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

项目摘要 新的微生物菌株和耐药细菌的检测需要在以下方面取得创新性进展： 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 通常由多功能的构建块构建。理想情况下，这些分子片段应该从 容易获得的和多样的起始材料。拟议工作的长期目标有两个方面：第一， 让本科生有机会进行实践研究，旨在提高他们的规划， 执行和分析能力。第二，利用FGCU设施改善我们的研究环境， 设备，以检查新的，更有效的途径，以获得有价值的小分子通过评估一个新的 作为催化剂的一类杂环化合物与它们的无配体对应物的比较。这种方法 其创新性在于其结合了两种过渡金属的能力（例如，Pd-Ag或Pd-Cu）与一种新的钳形- 类似于配体官能化容易获得的起始材料和构建不同的结构基序， 大量使用良性试剂，即水和空气。这项拟议工作的理由是基于 PI最近证明了杂多酸催化剂的反应性（见研究策略部分）。 本建议的第一个目标是设计，合成，并充分阐明几个结构和反应性 杂环化合物，以及催化剂-底物相互作用的DFT计算。第二个目的 是评估我们的新配合物有或没有有机配体。卤代烷直接转化为 烯醛/烯酮是本课题组发现的一种新的官能团互变， 转型第三个目标是研究和评价所提出的杂环化合物的催化活性 络合物与它们的无配体的等价物在炔直接转化成烯酮中的比较。总体结果 从所有三个目标获得的信息将有助于阐明我们新催化体系的重要机理方面， 采用这些新策略来加速天然产物的合成。下列预期 结果是预见：首先，这项研究计划将提供一个培训平台，本科生在 药理学相关分子的催化和合成。第二，提供更容易获得 合成用于治疗人类疾病的治疗剂所需的小分子。因此，扩大 当前的有机工具包第三，这项工作将大大减少所需合成步骤的数量， 同时获得新的合成键断开和独特的反应性。第四，方法 所描述的是比目前的合成方法更成本有效和更环境友好的方法 用于关键中间体的合成。预计这些成果将产生重大的积极影响 对所有参与的本科生的职业生涯和药物发现。能够更有效地 组装复杂的药物靶标将有益于人类健康。

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.