A Unified Synthetic Approach to the Transtaganolide and Basiliolide Natural Products
A Unified Synthetic Approach to the Transtaganolide and Basiliolide Natural Products
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反马铃薯内酯和罗勒内酯天然产物的统一合成方法
DOI：
10.7907/09dw-p586
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
H. Nelson
中科院分区：
文献类型：
--
作者：
H. Nelson
本文描述了transstaganetin和basiliprin天然产物家族的几个成员的首次全合成。一个通用的策略，铰链上使用的仿生Ireland-Claisen重排/Diels-Alder环加成级联，开发。它允许快速组装最复杂的结构，和生物活性的家庭成员。一个简短的介绍，调查使用吡喃酮狄尔斯-阿尔德环加成在全合成之前，我们的合成工作的细节。通过文献的例子，描述了通过这个反应歧管的结构图案的多样性。我们的实验工作的帐户开始与广泛的模型研究的细节。首先，制备了一个简单的系统，该系统探测了通过分子内吡喃酮Diels-Alder反应构建basilipine B的能力。结果表明，空间拥挤的核心可以构建在一个高度非对映选择性的方式使用这种技术。第二，一个简单的异戊二烯化吡喃酮的构建，并在各种条件下进行了一个简易的爱尔兰-克莱森重排。随后，在级联中利用这两种方法允许快速构建外消旋transstaganlavin C、transstaganlavin D、basilivine B和epi-8-basilivine B。此外，一种新的Pd催化的[5+2]成环技术被用来构建古老的，羧基-烯酮-缩醛的C-环存在于大多数代谢产物。集成到我们的一般战略的不对称性也进行了说明。手性硅烷导向基团的使用使得对映选择性Ireland-Claisen重排的成功和罕见的应用成为可能，最终全合成了（+）-transstagantin C、（-）-transstagantin D、（+）-transstagantin B和（-）-transstagantin A。此外，这项工作对现有的生物合成假说的影响进行了讨论。
Herein are described the first total syntheses of several members of the transtaganolide and basiliolide natural product family. A general strategy, hinging upon the use of a biomimetic Ireland–Claisen rearrangement/Diels–Alder cycloaddition cascade, was developed. It allowed for the rapid assembly of the most structurally complex, and biologically active members of the family. A brief introduction that surveys the use of the pyrone Diels–Alder cycloaddition in total synthesis precedes details of our synthetic efforts. The diversity of structural motifs accessible through this reaction manifold is described through literature examples. The account of our experimental work begins with details of extensive model studies. First, a simple system was prepared which probed the ability to construct basiliolide B via an intramolecular pyrone Diels–Alder reaction. It was demonstrated that the sterically congested core could be constructed in a highly diastereoselective fashion using this technology. Second, a simple prenylated pyrone was constructed, and shown to undergo a facile Ireland–Claisen rearrangement under a variety of conditions. Subsequently, the utilization of these two methods within a cascade allowed for the rapid construction of racemic transtaganolide C, transtaganolide D, basiliolide B, and epi-8-basiliolide B. Furthermore, a novel Pd-catalyzed [5+2] annulation technology is utilized to construct the venerable, carboxy-ketene-acetal containing C-ring present in most of the metabolites. Integration of asymmetry into our general strategy is also described. Utilization of a chiral silane directing group allowed for the successful and rare application of an enantioselective Ireland–Claisen rearrangement, culminating in the total syntheses of (+)- transtaganolide C, (–)-transtaganolide D, (+)-transtaganolide B, and (–)-transtaganolide A. Furthermore, the impact of this work on existing biosynthetic hypotheses is discussed.