A "Chiral aldehyde" equivalent as a building block towards biologically active targets
A "Chiral aldehyde" equivalent as a building block towards biologically active targets
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DOI：
10.1002/chem.200305634
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发表时间：
2004-05-03
影响因子：
4.3
通讯作者：
Crawley, ML
中科院分区：
文献类型：
--
作者：
Trost, BM;Crawley, ML
手性γ-芳氧基丁烯内酯，容易获得通过动态动力学不对称转化（DYKAT）的外消旋酰氧基丁烯内酯，被用作分子间环加成和迈克尔反应的“手性醛”的积木。前所未有的选择性，在三亚甲基甲烷环加成与这种积木允许一种新的代谢型谷氨酸受体1拮抗剂的拜耳公司开发的有效合成。这些研究进一步激发了最终全合成（+）布雷菲德菌素A的工作，布雷菲德菌素A是一种具有一系列重要生物学特性的天然产物。该目标分子中的所有立体化学均来自两个钯催化的不对称烯丙基烷基化反应。反式烯烃的合成通过Julia烯化反应和一种季铵盐催化的反式硅氢加成-脱硅反应方案。（+）-布雷菲德菌素A的合成路线适合于类似物合成，并在18个步骤中以6%的总产率完成。
Chiral gamma-aryloxybutenolides, readily accessible through dynamic kinetic asymmetric transformation (DYKAT) of racemic acyloxybutenolides, were utilized as "chiral aldehyde" building blocks for intermolecular cycloadditions and Michael reactions. Unprecedented selectivity in trimethylenemethane cycloadditions with this building block allowed an efficient synthesis of a novel metabotropic gluta mate receptor 1 antagonist in development by the Bayer corporation. These studies further inspired work that culminated in the total synthesis of (+)brefeldin A, a natural product with a range of significant biological proper ties. All of the stereochemistry in this target molecule was derived from two palladium-catalyzed asymmetric allylic alkylation reactions. The trans-alkenes were synthesized by a Julia olefination and a ruthenium-catalyzed trans-hydrosilylation-protodesilylation protocol. The route to (+)-brefeldin A lends itself to analogue syntheses and was completed in 18 steps in 6% overall yield.