The Application Of Quantum Chemistry In Determining The Absolute Configuration In The Study Of Natural Chiral Product

In the research of natural products, it is difficult to determine the absolute configuration of natural chiral compounds. Currently, the dominating methods to determine the absolute configuration include X-ray diffraction, rotary dispersion, derivate of the structure and so on. However, there are some limitations in these methods, for instance, X-ray diffraction is not suitable to determine the absolute configuration of product with insufficient content to crystallize; furthermore, the complex structures of natural products result in the difficulties in the derivatization of the structure; while the rotary dispersion and circular dichroism need the quantitative value of similar structure reported in the reference. With the development of quantum chemistry theory, calculating ECD spectra and then comparing with the experimental value has developed as a supplement to the traditional methods of determining the absolute configuration. This method is reliable for structures which contain chromophores and have obvious Cotton effect in CD between200-400nm. In this work, we determinated the absolute configuration of five new natural chiral compounds by calculating their ECDs and comparing the computational results with the experimental results.In the first part, we calculated the ECDs spectra of four bioactive jatropholane-type diterpenes, named as sikkimenoids A-D(1-4), which are extracted from Euphorbia sikkimensis and characterized by a5/6/7/3fused ring system, a structurally unique and rare chemotype. Only three examples of this type are known. The absolute configuration of the jatropholane core has remained a challenge due to the lack of appropriate functional groups for chemical derivatization and the quantity limitation of samples. Based on their relative configuration, their absolute configurations were established by ECD spectra. Finally, we get the conclusion that the absolute configuration of this four compounds is5S,9S,11S,13S. Furthermore, we have explained the Cotton effect by analyzing the calculated molecular orbital.In the second part, we analyzed a diterpenoid compound, named as Merrilliadione (5), which was separated from illicium merrillianum. The absolute configuration of this compound can’t be determined because of the difficulties in crystallizing, even though the relative configuration of this compound was elucidated by analysis of R.OESY spectrum. Compared to compound1-4, compound5was more flexible with a longer side chain. Based on the result of conformational analysis, we calculated the major conformational ECDs. Using Boltzmann distribution ratio and its weighted superposition, the theoretic ECDs of compound5were obtained. By comparing with the experimental value, we ultimately determined that the absolute configuration of compound5is4S,10R.