Determination of absolute configuration (AC) is one of the most challenging features in the structure elucidation of chiral natural products, especially those with complex structures. With revolutionary advancements in the area of quantum chemical calculations of chiroptical spectroscopy over the past decade, the time dependent density functional theory (TDDFT) calculation of electronic circular dichroism (ECD) spectra has emerged as a very promising tool. The principle is simply based on the comparison of the calculated and experimental ECD spectra: the more closely they match, the more reliable conclusion for the AC assignment can be drawn. This review attempts to use several examples representing monomeric flavonoids, rotationally restricted biflavonoids, complex hexahydroxydiphenoyl-containing flavonoids, conformationally flexible and restrained sesquiterpenoids, cembrane-africanene terpenoids, dihydropyranocoumarins, alkaloids, and dihydroxanthones to illustrate the applicability of this approach in determining the AC of structurally diverse natural products. The findings clearly indicate that the TDDFT calculation of ECD spectra can quantify the contribution of individual conformers and the interaction of multiple chromophores, making it possible to determine the AC of complex chiral molecules. The calculated electronic transitions and molecular orbitals provide new insight into the interpretation of ECD spectra at the molecular level.

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确定天然产物的绝对构型：作为工具的电子圆二色性的理论计算

绝对构型（AC）的确定是手性天然产物结构解析中最具挑战性的特征之一，尤其是那些具有复杂结构的产物。在过去十年中，随着手性光谱量子化学计算领域的革命性进步，电子圆二色性 (ECD) 光谱的时间相关密度泛函理论 (TDDFT) 计算已成为一种非常有前途的工具。原理只是基于计算和实验 ECD 光谱的比较：它们匹配得越接近，AC 分配的结论就越可靠。本综述尝试使用几个代表单体类黄酮、旋转受限双黄酮、复合六羟基二苯甲酰类黄酮的例子，构象灵活和受限制的倍半萜类化合物、Cembrane-africanene 萜类化合物、二氢吡喃香豆素、生物碱和二氢氧杂蒽酮，以说明这种方法在确定结构多样的天然产物的 AC 中的适用性。研究结果清楚地表明，ECD 光谱的 TDDFT 计算可以量化单个构象异构体的贡献和多个发色团的相互作用，从而可以确定复杂手性分子的 AC。计算出的电子跃迁和分子轨道为在分子水平上解释 ECD 光谱提供了新的见解。和二氢氧杂蒽酮来说明这种方法在确定结构多样的天然产物的 AC 中的适用性。研究结果清楚地表明，ECD 光谱的 TDDFT 计算可以量化单个构象异构体的贡献和多个发色团的相互作用，从而可以确定复杂手性分子的 AC。计算出的电子跃迁和分子轨道为在分子水平上解释 ECD 光谱提供了新的见解。和二氢氧杂蒽酮来说明这种方法在确定结构多样的天然产物的 AC 中的适用性。研究结果清楚地表明，ECD 光谱的 TDDFT 计算可以量化单个构象异构体的贡献和多个发色团的相互作用，从而可以确定复杂手性分子的 AC。计算出的电子跃迁和分子轨道为在分子水平上解释 ECD 光谱提供了新的见解。