Synthesis of (-)-Terpestacin Via Cyclopentannelation

通过环戊烷化合成 (-)-Terpestacin

• 批准号: 7049099
• 负责人: GIDEON O BERGER
• 金额: $ 4.4万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-11-16 至 2006-11-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7049099
• 关键词: AIDS therapy; alkylation; antiAIDS agent; antiviral agents; biological products; biotherapeutic agent; chemical synthesis; cyclization; cycloalkene; cyclopentane; drug design /synthesis /production; method development; organic chemicals; stereoisomer

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.

描述（由申请人提供）：拟议的研究涉及（ - ） - Terpestacin（HIV病毒的细胞抑制剂）的总合成。主要目标是锚定在两种强大的方法论上的简短，收敛的合成，即不对称的环绕和环闭合分解。由Tius组开发的不对称环肠道镀术，提供了复杂的手性环戊酮，这是Terpestacin的核心。该靶标将分为两块，以在合成后期连接，然后使用烯烃的元理解。不对称环肠道化表现出在快速和高立体性传递复杂性手性环戊酮方面具有巨大的潜力。该方法正在持续完善，包括开发新的更强大的手性辅助机构，该项目是一个很好的应用。环闭合的分解已迅速成为大环化的主要方法。仍然存在的一些主要挑战是指导在存在竞争反应烯烃的情况下烯烃的重新定义性，以及对最终烷烃形成的立体选择性的操纵。这项提出的合成途径将在其他存在的情况下以两种居民烯烃的烯烯化为顶点。所需烯烃的选择性基于Nicolaou组引入的空间操作。该项目代表了这种策略控制策略的扩展遗嘱基础。最后，该项目代表了方法论开发和总合成的一个不错的二分法，最终是生产这种可能的抗HIV药物的快速方法。