Studies of New Reactivity for Efficient Strategies Toward Bioactive Natural Products

通过这一奖项，化学合成计划资助印第安纳大学化学系的David R.Williams教授探索戊二烯基碳负离子的电环化反应行为。所提出的方法将阐明导致电环闭合的反应性，这提供了获得独特环系的有效途径。初步研究将为研究立体选择性的Rh催化的氢酰化反应和铁催化的Pauson-Khandd过程的串联反应提供底物。这些转化以现有技术难以获得或尚未达到的结构的有效分子组装为目标。将这些分子框架包括在天然抗肿瘤抗生素和最近发现的海洋天然产品中，为拟议的研究提供了额外的意义。此外，这些研究将有助于更好地理解提出的关键反应的反应性、范围和机制。拟议研究计划的成功开发将影响制药、化学和农业行业对化学合成新方法和战略的需求。该项目将向本科生和研究生提供针对生物学相关目标的复杂现代合成培训，包括在强调学术和创造力的支持性环境中代表不足的少数族裔。

With this award, the Chemical Synthesis Program is funding Professor David R. Williams of the Department of Chemistry at Indiana University to explore the behavior of electrocyclization reactions of pentadienyl carbanions. The proposed methodologies will elucidate reactivity leading to electrocyclic ring closures which provide efficient access to unique ring systems. Initial studies will generate substrates for investigations of tandem reactions of stereoselective rhodium-catalyzed hydroacylations and iron-catalyzed Pauson-Khand processes. These transformations target the efficient molecular assembly of architectures that are difficult to access or as yet unattained by the prior art. The inclusion of these molecular frameworks in naturally-occurring antitumor antibiotics and recently discovered marine natural products provides additional significance for the proposed studies. Moreover, these studies will contribute a better understanding of the reactivity, scope, and mechanisms of the key proposed reactions. Successful development of the proposed research plan will impact the need for new methodologies and strategies for chemical synthesis in the pharmaceutical, chemical, and agricultural industries. The project will provide training in sophisticated modern synthesis toward biologically relevant targets to both undergraduate and graduate students, including underrepresented minorities in a supportive environment emphasizing scholarship and creativity.