Synthesis of (-)-Terpestacin Via Cyclopentannelation

描述(申请人提供)：拟议的研究涉及HIV病毒的细胞抑制物(-)-Terpestin的全合成。主要目标是基于两种强大的方法，不对称环戊烯基化和环合复分解，得到一个简短、收敛的合成方法。TIUS集团开发的不对称环戊烯基化反应提供了Terpestain的核心复杂的手性环戊酮。目标将被组装成两块，在合成后期连接起来，然后使用烯烃复分解环化。不对称环戊烯基化反应在快速合成复杂的手性环戊酮和高立体纯度方面显示出巨大的潜力。该方法正在不断改进，包括开发新的更强大的手性助剂，该项目是一个很好的应用。环合复分解反应已迅速成为大环化反应的主流方法。仍然存在的一些主要挑战是指导在竞争反应烯烃存在下的烯化反应的区域专一性，以及操纵最终烯烃形成的立体选择性。这条拟议的合成路线最终将在其他人在场的情况下使两种残留的烯烃进行烯化反应。所需烯化反应的选择性是基于Nicolaou小组引入的空间操作。该项目是这一区域控制战略的延伸试验场。最后，该项目代表了方法学开发和全合成的良好二分法，最终形成了一种快速生产这种可能的抗艾滋病毒药物的方法。

DESCRIPTION (provided by applicant): The proposed research involves the total synthesis of (-)-Terpestacin, a cellular inhibitor of the HIV virus. The primary goal is a brief, convergent synthesis anchored upon two powerful methodologies, asymmetric cyclopentannelation and ring closing metathesis. Asymmetric cyclopentannelation, developed by the Tius group, delivers complex chiral cyclopentanones, the core of Terpestacin. The target will be assembled in two pieces to be connected late in the synthesis and then cyclized using olefin metathesis. Asymmetric cyclopentannelation has demonstrated remarkable potential at delivering complex chiral cyclopentanones rapidly and in high stereopurity. The methodology is under continuing refinement including the development of new more powerful chiral auxiliaries for which this project serves as an excellent application. Ring closing metathesis has quickly become a mainstay method of macrocyclization. Some of the major challenges that still exist are the directing the regiospecificity of the olefination in the presence of competing reacting alkenes as well as the manipulation of the stereoselectivity of the final alkene formation. This proposed synthetic route would culminate with the olefination of two resident olefins in the presence of others. The selectivity for the desired olefination is based upon steric manipulations introduced by the Nicolaou group. This project represents an extended proving ground for this strategy of regiocontrol. Finally, the project represents a nice dichotomy of methodology development and total synthesis culminating in a rapid means of producing this possible anti-HIV drug.