Catalytic Asymmetric Total Synthesis of (-)- Saudin

描述（由申请人提供）：该提案概述了二萜沙丁的催化不对称合成。沙特恩是一种新型的、密集功能化的笼状双(缩酮)，在小鼠和大鼠中具有显着的体内降血糖活性。该合成的一个关键组成部分是使用催化剂控制来设置与缩酮系统无关的五个立体中心中的三个，包括存在于天然产物中两个季碳上的立体中心。为了完成所提出的路线，将开发一种新的金属催化的未活化烯烃的羧基乙酰氧基化反应，并将其应用于核心结构中包含的β-羟基γ-内酯部分的生成。此外，该项目将通过将其应用于扩展烯醇化物系统的区域和非对映选择性烯丙基化，进一步扩大 Stoltz 实验室最近报道的对映选择性 Tsuji 烯丙基化的范围。通过使用saudin作为发现和开发上述反应的平台，将产生对合成界具有重要实用性的新方法。

DESCRIPTION (provided by applicant): This proposal outlines the catalytic asymmetric synthesis of the diterpene saudin. Saudin is a novel and densely functionalized caged bis(ketal) possessing significant in vivo hypoglycemic activity in mice and rats. A key component of this synthesis will be the use of catalyst control to set three of the five stereocenters not associated with the ketal system, including those present at the two quaternary carbons in the natural product. To accomplish the proposed route, a new metal-catalyzed carboxyacetoxylation of unactivated olefins will be developed and applied to the generation of the beta-hydroxy gamma-lactone moiety contained in the core structure. Additionally, this project will serve to further expand the scope of the recently reported enantioselective Tsuji allylation from the Stoltz laboratories through its application to the regio- and diastereoselective allylation of an extended enolate system. By using saudin as a platform for the discovery and development of the reactions described above, new methodology of significant utility to the synthetic community will be generated.