TEMPLATE DIRECTED COMBINATORIAL SYNTHESIS

该项目的目标是设计和发现新的 用于对映选择性有机合成的催化剂体系， Diels-Alder反应的外选择性催化剂。 并行 目标是创造一种新的方法， 催化剂和组合化学的其他目标。 基于 有机分子的分子识别研究以及 抗体催化的进展，分子库将是 合成的，其被预先组织用于催化活性。 的 文库将通过添加不同的库来合成， 将其加入到负载化合物中的结构单元将是 通过与模拟过渡态的化合物结合来模板化 感兴趣 通过这种方式，最有效地 结合反应过渡态模拟物将被纳入 那些最不有效的费用。 选择性富集 潜在的催化剂将允许大的潜在的催化多样性， 要采样的成分，并将添加一定程度的选择， 扩增至合成组合文库。 化合物 将筛选所获得的结合和催化活性， 鉴定，独立合成和表征。 基于 所发现的先导结构以及动力学、化学和结构 通过对催化剂及其底物的分析，优选出的催化剂将 合成，其中纳入所获得的机械知识。

The objective of this project is the design and discovery of new catalyst systems for enantioselective organic synthesis, directed toward an exo-selective catalyst of the Diels-Alder reaction. A parallel objective is the creation of a new methodology for the generation of catalysts and other targets of combinatorial chemistry. Based on the molecular recognition studies on organic molecules as well as the advances in antibody catalysis, libraries of molecules will be synthesized which are pre-organized for catalytic activity. The libraries will be synthesized by the addition of diverse pools of building blocks whose addition to the supported compound will be templated via binding to a compound which models the transition state of interest. In this way, the building blocks which most effectively bind the reaction transition state-mimic will be incorporated at the expense of those least effective. The selective enrichment of the potential catalysts will allow a large potential diversity of catalytic compositions to be sampled, and will add a degree of selection and amplification to the synthetic combinatorial library. The compounds obtained will be screened for binding and catalytic activity, identified, and independently synthesized and characterized. Based on the lead structures discovered and the kinetic, chemical and structural analysis of the catalyst and its substrates, optimized catalysts will be synthesized which incorporate the mechanistic knowledge obtained.