Structure-chiroptical properties relationship in clavams: An experimental and theoretical study
Structure-chiroptical properties relationship in clavams: An experimental and theoretical study
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DOI：
10.1002/chir.20484
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发表时间：
2008-05-15
期刊：
影响因子：
2
通讯作者：
Frelek, Jadwiga
中科院分区：
文献类型：
--
作者：
Chmielewski, Marek;Cierpucha, Maciej;Frelek, Jadwiga
众所周知，蛤蚌的生物活性很大程度上取决于环结碳原子的绝对构型。因此，发展新型苯胺类氧类似物的高效立体控制合成方法和构效关系研究需要对新合成化合物的绝对立体化学性质进行可靠的测定。最近，我们提出了一个经验螺旋规则，将桥头堡碳原子的构型与蛤蚌电子圆二色（ECD）光谱中观察到的240 nm波段的符号联系起来。在目前的工作中，我们研究了这种结构-性质关系在分子中具有额外干扰发色团的几种对映体模型化合物中的有效性。为此，结合ECD光谱和时变密度泛函理论（TD-DFT）被使用。将ECD光谱与TD-DFT计算得到的理论光谱进行比较，合理地解释了在250 ~ 220 nm光谱范围内观察到的棉花效应。此外，计算证实了本文研究体系的螺旋度规则的有效性，并表明ECD光谱可以作为蛤蚌三维分子结构的高灵敏度探针。
It is well known that the biological activity of clavams depends strongly on the absolute configuration at the ring junction carbon atom. Therefore, development of the efficient stereo-controlled synthetic methods for the new oxygen analogs of penams, and the structure-activity relationship studies call for a reliable determination of the absolute stereochemistry of newly synthesized compounds. Recently, we proposed an empirical helicity rule relating the configuration of the bridgehead carbon atom to the sign of the 240 nm band observed in the electronic circular dichroism (ECD) spectrum of clavams. In the present work, we investigate the validity of this structure-property relationship for several enantiomeric pairs of model compounds possessing an additional, interfering chromophore in the molecule. For this purpose a combination of the ECD spectroscopy and the time-dependent density functional theory (TD-DFT) is used. A comparison of the ECD spectra with the theoretical ones obtained by the TD-DFT calculations gives a reasonable interpretation of the Cotton effects observed in the 250-220 nm spectral range. Moreover, the calculations confirm validity of the helicity rule for systems studied here and demonstrate that ECD spectroscopy may be used as a highly sensitive probe of the three-dimensional molecular structure of clavams.