Asymmetric total syntheses of tuberostemonine, didehydrotuberostemonine, and 13-epituberostemonine
Asymmetric total syntheses of tuberostemonine, didehydrotuberostemonine, and 13-epituberostemonine
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DOI：
10.1021/ja044280k
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发表时间：
2005-01-12
影响因子：
15
通讯作者：
Spencer, SR
中科院分区：
文献类型：
--
作者：
Wipf, P;Spencer, SR
详细的实验方法对五环百部生物碱tuberostemonine和二脱氢tuberostemonine和密切的类似物13-epituberostemonine的描述。合成起始于氢吲哚啉酮衍生物，其可以在一个步骤中从苄氧羰基保护的L-酪氨酸大规模获得。这种氢吲哚啉酮转化为目标结构的亮点是钌催化剂的三重使用，首先在氮杂环庚三烯闭环复分解中，然后在烯烃异构化和交叉复分解丙烯基-乙烯基交换中，以及通过使用锂化的不对称双环[3.2.1]辛烷（ABO）原酸酯将γ-丁内酯环立体选择性连接到四环素核结构上。密度泛函理论（DFT）方法的结构分析表明，天然产物的氧化容易是由于吡咯烷和稠合环己烷环的构象偏好。
Detailed experimental approaches toward the pentacyclic Stemona alkaloids tuberostemonine and didehydrotuberostemonine and the close analogue 13-epituberostemonine are described. The syntheses originate with a hydroindolinone derivative that can be obtained on a large scale in a single step from carbobenzoxy-protected L-tyrosine. Highlights of the conversion of this hydroindolinone to the target structures are the three-fold use of ruthenium catalysts, first in azepine ring-closing metathesis and then in alkene isomerization and cross-metathesis propenyl-vinyl exchange, as well as the stereoselective attachment of a y-butyrolactone ring to a tetracycle core structure by use of a lithiated asymmetric bicyclo[3.2.1]octane (ABO) ortho ester. Structural analysis by density functional theory (DFT) methods revealed that the ease of oxidation of the natural product is likely due to the conformational preferences of the pyrrolidine and the fused cyclohexane rings.