Institute of Organic Chemistry and Institute for Biological Surfaces, Karlsruhe Institute of Technology, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany.
Magn Reson Chem. 2012 Dec;50 Suppl 1:S92-101. doi: 10.1002/mrc.3902.
The configurational analysis of organic compounds is an important application for high resolution NMR spectroscopy. In the present study, a tetra-substituted pyrrolidine with four chiral carbon atoms is analyzed using classical methods based on (3) J and NOE data in solution and compared and verified with recently introduced alternative approaches via residual dipolar couplings (RDCs) in two weak anisotropic alignment media. The molecule shows sufficient rigidity in the five-membered ring for the configurational characterization with the various techniques. However, the flexibility caused by the many freely rotating bonds potentially poses problems for the interpretation of data. It is shown that RDCs measured in poly-γ-benzyl-l-glutamate and a stretched polydimethylsiloxane gel provide useful information for the distinction of diastereomers, but the success varies with the data interpretation strategy used. Although a general improvement of corresponding correlation factors is observed when limiting data to a subset of dipolar couplings directly connected to the central ring, the distinction power is reduced because of the smaller number of RDCs available for potential model falsification. Singular value decomposition for fitting experimental RDCs is able to distinguish in most cases the correct from incorrect configurations, but the differences in correlation factors can be relatively small. Surprisingly, predicting RDCs using the rod model as implemented in PALES gives best results in distinguishing the eight possible diastereomers. It is also found that the use of proton-phosphorus and carbon-phosphorus RDCs helps with the configurational analysis of the model compound.
有机化合物的构象分析是高分辨率 NMR 光谱学的一个重要应用。在本研究中，使用基于溶液中（3）J 和 NOE 数据的经典方法分析了具有四个手性碳原子的四取代吡咯烷，并与最近通过在两种弱各向异性对齐介质中的残剩偶极耦合 (RDC) 引入的替代方法进行了比较和验证。该分子在五元环中具有足够的刚性，可用于各种技术的构象特征。然而，由于许多自由旋转的键，分子的灵活性可能会对数据的解释造成问题。结果表明，在聚γ-苄基-L-谷氨酸和拉伸的聚二甲基硅氧烷凝胶中测量的 RDC 为区分非对映异构体提供了有用的信息，但成功取决于所使用的数据解释策略。尽管当将数据限制为与中心环直接连接的一组偶极耦合时，相应的相关因子得到普遍提高，但由于可用的 RDC 数量减少，用于潜在模型伪造的 RDC 数量减少，因此区分能力降低。用于拟合实验 RDC 的奇异值分解在大多数情况下能够区分正确的和不正确的构型，但相关因子的差异可能相对较小。令人惊讶的是，使用 PALES 中实现的棒模型预测 RDC 可以在区分八个可能的非对映异构体方面取得最佳结果。还发现使用质子-磷和碳-磷 RDC 有助于模型化合物的构象分析。
