Diastereoselective synthesis of 2,3,6-trisubstituted tetrahydropyran-4-ones via prins cyclizations of enecarbamates: A formal synthesis of (+)-ratjadone A
Diastereoselective synthesis of 2,3,6-trisubstituted tetrahydropyran-4-ones via prins cyclizations of enecarbamates: A formal synthesis of (+)-ratjadone A
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DOI：
10.1021/ja046940r
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发表时间：
2004-10-06
影响因子：
15
通讯作者：
Funk, RL
中科院分区：
文献类型：
--
作者：
Cossey, KN;Funk, RL
恩氨基甲酸酯被证明是 Prins 环化的优异终止基团。该方法的一个值得注意的特点是通过金属化(E)-烯氨基甲酸酯与环氧化物的烷基化来简单、立体选择性地构建环化前体。然后以高保真度转移所得三取代(E)-烯氨基甲酸酯的立体化学，以提供天然存在的化合物中经常观察到的且具有生物学意义的全顺式-2,3,6-三取代四氢吡喃亚结构。其它取代的四氢吡喃，包括2,3,5,6-四取代、顺-2,3-二取代和顺-2,6-二取代也是可用的。该方法促进了核输出抑制剂 (+)-ratjadone A 的极其简洁的正式全合成。
Enecarbamates are shown to be excellent terminating groups for Prins cyclizations. A noteworthy feature of this methodology is the easy, stereoselective construction of the cyclization precursors by alkylation of metalated (E)-enecarbamates with epoxides. The stereochemistry of the resultant trisubstituted (E)-enecarbamates is then transferred with high fidelity to afford the frequently observed and biologically significant all-cis-2,3,6-trisubstituted tetrahydropyran substructures of naturally occurring compounds. Other substituted tetrahydropyrans, including 2,3,5,6-tetrasubstituted,cis-2,3-disubstituted, andcis-2,6-disubstituted, are also accessible. This methodology facilitated an exceptionally concise formal total synthesis of the nuclear export inhibitor (+)-ratjadone A.