Assessing Ligand vs Ligandless Catalysis to Simplify Chemical Transformations and Drug Discovery

项目总结 检测新的微生物菌株和耐药细菌需要在以下方面取得创新进展 化学合成和生物学，以确保迅速开发新的治疗分子。这些分子 通常由多用途的构建块构建。理想情况下，这些分子碎片应该从 容易获得和多样化的起始材料。拟议工作的长期目标有两个；第一， 让本科生有机会进行实践研究，旨在加强他们的规划， 执行和分析技能。第二，利用FGCU的设施和改善我们的研究环境 设备，以检查新的，更有效的途径，以获得宝贵的小分子通过评估新的 作为催化剂的一类异双金属络合物与它们的无配体对应物。这种方法是 创新之处在于它结合了两种过渡金属(如Pd-Ag或Pd-Cu)的力量和一种新的钳子- 就像配体使容易获得的起始材料官能化并构建不同的结构基序一样， 大量使用无害的试剂，即水和空气。这项拟议工作的基本原理是 最近通过等电点证明了异双金属催化剂的反应性(见研究战略部分)。 这项建议的第一个目标是设计、合成和充分阐明几个化合物的结构和反应活性。 异双金属络合物，以及催化剂-底物相互作用的密度泛函计算。第二个目标 就是评估我们的新络合物是否有有机配体。烷基卤化物直接转化为 在本课题组中发现的一种新的功能基团相互转化，将被用作筛选 转型。第三个目标是检查和评价所提议的双金属催化剂的催化活性。 在炔烃直接转化为烯酮的反应中，络合物与其无配体的等价物的比较。总体结果 从所有三个目标获得的结果将有助于阐明我们的新催化系统的重要机械方面和 采用这些新战略来加快天然产品的合成。预计会出现以下情况 预期结果：首先，该研究项目将为本科生提供一个培训平台 药理相关分子的催化与合成。第二，提供更方便的访问 合成用于治疗人类疾病的治疗剂所需的小分子。因此，扩展 当前的有机工具包。第三，这项工作将显著减少所需的合成步骤，同时 同时提供新的合成键断开和独特的反应性。第四，方法 所描述的方法比目前的合成方法更具成本效益和更环保 用于合成关键中间体。预计这些结果将产生重大的积极影响 面向所有参与药物发现的本科生的职业生涯。能够更高效地 组装复杂的药物靶点将有益于人类健康。

PROJECT SUMMARY The detection of new microbe strains together with drug resistant bacteria require innovative advances in chemical synthesis and biology to ensure prompt development of new therapeutic molecules. These molecules are typically built from versatile building block. Ideally, these molecular fragments should be obtained from readily available and diverse starting materials. The long-term goal of the proposed work is two-fold; first, to give undergraduate students the opportunity to perform hands-on research, aiming to enhance their planning, executing, and analysis skills. Second, to improve our research environment by utilizing FGCU facilities and equipment to examine new, more efficient routes to access valuable small molecules via assessment of a new class of heterobimetallic complexes as catalysts versus their ligandless counterparts. This approach is innovative as it combines the power of two transition metals (e.g., Pd-Ag or Pd-Cu) with a new class of pincer- like ligands to functionalize readily available starting materials and to construct diverse structural motifs, making heavy use of benign reagents, namely water and air. The rationale for this proposed work is based on the recent demonstrated reactivity of heterobimetallic catalysts by the PI (see the research strategy section). The first aim of this proposal is to design, synthesize, and fully elucidate the structure and reactivity of several heterobimetallic complexes, together with DFT calculations of catalyst-substrate interactions. The second aim is to evaluate our new complexes with or without organic ligands. The direct conversion of alkyl halides into enals/enones, a novel functional group interconversion discovered in our group, will be used as the screening transformation. The third aim will examine and evaluate the catalytic activity of the proposed heterobimetallic complexes versus their ligand-free equivalents in the direct conversion of alkynes into enones. Overall results obtained from all three aims will help elucidate important mechanistic aspects of our new catalytic systems and employment of these new strategies to the expedite synthesis of natural products. The following expected outcomes are foreseen: First, this research program will give a training platform to undergraduate students in catalysis and synthesis of pharmacological relevant molecules. Second, to provide much easier access to small molecules required to synthesize therapeutic agents used to treat human illnesses. Thus, expanding the current organic toolkit. Third, this work will reduce significantly the number of synthetic steps required, while simultaneously giving access to new synthetic bond disconnections and unique reactivity. Fourth, the approach described is both more cost efficient and more environmentally friendly than current synthetic approaches employed in synthesis of key intermediates. These outcomes are expected to have a significant positive impact towards the careers of all undergraduate students involved and drug discovery. The ability to more efficiently assemble complex pharmaceuticals targets will benefit human health.