Yan Jiangli, Delaglio Frank, Kaerner Andreas, Kline Allen D, Mo Huaping, Shapiro Michael J, Smitka Tim A, Stephenson Gregory A, Zartler Edward R
Discovery Chemistry Research and Technologies, Lilly Research Labs, Lilly Corporate Center, Eli Lilly & Company, Indianapolis, Indiana 46285, USA.
J Am Chem Soc. 2004 Apr 21;126(15):5008-17. doi: 10.1021/ja037605q.
Residual dipolar couplings (RDCs), in combination with molecular order matrix calculations, were used to unambiguously determine the complete relative stereochemistry of an organic compound with five stereocenters. Three simple one-dimensional experiments were utilized for the measurements of (13)C-(1)H, (13)C-(19)F, (19)F-(1)H, and (1)H-(1)H RDCs. The order matrix calculation was performed on each chiral isomer independently. The fits were evaluated by the comparison of the root-mean-square deviation (rmsd) of calculated and measured RDCs. The order tensor simulations based on two different sets of RDC data collected with phage and bicelles are consistent. The resulting stereochemical assignments of the stereocenters obtained from using only RDCs are in perfect agreement with those obtained from the single-crystal X-ray structure. Six RDCs are found to be necessary to run the simulation, and seven are the minimum to get an acceptable result for the investigated compound. It was also shown that (13)C-(1)H and (1)H-(1)H RDCs, which are the easiest to measure, are also the most important and information-rich data for the order matrix calculation. The effect of each RDC on the calculation depends on the location of the corresponding vector in the structure. The direct RDC of a stereocenter is important to the configuration determination, but the configuration of stereocenters devoid of protons can also be obtained from analysis of nearby RDCs.
残余偶极耦合（RDCs）与分子序矩阵计算相结合，被用于明确确定一种具有五个立体中心的有机化合物的完整相对立体化学结构。利用三个简单的一维实验来测量(^{13}C - ^1H)、(^{13}C - ^{19}F)、(^{19}F - ^1H)和(^1H - ^1H)的RDCs。对每个手性异构体独立进行序矩阵计算。通过比较计算得到的和测量得到的RDCs的均方根偏差（rmsd）来评估拟合情况。基于用噬菌体和双分子层收集的两组不同RDC数据进行的序张量模拟结果是一致的。仅使用RDCs得到的立体中心的立体化学归属与从单晶X射线结构得到的结果完全一致。发现运行模拟需要六个RDCs，对于所研究的化合物，七个是获得可接受结果的最小值。还表明，最容易测量的(^{13}C - ^1H)和(^1H - ^1H)的RDCs也是序矩阵计算中最重要且信息丰富的数据。每个RDC对计算的影响取决于结构中相应向量的位置。立体中心的直接RDC对构型确定很重要，但没有质子的立体中心的构型也可以通过分析附近的RDCs获得。
