NMR-spectroscopic investigations towards the reasons for selectivity in peptide catalysis

核磁共振波谱是以原子分辨率获得有机、有机金属、无机或生物分子化合物在溶液中的结构和动力学信息的有力工具。有关溶液中三维结构的信息又可以与活性和/或选择性联系在一起。如果与催化循环相关的化合物或中间体能够在尽可能接近实际的条件下进行分析，催化也是如此。此外，核磁共振波谱允许通过一系列技术来研究分子间的相互作用。这主要是基于从‘配体’到‘粘合剂’的磁化转移，反之亦然。在药物发现中，这些技术被用来寻找与药物相关的线索。粘合剂通常是目标生物大分子(例如蛋白质)。在催化方面，配体可以是催化剂和底物。本文建议使用核磁共振波谱方法进一步研究氢键和伦敦分散相互作用在一系列多肽催化剂(S)催化下拆分反-1，2-环烷二醇的重要性(S)。Thiele和Schreiner基团先前表明，对于这个特殊的体系，可以通过核磁共振光谱观察到催化剂和底物之间的分子间相互作用。在本项目范围内，应调查异常选择性的原因。氢键对分散相互作用的单独贡献应在一系列二元醇上使用不同的核磁共振波谱技术(表现出不同的选择性和分散相互作用表面，但氢键能力与相同的分散相互作用表面和不同的氢键能力相比)跟踪到核磁共振波谱。此外，还应研究不同的多肽催化剂，提高氨基酸的极化率，主要提供相互作用表面(即所谓的色散供能氨基酸)。然后应设想将本文使用和开发的方法应用于其他(肽)催化的反应，例如对映选择性的达金-韦斯特反应。

NMR spectroscopy is a powerful tool to obtain information on the structure and dynamics of organic, organometallic, inorganic or biomolecular compounds in solution at atomic resolution. Information about the three dimensional structure in solution can in turn be linked to activity and/or selectivity. This can also be true for catalysis, provided compounds or intermediates relevant for the catalytic cycle can be subjected to analysis at conditions as close to reality as possible. Furthermore, NMR spectroscopy allows the investigation of intermolecular interactions via a series of techniques. These are mostly based on magnetisation transfer from a ‘ligand’ to a ‘binder’ or vice versa. In drug discovery these techniques are used to search for pharmacologically relevant leads. The ‘binder’ usually is the target biomacromolecule (protein, e.g.) and the ‘ligand’ a proposed drug; in terms of catalysis this could be the catalyst and the substrate.It is proposed here to use NMR-spectroscopic methods to (further) investigate the importance of hydrogen bonds and London dispersion interactions in the kinetic resolution of trans-1,2-cycloalkane diols by a (series of) peptide catalyst(s). The Thiele and Schreiner groups showed previously that intermolecular interactions can be observed NMR-spectroscopically between catalyst and substrate for this particular system. Within this project the reasons for the extraordinary selectivity shall be investigated. The individual contributions of hydrogen bonds vs. dispersion interactions shall be tracked down NMR-spectroscopically employing different NMR spectroscopic techniques on a series of diols (exhibiting different selectivities and dispersion interaction surfaces but the same hydrogen bonding ability vs. the same dispersion interactions surfaces and different hydrogen bonding abilities). Additionally, different peptide catalysts with increasing polarizabilities of the amino acid, which mainly provides the interaction surface (so called Dispersion Energy Donating Amino Acids) shall be investigated. Applications of the methods used and developed herein to other (peptide) catalysed reactions - the enantioselective Dakin-West reaction, e.g. – shall then be envisioned.