TOTAL SYNTHESIS OF PSEUDOPTEROLIDE

拟蕨内酯的全合成

• 批准号: 6385108
• 负责人: Alison J Frontier
• 金额: $ 2.3万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-24 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6385108
• 关键词: animal extract; chemical synthesis; coral; cyclization; lactones; marine toxins; neurotoxins; stereochemistry

The proposed synthesis of pseudopterolide addresses several meaningful scientific issues. Pseudopterolide is a natural product with particularly interesting biological activity. It disrupts cell division via a selective mechanism and is cytotoxic at concentrations of 1-10 muo1/M. The highlight of the proposed synthesis is the implementation of an enyne metathesis reaction that should allow the conversion of a cyclophane into the desired strained ring system in one efficient step. One of the goals of the synthesis is to broaden the scope of this metathesis by subjecting new types of substrates to the reaction conditions. This ring-expanding enyne metathesis forms the basis for the assembly of a large ring with several stereocenters, constituting a new synthetic approach to the pseudopterane natural products. Other interesting steps in the proposed route include the diasteroselective macrocyclization of a trichloroallylsilane, an unusual epoxidation sequence, and a stereo- and regioselective coupling reaction proceeding through an apparent pi-allyl nickel complex. Taken together, the chemistry that will be explored over the course of this research will be illuminating, efficient. and most importantly, should result in discoveries that will help to expand the frontiers of synthetic chemistry.

提议的伪蝶膜合成解决了几个有意义的科学问题。 伪蝶呤是一种天然产物，具有特别有趣的生物学活性。 它通过选择性机制破坏细胞分裂，并在1-10 MUO1/m的浓度下具有细胞毒性。 所提出的合成的亮点是实施了Enyne元置反应，该反应应允许在一个有效的步骤中将环粒烷转化为所需的紧张环系统。 合成的目标之一是通过将新类型的底物对反应条件进行新类型的底物范围扩大范围。这种张开环的Enyne元看构成了与几个立体中心组装大环的基础，构成了伪替烷天然产物的新合成方法。提出的途径中的其他有趣步骤包括三氯乙烯的映选择性大环，不寻常的环氧序列以及通过明显的PI-Allyl镍复合物进行进行的立体和区域选择性偶联反应。 综上所述，在这项研究过程中将探索的化学反应将是启发性，有效的。最重要的是，应该导致发现将有助于扩大合成化学的前沿。