New Methods for Measuring Heteronuclear Long Range Coupling Constants and Proton-Proton Coupling Constants

本文介绍了两种新的NMR技术，即高分辨HMBC（HR-HMBC）和BIRD-J分辨HMBC。1）高分辨HMBC（HR-HMBC）在传统的HMBC谱中，交叉峰包含了长程J_2<CH>分裂和/或J_<HH>2分裂的信息。由于在F_2或F_1维上的分辨率很差，很难<CH>直接从HMBC交叉峰上测量长程J_2耦合，为了解决这个问题，我们将J标度方法引入HMBC中，发展了一种新的技术HR-HMBC，在HMBC的自旋演化周期后引入J标度脉冲（--nt_1/2-180（H，C）--nt_1/2--）。在该脉冲序列中，化学位移磁化强度、J_（1-x）<HH>和J_（1-x）<CH>耦合常数分别随t_1、（n+1）t_1和nt_1的变化而变化。结果表明，J_（n=20 ~ 30）的自旋耦合常数放大了n倍<CH>，J_<HH>（n=20 ~ 30）的自旋耦合常数放大了n+1倍，从而可以方便地确定长程J_<CH>co ...更多信息 这对复杂化合物的构象分析具有重要意义。该方法具有操作简单、灵敏度高、通用性强等优点。2）BIRD-J分辨HMBC对于NMR研究有机分子的立体化学来说，质子-质子自旋耦合常数的分析是非常重要的。天然产物如聚酮化合物通常含有含仲甲基（-CH_A-CH_B（CH_3）-CH_C-）的自旋体系。在这样一个自旋系统中，质子H_B发生了复杂的分裂.因此，从H_B的多重态信号中获得自旋耦合常数变得非常困难。H_B的自旋偶联模式的分析有时是立体化学研究中必不可少的。新的核磁共振技术BIRD-J分辨HMBC和BIRD-HR-HMBC可用于克服这一问题<CH>。将标度脉冲引入HMBC中，使F_1维质子-质子自旋分裂放大n倍（n=20 ~ 30），从而使J_1的测量变得非常<CH>容易。在这些脉冲序列中，180个脉冲被放入BIRD脉冲中，BIRD脉冲只调制直接连接到^ C的质子<12>，而不调制连接到^ C的质子<13>。换句话说，直接连接到^ C的质子<13>被去耦。例如，在自旋系统（-CH_A-CH_B（^<13>CH_3）-CH_C-）中，质子H_B及其相邻的甲基质子在J分辨HMBC和HR-HMBC谱中只与H_A和H_C耦合。因此，这种技术使具有复杂分裂模式的多重态H_B的分析变得容易。该方法的应用模型化合物波特米星解释。少

We present two new NMR techniques prepared by modification of HMBC, High Resolution HMBC (HR-HMBC) and BIRD-J resolved HMBC.1)High Resolution HMBC (HR-HMBC)In the conventional HMBC spectra, the cross peaks contain information on the long-range J_<CH> splittings and/or J_<HH> splittings. Due to the poor resolution in the F_2 or F_1 dimension, however, it is difficult to measure the long-range J_<CH> couplings directly from HMBC cross peaks.In order to solve this problem, we have incorporated the J-scaling method into HMBC and developed a new technique, HR-HMBC.The J-scaling pulse (--nt_1/2-180(H,C)-nt_1/2--) is introduced after the spin evolution period of HMBC. In this pulse sequence, the magnetizations of chemical shift, J_<HH> and J_<CH> coupling constants evolve with t_1, (n+1)t_1 and nt_1, respectively. As a result, the spin coupling constants are amplified by a factor of n for J_<CH> and n+1 for J_<HH> (n=20 to 30).This modification enables to determine easily long range J_<CH> co … More uplings of complicated compounds and will be useful for conformational analysis of non-cyclic systems. Advantages of this method are simple operation, high sensitivity and general applicability.2)BIRD-J-resolved HMBCFor stereochemical studies of organic molecules by NMR, it is important to analyze proton-proton spin coupling constants. Natural products such as polyketide often contain the spin system which includes a secondary methyl group (-CH_A-CH_B(CH_3)-CH_C-). In such a spin system, proton H_B splits complicatedly. Thus, it becomes very difficult to obtain spin coupling constants from the multiplet signal of H_B. Analysis of spin coupling pattern of H_B is sometimes essential for stereochemical studies. The new NMR techniques BIRD-J-resolved HMBC and BIRD-HR-HMBC are useful in order to overcome this problem.We have already reported J-resolved HMBC^<1)> methods to observe long range J_<CH> couplings. By incorporation of the scaling pulse into HMBC, proton-proton spin splittings in the F_1 dimension are magnified by a factor of n (n=20 to 30) making measurement of J_<CH> very easy. In these pulse sequences, 180 pulse is put into BIRD pulse.The BIRD pulse modulates only protons directly connected to ^<12>C and not protons connected to ^<13>C. In other words, protons connected directly to ^<13>C are decoupled. For example, in a spin system (-CH_A-CH_B(^<13>CH_3)-CH_C-), proton H_B with its adjacent methyl protons being decoupled are coupled only to H_A and H_C in J-resolved HMBC and HR-HMBC spectra. Thus this technique enables easier analysis of the multiplet H_B with complicated splitting pattern. An application of this method to a model compound portmicin is explained. Less