New Silacyclic Platforms for Complex Target Synthesis

描述(由申请人提供)：该计划的主要目标是开发高效、完全立体控制和实用的合成策略，以利用现成的硅环平台来开发复杂的生物活性靶标。通过对映体选择性去对称化组装，硅环戊烷和硅环己烷为许多具有生物医学意义的天然产物中发现的一系列合成有价值的构建块提供了新的入口。此外，适当官能化的硅环支架将催生具有广泛合成用途的新型不对称催化剂。在拟议的四年授权期内，我们将专注于以下具体目标：(A)利用功能化的五元和六元硅烷开发新的立体选择性转化；(B)设计高度收敛的制霉菌素A1的合成；(C)开发一种完全立体可控的新赫巴因A的合成；(D)开发快速合成PF1018的路线；(E)合理设计手性硅基Lewis酸催化剂。在广泛的初步结果的支持下，这一全面的研究计划旨在通过创新和有效地使用新型硅环模板来促进现代有机合成的最先进水平。

DESCRIPTION (provided by applicant): With the main emphasis on innovation, the primary objective of this program is to develop highly efficient, fully stereocontrolled, and practical synthetic strategies to complex bioactive targets utilizing readily available silacyclic platforms. Assembled via enantioselective desymmetrization, silacyclopentanes and silacyclohexanes provide new entries into a range of synthetically valuable building blocks found in many natural products of biomedical significance. In addition, appropriately functionalized silacyclic scaffolds will lead to new classes of asymmetric catalysts of broad synthetic utility. Within the proposed four-year grant period, we will concentrate on the following specific objectives: (a) development of new stereoselective transformations utilizing functionalized five- and six-membered silanes; (b) design of a highly convergent synthesis of nystatin A1; (c) development of a fully stereocontrolled synthesis of neodysiherbaine A; (d) development of expeditious route to PF1018; (e) rational design of chiral silicon-based Lewis acid catalysts. Supported by extensive preliminary results, this comprehensive research program is aimed at advancing the state-of-the-art of modern organic synthesis through innovative and efficient use of novel silacycles templates.