Strained Silacycle-Mediated Synthesis of Bioactive Rings

描述（由申请人提供）：本提案概述了使用张力手性硅环对映选择性合成生物活性吡咯烷和氮杂环，以及氮杂环对映选择性转化为重要的生物结构。这些新方法的一个主要目标是解决一些在吡咯烷和叠氮嘧啶的结构中尚未解决的问题。将讨论t细胞癌和高血压的非自然药物靶点，以展示这些方法在合成生物活性含氮环方面的效用。此外，将介绍几种天然产物的对映选择性方法，包括细胞毒性放线菌素（在代表胃癌、肝癌和乳腺癌的肿瘤细胞系中活跃）和丝氨酸蛋白酶抑制铜绿蛋白苷和微霉素SF608。张力硅环介导的氮杂环对映选择性开孔是合成重要的非天然氨基酸的有效方法。通过对这些结构进行高效和对映选择性的访问，本提案中开发的合成程序将有助于化学家在分子水平上研究生物系统的能力。

DESCRIPTION (provided by applicant): This proposal outlines the use of strained chiral silacycles for the enantioselective synthesis of biologically active pyrrolidines and aziridines, and the enantioselective conversion of aziridines to biologically important structures. One main goal of these new methods will be to address some of the unsolved problems in the construction of pyrrolidines and aziridines. Unnatural drug targets for T-cell cancers and hypertension will be discussed to showcase the utility of these methodologies toward the synthesis of biologically active nitrogen-containing rings. In addition, enantioselective approaches to several natural products will be presented, including the cytotoxic actinomycins (active in tumor cell lines representing stomach, liver, and breast cancer) and the serine protease inhibiting aeruginosins and microcin SF608. Strained silacycle- mediated enantioselective opening of aziridines is proposed as an efficient method for synthesizing biologically important unnatural amino acids. By enabling efficient and enantioselective access to these structures, the synthetic program developed in this proposal will contribute to the ability of chemists to study biological systems at a molecular level.