NMR Methods for the Unambiguous Identification of meso-Compounds and the Racemate of Their Corresponding Enantiomers

如果感兴趣的分子不能结晶，核磁共振波谱是最重要的结构表征方法。一类有规律发生的分子，在结构确定方面特别困难，是由所谓的介观化合物形成的，它很难与溶液中相应对映体的外消旋体区分开来。今天的核磁共振方法只允许在可以检测到跨越对称中心的标量耦合的情况下进行明显的识别。目前还没有适用于具有重叠多态或核磁共振活性核过少的分子的实验。此外，现有的方法只能通过信号加倍来识别中位化合物，而相应的外消旋体不能从偶然的简并光谱中区分出来。该项目的目标是开发一套广泛适用的核磁共振方法来鉴定介体/外消旋体。中心目标是通过同核和异核去耦以及通过类似tocsy的脉冲序列元素在对称中心的间接耦合自旋的相关性来获得最大的分辨率。此外，部分对准引入的剩余偶极耦合的使用也将遵循，因为它们允许远距离的相关性，并使外消旋物的积极识别成为可能。在低质子密度的化合物中，将发展溶解- dnp的快速实验，并相应提高检测低丰度原子核的灵敏度。最后，在特殊情况下，通过选择剩余四极和偶极耦合演化，寻求最大限度地区分立体中心。

NMR spectroscopy is the most important structural characterization method if a molecule of interest cannot be crystallized. A regularly occurring class of molecules with particular difficulties in structure determination is formed by so-called meso compounds, which can hardly be distinguished from the racemate of the corresponding enantiomers in solution. Todays NMR methods allow a distinct identification only in cases when a scalar coupling across the symmetry center can be detected. No applicable experiments exist so far for molecules with overlapping multiplets or with too few NMR-active nuclei. In addtion, existing methods only allow the positive identification of meso-compounds by signal doubling, while the corresponding racemate cannot be distinguished from an accidentally degenerate spectrum. The goal of this project is the development of a set of broadly applicable NMR methods for meso/racemate identification. Central aims are maximum resolution via homonuclear and heteronuclear decoupling as well as the correlation of indirectly coupled spins across the symmetry center via TOCSY-like pulse sequence elements. Also the usage of residual dipolar couplings introduced by partial alingment will be followed, because they allow correlations over large distances and make the positive identification of racemates possible. In compounds with low proton-density fast experiments will be developed for the application of dissolution-DNP and the corresponding boost in senstivity in the detection of low abundance nuclei. Finally maximum distinction of the stereogenic centers is sought by selected residual quadrupolar and dipolar coupling evolution for special cases.