HETEROCYCLE METAL PI COMPLEXES IN ORGANIC SYNTHESIS

对映体特异性构建的新策略和一般策略 具有药用价值的分子（抗病毒药、抗生素、抗肿瘤药 代理等）对NIH的整体使命是重要的。 本提案中描述的是设计和开发 容易制备的对映体纯的钼π-络合物， 不饱和氧和氮杂- 环（2 H-吡喃，1，2-二氢吡啶等），其中丰富的 各种取代基可以顺序且容易地连接在一起 区域和立体控制的方式。 附着后拆除 多个取代基将提供对映体纯的、取代的 氧和氮杂环。 原则上，这些π络合物 作为对映体纯的支架，用于快速组装 具有已知或潜在药用价值的取代杂环系统。 因此，成功实现这一新战略将 合成重要杂环化合物的新方法 具有广泛生物活性的有机化合物， 各种检测（抗病毒、抗生素等）。 此外，在本授权的范围内，金属结合配体将是 连接到聚合物基质和对映体纯的配体上 将连接氧和氮杂环支架。 协议 对于这些聚合物结合的官能化和去金属化， 将探索对映体纯的杂环支架。 这 “对映体纯支架”策略，如果充分开发 潜力，可以为快速的结构-活性- 对映体纯的取代氧与 氮杂环系统，使用组合机器人技术。

New and general strategies for the enantiospecific construction of molecules of medicinal interest (antivirals, antibiotics, antitumor agents, etc ) are important to the overall mission of the NIH. Described within this proposal are the design and development of easily-prepared, enantiomerically-pure molybdenum pi-complexes of unsaturated oxygen and nitrogen hetero- cycles (2H-pyran, 1,2-dihydropyridine, and others) to which a rich variety of substituents can be sequentially and easily attached in a regio-and stereocontrolled fashion. Demetallation after attachment of multiple substituents would provide enantiomerically-pure, substituted oxygen and nitrogen heterocycles. In principle, these pi-complexes function as enantiomerically-pure scaffolds for the rapid assembly of substituted heterocyclic systems of known or potential medicinal value. Therefore, successful achievement of this new strategy would introduce a novel method for the synthesis of important classes of heterocyclic organic compounds with demonstrated biological activity in a wide variety of assays (antiviral, antibiotic, etc). Also, within the context of this grant, a metal binding ligand will be attached to a polymer matrix and to that ligand enantiomerically-pure oxygen and nitrogen heterocyclic scaffolds will be attached. Protocols for the functionalization and demetallation of these polymer-bound enantiomerically-pure heterocyclic scaffolds will be explored. This 'enantiomerically-pure scaffold' strategy, if developed to its fullest potential, could hold great promise for rapid structure-activity- relationship studies of enantiomerically-pure substituted oxygen-and nitrogen heterocyclic systems using combinatorial robotics techniques.