8 iterative 1.3-polyol (polyacetate systems) by using the aldol reactions was completed and was reported (Tetrahedron: Asymmetry 1999). It agreed with the result of synthesizing the product on the basis of the asymmetric Sharpless oxidation by Rychnovsky et al . And thus the effectiveness of our technique was shown. In addition, the following introduction reaction of 1,3-polyol was examined by the very simple technique with repetitive use of the asymmetric aldol reaction. The asymmetric synthesis of 7 iterative 1,3-syn-polyol was performed by the same technique. It was confirmed that the methodology which enables that new asymmetric center is introduced regardless of existing asymmetric centers is effective in not … More only filipin III of the purpose but also chain skeleton including various 1,3-syn and anti systems. However, though the rectilinear synthetic method is able to be trusted in the selectivity and the experimental procedure is convenient, in the case of the too long straight chain it was judged not to be efficient on the overall yield of the synthesis. Then a convergent approach was tried Two 1.3-polyol units were prepared by using our asymmetric aldol reaction, and the condensation between the units was tried. The total yield of the synthesis was remarkably improved by the parallel method. The condensation was carried out by using the asymmetric aldol reaction with silyl enol ether previously developed by us. The highly controlled asymmetric aldol reaction, accompanied with an asymmetric reduction can give a 1,3-syn-diol. By applying this reaction in the last stage, the asymmetric synthesis of a segment including all polyol parts of filipin III was achieved (Tetrahedron Lett. 2000). At present, the total synthesis is being completed. Less