C-C Bond Cleavage of α-Pinene Derivatives Prepared from Carvone as a General Strategy for Complex Molecule Synthesis.
C-C Bond Cleavage of α-Pinene Derivatives Prepared from Carvone as a General Strategy for Complex Molecule Synthesis.
复制标题
DOI：
10.1021/acs.accounts.1c00783
复制
发表时间：
2022-03-01
影响因子：
18.3
通讯作者：
Sarpong, Richmond
中科院分区：
文献类型：
--
作者：
Lusi, Robert F.;Perea, Melecio A.;Sarpong, Richmond
复杂分子的制备（例如，生物活性次级代谢物）仍然是化学合成中的重要目标。凭借其复杂的结构，复杂的天然产物激发了全合成运动，可以导致构建分子的全新方式。在二十世纪，出现的一种这样的范例是使用天然存在的“手性池萜烯”作为全合成的起始材料。这些廉价且天然丰富的分子为天然产物的对映体特异性制备提供了容易获得的对映体富集材料来源。手性池萜烯最常见的应用是在合成中，其中它们的结构可以完全或大部分直接叠加到目标结构的一部分上。较不直接的用途，其中起始手性池萜烯的结构在靶标的结构中不是立即明显的，实施起来可能更具挑战性。然而，这些“非直观”的方法说明了最终的承诺，手性池为基础的战略：任何单一的手性池萜烯可以应用于合成的一个不确定数量的结构多样的复杂的合成目标。根据定义，这种策略需要仔细协调C-C键形成和C-C裂解反应的序列，这导致萜烯结构的重塑。传统的重排化学和过渡金属催化的C─C裂解方法的结合，后者主要是在世纪早期发展起来的，为实施这种重塑方法提供了丰富而强大的工具箱。在这篇文章中，我们详细介绍了我们在香芹酮（一种手性池萜）的骨骼重塑中使用各种C─C裂解策略的努力。这种骨骼重塑策略使香芹酮支架重组成具有各种碳骨架的合成中间体，然后，我们利用这些碳骨架来合成结构不同的萜烯天然产物。我们开始描述我们的初步调查，各种不同的，机械上不同的C-C裂解过程涉及环丁醇合成香芹酮。这些初步的研究表明，如何亲电介导的semipinacol重排这些环丁醇可以导致[2.2.1]双环中间体，以及如何Rh和Pd催化的C─C裂解可以导致各种密集官能化的环己烯有关的天然产物的合成。然后，我们提出了几个总的合成使用这些合成中间体，开始与桥接，多环倍半萜longiterrane，这是从香芹酮衍生的[2.2.1]双环以下的关键semipinacol重排合成。接下来，我们讨论了大环磷菌素家族的几个成员是如何从环己烯衍生物通过铑催化的C─C裂解反应合成的。最后，我们描述了我们的海洋二萜xishacorene B的合成，其是使用关键的Pd催化的C─C裂解/交叉偶联来制备的，该裂解/交叉偶联促进了天然产物结构中的核心[3.3.1]双环的组装。
The preparation of complex molecules (e.g., biologically active secondary metabolites) remains an important pursuit in chemical synthesis. By virtue of their sophisticated architectures, complex natural products inspire total synthesis campaigns that can lead to completely new ways of building molecules. In the twentieth century, one such paradigm which emerged was the use of naturally occurring “chiral pool terpenes” as starting materials for total synthesis. These inexpensive and naturally abundant molecules provide an easily accessed source of enantioenriched material for the enantiospecific preparation of natural products. The most common applications of chiral pool terpenes are in syntheses where their structure can, entirely or largely, be superimposed directly onto a portion of the target structure. Less straightforward uses, where the structure of the starting chiral pool terpene is not immediately evident in the structure of the target, can be more challenging to implement. Nevertheless, these “nonintuitive” approaches illustrate the ultimate promise of chiral pool-based strategies: that any single chiral pool terpene could be applied to syntheses of an indefinite number of structurally diverse complex synthetic targets. By definition, such strategies require carefully orchestrated sequences of C─C bond forming and C─C cleaving reactions which result in remodeling of the terpene architecture. The combination of traditional rearrangement chemistry and transition-metalcatalyzed C─C cleavage methods, the latter of which were primarily developed in the early twenty-first century, provide a rich and powerful toolbox for implementing this remodeling approach. In this Account, we detail our efforts to use a variety of C─C cleavage tactics in the skeletal remodeling of carvone, a chiral pool terpene. This skeletal remodeling strategy enabled the reorganization of the carvone scaffold into synthetic intermediates with a variety of carboskeletons, which we, then, leveraged for the total syntheses of structurally disparate terpene natural products. We begin by describing our initial investigations into various, mechanistically distinct C─C cleavage processes involving cyclobutanols synthesized from carvone. These initial studies showcased how electrophile-mediated semipinacol rearrangements of these cyclobutanols can lead to [2.2.1]bicyclic intermediates, and how Rh- and Pd-catalyzed C─C cleavage can lead to a variety of densely functionalized cyclohexenes pertinent to natural product synthesis. We, then, present several total syntheses using these synthetic intermediates, beginning with the bridged, polycyclic sesquiterpenoid longiborneol, which was synthesized from a carvone-derived [2.2.1]bicycle following a key semipinacol rearrangement. Next, we discuss how several members of the macrocyclic phomactin family were synthesized from a cyclohexene derivative prepared through a Rh-catalyzed C─C cleavage reaction. Finally, we describe our synthesis of the marine diterpene xishacorene B, which was prepared using a key Pd-catalyzed C─C cleavage/cross-coupling that facilitated the assembly of the core [3.3.1]bicycle that is resident in the natural product structure.
登录
查看更多内容
影响因子：
62.1
作者：
Brill ZG;Condakes ML;Ting CP;Maimone TJ
通讯作者：
Maimone TJ
影响因子：
64.8
作者：
Marth CJ;Gallego GM;Lee JC;Lebold TP;Kulyk S;Kou KG;Qin J;Lilien R;Sarpong R
通讯作者：
Sarpong R
影响因子：
2.1
作者：
Bermejo, Francisco A.;Fernandez Mateos, Alfonso;Rubio Gonzalez, Rosa
通讯作者：
Rubio Gonzalez, Rosa
影响因子：
15
作者：
Ishida, Naoki;Sawano, Shota;Murakami, Masahiro
通讯作者：
Murakami, Masahiro
影响因子：
5.1
作者：
Bahadoor, Adilah;Schneiderman, Danielle;Harris, Linda J.
通讯作者：
Harris, Linda J.