Catalytic Asymmetric Total Synthesis of (-)- Saudin

说明书(申请人提供)：本建议书概述了二萜酱油酸苷的催化不对称合成。沙特蛋白是一种新型的、功能化的笼式双缩酮化合物，在小鼠和大鼠体内具有显著的降血糖活性。这种合成的一个关键组成部分将是使用催化剂控制来设置五个与缩酮系统无关的立体中心中的三个，包括那些存在于天然产物中两个季碳的立体中心。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乙酰氧基化反应，并将其应用于核心结构中含有的β-羟基伽马-内酯部分的生成。此外，该项目将进一步扩大最近报道的Stoltz实验室的Tsuji对映选择性烯丙基化反应的范围，将其应用于扩展的烯醇体系的区域和非对映选择性烯丙基化反应。通过使用沙丁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意义的新方法。

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.