Strained Silacycle-Mediated Synthesis of Bioactive Rings

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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.