Advances in the Development of Synthetic Methods for Complex Molecule Synthesis

提出的研究计划旨在开发新的策略和新的合成方法和试剂，以有效地形成碳-碳和碳杂原子键。能够以选择性的方式生成产物的方法，无论是位点选择性、化学选择性还是立体选择性的方式，都是特别重要的，因为它们可以用于复杂分子的受控和可预测的合成。******当前提案中概述的具体项目包括环加成，电环化和符号反应的发展。将确定这些方法的范围，并在适当情况下确定反应的机制。此外，了解控制反应性和选择性的参数将有助于建立预测模型。******反应序列和多米诺反应允许使用实际条件和稳定试剂快速构建分子复杂性，具有特别的价值。所开发的合成方法将直接应用于生物相关和结构复杂的靶分子的合成，包括具有抗癌或抗生素活性的天然产物，如大环沉积肽和生物碱。例如，我们的目标是通过电环化方法合成海绵生物碱凝胶蛋白和nagelamide。******一般方法，反应和试剂的广泛适用性最终导致其他合成有机化学家的实际利益，无论是在学术实验室和商业实验室。总的来说，拟议的计划不仅将推进科学技术的基础研究，而且将为对制药，生物技术，医药，农化和高科技材料领域的研究和开发事业感兴趣的学生提供培训和研究环境

The proposed research program is aimed at the development of novel strategies and new synthetic methods and reagents for the efficient formation of carbon-carbon and carbon-heteroatom bonds. Methods that can generate products in a selective manner, whether in a site-selective, chemoselective or stereoselective fashion are of particular importance, since they can then be used for the controlled and predictable synthesis of complex molecules. ******Specific projects outlined in the current proposal include the development of cycloaddition, electrocyclization and sigmatropic reactions. The scope of these methods and, where appropriate, the mechanism of the reactions will be determined. In addition, obtaining an understanding of the parameters which control reactivity and selectivity will allow the development of predictive models.******Reaction sequences and domino reactions that allow for the rapid construction of molecular complexity using practical conditions and stable reagents are of particular value. The synthetic methods that are developed will be applied directly to the syntheses of biologically relevant and structurally complex target molecules, including natural products which display anticancer or antibiotic activity, such as macrocyclic depsipeptides and alkaloids. Example targets are the marine sponge alkaloids agelamadin and nagelamide which we aim to synthesize through an electrocyclization approach. ******General methods, reactions, and reagents that are of broad applicability ultimately result in practical benefits to other synthetic organic chemists, both in academic labs and commercial labs. Overall the proposed program will not only advance basic research in science and technology, but will also provide a training and research environment for students interested in research and development careers in the pharmaceutical, biotechnology, medicinal, agrochemical, and high-tech materials sectors.**