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

核磁共振波谱是一种强有力的工具，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。关于溶液中的三维结构的信息又可以与活性和/或选择性相关联。这也适用于催化，只要与催化循环相关的化合物或中间体可以在尽可能接近现实的条件下进行分析。此外，NMR光谱允许通过一系列技术研究分子间的相互作用。这些主要是基于从“配体”到“粘合剂”的磁化转移，反之亦然。在药物发现中，这些技术用于搜索与药物相关的线索。“结合剂”通常是靶生物大分子（例如蛋白质）。本文提出用核磁共振波谱方法进一步研究氢键和伦敦色散相互作用在一系列肽催化剂拆分反式-1，2-环烷烃二醇中的重要性。Thiele和Schreiner小组先前表明，对于该特定系统，可以通过NMR光谱观察到催化剂和底物之间的分子间相互作用。在本项目中，应调查特殊选择性的原因。应采用不同的NMR光谱技术，在一系列二醇（表现出不同的选择性和分散相互作用表面，但具有相同的氢键结合能力，相对于相同的分散相互作用表面和不同的氢键结合能力）上，通过NMR光谱追踪氢键对分散相互作用的单独贡献。此外，应研究具有增加的氨基酸极化率的不同肽催化剂，其主要提供相互作用表面（所谓的分散能量供体氨基酸）。然后将设想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Dakin-West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.