1H NMR Analyses, Shielding Mechanisms, Coupling Constants, and Conformations in Steroids Bearing Halogen, Hydroxy, Oxo Groups, and Double Bonds.
1H NMR Analyses, Shielding Mechanisms, Coupling Constants, and Conformations in Steroids Bearing Halogen, Hydroxy, Oxo Groups, and Double Bonds.
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含有卤素、羟基、氧代基团和双键的类固醇的 1H NMR 分析、屏蔽机制、耦合常数和构象。
DOI：
10.1002/chin.198612053
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
U. Siehl
中科院分区：
文献类型：
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作者：
H. Schneider;U. Buchheit;N. Becker;G. Schmidt;U. Siehl
16个5 ~* H-雄甾烷和一个孕酮类似物的~ 1H NMR分析提供了甾体基本骨架的位移和偶合常数，以及氧代、羟基、卤素基团和5个双键的取代基诱导位移（SIS）。它示出了如何一个单一的2D实验补充的NOE差谱可以导致完整的分配，即使与themost复杂的自旋系统，包括，例如，29强耦合质子仅1 ppm内;从2Dtechniques的信息的准确性进行评估比较，一些ID和计算机模拟的光谱。在多达六个同时可观察到的耦合的基础上，使用一种特殊的方法来扫描特别灵活的零件的构象空间。半椅和扭曲之间的中间构象得到的扭转C14-C15-C16-07角为s 20'的D环与sp2（17-氧代）碳和s 10的sp3碳原子;观察到的平坦的配置文件，然而，也允许不同的构象的mixtures，这是由MM 2计算支持。对于4-3-A环，与半椅几何形状相比，沙发构象是有利的。所观察到的屏蔽效应的杂取代基是部分的差异与少数早期的观察，这主要是基于多取代的化合物。经典的屏蔽机制进行了评估与程序的转变，力场最小化结构的基础上。空间诱导屏蔽占主导地位的碳氢化合物，导致高场位移增加的1，3-二轴相互作用的数量。线性电场效应预测，例如，赤道和轴向质子邻近的C-Hal债券和去屏蔽观察到的双轴C-Hal/CH键安排之间的屏蔽差异。各向异性和电场效应的组合解释了在酮中观察到的所有位移，除了邻近C= 0的质子;多元线性回归分析导致Ax！C= 0=-36（-27）和2= 0=-24（-21）（10™ 3cm 3/分子，括号中为旧的ApSimon值）;然而，证明了仅基于NMR位移的分析导致宽范围的参数。平行之间 * H和13 C NMR位移绘制，特别是在y和t？有几个方面使得类固醇对于现代NMR方法的应用是特别有吸引力的挑战：（i）这些可能是最复杂的自旋系统要克服的技术问题;（ii）关于化学位移、耦合常数和分子结构之间的关系的大量未被发现的丰富信息;（iii）生物活性随结构变化的变化。高磁场，计算机辅助PFT，特别是2D NMR光谱的组合已经被几个工作者用于类固醇的分配，其中官能团和双键的存在导致光谱简化。1，2试图找到最经济的方法与这些技术，我们分析了17类固醇，包括基本骨架雄甾烷，其中包括29个不等和强耦合质子的范围内只有1 ppm.光谱技术的惊人进步使化学家们对许多新获得的数据的智能化消化感到相当惊讶。在Zürcher，3 ApSimon，4及其同事的经典研究之后，NMR shieldingparameters的定量分析几乎没有进展，他们被迫将自己主要限制在类固醇中的几个时间平均甲基信号的观察上。一个非常有用的数字
The* H NMR analyses of 16 5<* H-androstanes and one progesterone analogue furnish shifts and coupling constants for thebasic steroid skeleton and substituent-induced shifts (SIS) for oxo, hydroxy, and halogen groups as well as for a 5 double bond. It is shown how a single 2D experiment complemented by a NOE difference spectrum can lead to complete assignments even with themost complicated spin systems comprising, eg, 29 strongly coupled protons within only 1 ppm; the accuracy of information from 2Dtechniques is evaluated by comparison to some ID and computer-simulated spectra. On the basis of up to six simultaneously observable couplings, a special approach is used to scan the conformational space of particularly flexible parts. Intermediate conformations between half-chair and twist are obtained with a torsional C14-C15-C16-07 angle of s 20’for the D ring with a sp2 (17-oxo) carbon and of s 10 with only sp3 carbon atoms; the observed fiat profiles, however, allow also for mixturesof different conformations, which is supported by MM2 calculations. For the 4-3-A ring, a sofa conformation is favored compared to a half-chair geometry. Theobserved shielding effects of heterosubstituents are partially at variance with the few earlier observations, which were mostly based on polysubstituted compounds. Classical shielding mechanisms were evaluated with the program shift, based on force-field-minimized structures. Steric-induced shielding dominates in the hydrocarbon, leading to upfield shifts increasing with the number of 1, 3-diaxial interactions. Linear electric-field effects predict, eg, the shielding difference between equatorial and axial protons vicinal to C-Hal bonds and the deshielding observed for diaxial C-Hal/CH bond arrangements. A combination of anisotropy and electric-field effects explains all shifts observed in the ketones with the exception of protons vicinal to C= 0; a multilinear regression analysis leads to Ax! C= 0=-36 (-27) and 2= 0=-24 (-21)(10™ 3 cm3/molecule, old ApSimon values in parentheses); it is, however, demonstrated, that an analysis on the basis of NMR shifts alone leads to broad ranges of parameters. Parallels between* H and 13C NMR shifts are drawn, particularly at y and t? positions to C-Hal bonds.Several aspects make steroids a particularly attractive challenge for the application of modern NMR methods:(i) the technical problems to be surmounted with these probably most complicated spin systems;(ii) the largely undiscovered wealth of information regarding the relation between chemical shifts, coupling constants, and molecular structure;(iii) the change of biological activity with structural variation. The combination of high magnetic fields, computer-aided PFT, and in particular 2D NMR spectroscopy has already been used by several workers for the assignments of steroids, in which the presence of functionalities and double bonds has led to spectral simplification. 1, 2 Trying to find themost economical approach with these techniques, we analyzed 17 steroids including the basic skeleton androstane, which comprises 29 nonequivalent and strongly coupled protons over a range of only 1 ppm. The spectacular progress of spectral techniques finds the chemists rather unpreparedfor the intelligent digestion of the many newly accessible data. There has been very little progress in the quantitative analysis of NMR shieldingparameters after the classical studies of Zürcher, 3 ApSimon, 4 and co-workers, who were forced to limit themselves largely to the observation of few time-averaged methyl signals in steroids. A very useful number