Biochemical Model Reactions

项目描述（申请人提供）：本项目旨在发明和研究能够模仿天然酶的新型分子。在项目的第一部分，我们将研究模仿细胞色素P-450类酶的新型催化剂。在我们的酶模拟物中，底物与催化剂结合，然后在仅由催化剂/底物复合物的几何形状决定的位置进行羟基化或环氧化。这与化学合成中的正常情况相反，在化学合成中，底物的内在反应性在决定反应发生的位置方面起着主要作用——通常它们起着唯一的作用。我们建议1)改进底物与模拟酶结合的方式，特别是使用包括金属离子配位在内的“点环”计划来结合常见的底物；2)将工作扩展到新的基材，包括那些本身具有柔性的基材；3)研制实用的氧化试剂。我们期望这种仿生合成反应可以应用于制药工业中有用的药用化合物的合成和制造。

DESCRIPTION (provided by applicant): This project is aimed at inventing and studying novel molecules that can imitate natural enzymes. In the first part of the project we will study novel catalysts that imitate the enzymes belonging to the class called cytochrome P-450. In our enzyme mimics substrates are bound to the catalyst and then hydroxylations or epoxidations are performed at sites determined only by the geometry of the catalyst/substrate complex. This is in contrast to the normal situation in chemical syntheses in which the intrinsic reactivities of the substrates play a major role in determining where reactions occur--frequently they play the only role. We propose to 1) improve the way in which substrates are bound to the enzyme mimics, in particular using a "point and ring" plan including metal ion coordination for binding commonly available substrates; 2) extend the work to novel substrates, including those that are themselves flexible; and 3) develop practical reagents for the oxidations. We expect that such biomimetic synthetic reactions could be applied to the synthesis and manufacturing of useful medicinal compounds in the pharmaceutical industry. The second part of the project deals with artificial enzymes -- enzyme mimics -- that are based on synthetic polymers, including dendrimers. Here we perform the reactions in water and take advantage of the fact that the interior of the polymer is non-aqueous, as is true in enzymes as well. Thus we obtain hydrophobic binding of substrates but very rapid reactions in the polymer interiors. We will be working with various polymers, and modifying them with hydrophobic units. We propose reactions catalyzed by enzyme mimics that have coenzymes either attached or reversibly bound, with the aim of developing biomimetic methods to synthesize amines such as amino acids as well as products from the special catalysis that thiamine and other thiazolium ions produce. We will be focusing on producing products with high enantiomeric excesses, in part by using chiral polyamines produced by the reduction of polypeptides. Here too the health relevance is the development of novel synthetic methods that could be useful in the manufacture of medicinal compounds. In addition, both parts of the project will help us understand natural enzymes.