Selective Peptide-Based Oxidation Catalysts for Bioactive Molecule Synthesis

用于生物活性分子合成的选择性肽基氧化催化剂

基本信息

批准号：
8585860
负责人：
Scott J Miller
金额：
$ 29.61万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-12-01 至 2015-02-09
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): We wish to develop a new paradigm for the selective oxidation of complex molecules. Our approach is based on the unified development of the now-validated approach of "aspartic acid catalysis." More generally, we have documented previously unknown catalytic cycles for olefin epoxidation and the Baeyer-Villiger oxidation, wherein a carboxylic acid functions as a catalytic moiety. We are particularly eager to explore this unique catalytic strategy for these two venerable processes, which engage an intermediate peracid moiety for mechanistically distinct functions: in epoxidation, the peracid functions as an electrophile; in the Baeyer-Villiger oxidation, the peracid functions as a nucleophile. Our specific goals include development of ever-more active and selective catalysts for each process. We intend to push the frontiers for epoxidations wherein venerable catalysts fail, including applications to problems in remote, isolated olefin functionalization. We will also explore selective epoxidations of highly substituted, electron-rich arenes, such as indoles, that are relevant to natural product synthesis. We will expand the catalysts' diversity through the synthesis of libraries that will be applied to the regioselective epoxidation of polyene-containing natural products. These same catalysts will also be applied to enantioselective Baeyer-Villiger oxidations, a class of catalytic reactions that are truly under- developed from the standpoint of enantioselective catalysis. These studies will also lead to explorations of site-selective Baeyer-Villiger oxidations performed on natural products containing multiple carbonyl sites. All the while, this work will be conducted in an environment where mechanistic studies will be performed to enhance our understanding of the selective reactions we discover. So too, collaborations are in place so that the impact of our studies will expand beyond our own laboratory, assisting colleagues engaged in complex molecule total synthesis, and in the biological evaluation of the new natural product analogs we obtain.

描述（由申请人提供）：我们希望开发一个新的范式，用于选择性分子的选择性氧化。我们的方法基于“天冬氨酸催化”现已验证的方法的统一发展。更普遍地，我们已经记录了以前未知的催化周期用于烯烃环氧化和Baeyer-Villiger氧化，其中羧酸起作用作为催化部分。我们尤其渴望探索这两个古老的过程的这种独特的催化策略，这些过程与机械上不同功能的中间peracid部分作用：在环氧化中，peracid的作用为电力;在Baeyer-Villiger氧化中，Peracid起作用为亲核试剂。我们的具体目标包括为每个过程开发越来越多的活性和选择性催化剂。我们打算推动边缘的环氧化催化剂失败，包括应用于远程，孤立的烯烃功能化的问题。我们还将探索与自然产物合成有关的高度取代，富含电子富含电子领域的选择性环氧化。我们将通过合成库的多样性来扩展催化剂的多样性，这些文库将应用于含聚乙烯的天然产物的区域性环氧化。这些相同的催化剂也将应用于对映选择性的Baeyer-Villiger氧化，这是一类从对映选择性催化的角度来看，这些反应确实不足以产生。这些研究还将导致对含有多个羰基位点的天然产物进行的现场选择性的贝耶尔 - 维格利氧化作用的探索。一直以来，这项工作将在将进行机械研究的环境中进行，以增强我们对发现的选择性反应的理解。同样，合作也存在，以便我们的研究的影响将扩展到我们自己的实验室之外，从而有助于从事复杂分子总合成的同事，并对我们获得的新自然产品类似物进行生物学评估。