Desymmetrization of a centrosymmetric diepoxide: Efficient synthesis of a key intermediate in a total synthesis of hemibrevetoxin B
Desymmetrization of a centrosymmetric diepoxide: Efficient synthesis of a key intermediate in a total synthesis of hemibrevetoxin B
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DOI：
10.1021/jo026456b
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发表时间：
2003-02-07
影响因子：
3.6
通讯作者：
Nelson, A
中科院分区：
文献类型：
--
作者：
Holland, JM;Lewis, M;Nelson, A
描述了半毒毒素B全合成中已建立的中间体的制备。酸催化的反式4,5-环氧辛烷-2,7-二酮的环化表现出有价值的动力学和热力学控制的混合：立体定向环氧化物开孔后，产物平衡生成所需的反式八氢吡喃[3,2-b]吡喃环体系。通过缩醛取代、臭氧分解和硫酰化介导的双向精化，得到了中心对称的二氧化物。合成的关键步骤是在天然产物合成中中心对称分子的第一次去对称化：Jacobsen不对称环氧化物水解和丙酮化在两个步骤中以97%的收率和95%的ee获得了已知的合成中间体。天然产物AB环对称中心的利用大大提高了合成效率（8步，总收率34%）。
The preparation of an established intermediate in a total synthesis of hemibrevetoxin B is described. The acid-catalyzed cyclization of trans-4,5-epoxyoctane-2,7-dione exhibited a valuable mixture of kinetic and thermodynamic control: stereospecific epoxide opening was followed by equilibration of the products to provide the required trans-fused octahydropyrano[3,2-b]pyran ring system. Two-directional elaboration, by acetal substitution, ozonolysis, and sulfur ylide-mediated epoxidation, provided a centrosymmetric diepoxide. The key step of the synthesis was the first desymmetrization of a centrosymmetric molecule in natural product synthesis: Jacobsen asymmetric epoxide hydrolysis and acetonization provided the known synthetic intermediate in 97% yield and >95% ee over two steps. The exploitation of the center of symmetry of the AB ring system of the natural product contributed greatly to the efficiency (eight steps, 34% overall yield) of the synthesis.