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

针对基于手性恶唑硼烷酮促进的不对称羟醛缩合反应策略实现多烯大环内酯类化合物FIIPIN 111全合成的问题，开展了这方面的研究，取得了一些有益的结果。使用Aldol反应合成了可用于8个迭代的1.3-多元醇(聚醋酸酯体系)的起始醛，并报道了(四面体：不对称1999)。这与Rychnovsky等人在不对称夏普莱斯氧化的基础上合成该产物的结果一致。从而证明了我们的技术的有效性。此外，通过重复使用不对称Aldol反应的非常简单的技术，考察了以下1，3-多元醇的引入反应。用同样的方法合成了7个重复的1，3-Synn-多元醇。已经证实，无论现有的不对称中心如何，能够引入新的不对称中心的方法在NOT…中是有效的更多的只有FILIPIN III的用途，还有链骨架，包括各种1，3-syn和反系统。然而，虽然直线合成法的选择性可靠，实验步骤方便，但在直链太长的情况下，对合成的总收率来说是无效的。然后尝试了一种收敛的方法，利用我们的不对称Aldol反应合成了两个1.3元醇单元，并尝试了单元之间的缩合反应。该平行合成方法显著提高了合成的总收率。该缩合反应是利用我们先前开发的硅烯醇醚的不对称羟醛缩合反应进行的。通过高度受控的不对称Aldol反应，结合不对称还原反应，可以得到1，3-二醇。通过在最后一步中应用该反应，实现了包括非利平III的所有多元醇部分的不对称合成(四面体Lett。2000)。目前，总合成正在完成。较少

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