Strained Silacycle-Mediated Synthesis of Bioactive Rings

描述（由申请人提供）：该提案概述了使用应变手性硅杂环对映选择性合成生物活性吡咯烷和氮杂环丙烷，以及将氮杂环丙烷对映选择性转化为生物重要结构。这些新方法的一个主要目标是解决吡咯烷和氮杂环丙烷结构中一些未解决的问题。T细胞癌和高血压的非天然药物靶点将被讨论，以展示这些方法对生物活性含氮环合成的实用性。此外，对映体选择性的方法，以几种天然产物，包括细胞毒性放线菌素（在肿瘤细胞系代表胃癌，肝癌和乳腺癌的活性）和丝氨酸蛋白酶抑制aerodosins和microcin SF608。应变硅杂内酯介导的氮杂环丙烷的不对称开环反应是合成重要的非天然氨基酸的有效方法。通过使有效的和对映体选择性地访问这些结构，在这个建议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.