Bio-organic Chemistry Laboratory, Institut de Recherches Cliniques de Montréal, 110 Avenue des Pins Ouest, Montréal, Québec, Canada H2W 1R7.
J Org Chem. 2011 Oct 7;76(19):7654-76. doi: 10.1021/jo2013884. Epub 2011 Sep 6.
The structure-activity study of a bioactive natural product containing polypropionate subunits requires that its stereoisomers also be evaluated. Therefore, a general approach to synthesize these motifs is necessary. We describe herein the synthesis of the C1-C13 polypropionate subunit of zincophorin and isomers thereof using a two-reaction sequence: an aldol reaction using a mixture of tetrasubstituted enoxysilanes and a hydrogen-transfer reaction, both under Lewis acid control. Selection of the appropriate Lewis acid dictates the stereochemical outcome of these reactions. From a tactical standpoint, this study shows how a polypropionate sequence can be read and constructed in two directions, either the east-west or the west-east approaches. The choice of the optimal route is influenced by the number of complexation sites that can interfere in the aldol step under bidentate Lewis acid control.
含有聚丙酸盐亚基的生物活性天然产物的结构-活性研究需要对其立体异构体进行评估。因此，需要一种通用的方法来合成这些结构。本文描述了使用两步反应序列（醛醇反应和氢转移反应）合成锌蛋白的 C1-C13 聚丙酸盐亚基及其异构体的方法，这两种反应均受路易斯酸控制。选择合适的路易斯酸决定了这些反应的立体化学结果。从策略角度来看，这项研究展示了如何从两个方向读取和构建聚丙酸盐序列，即东西向或西东向方法。最佳路线的选择受可以在双齿路易斯酸控制下的醛醇步骤中干扰的螯合位点数量的影响。
