Several Study Cases Of Computational Chemistry For Configuration Determination Of Natural Products

Natural products with novel structures and extensive biological activities,which made great contributions to human health since ancient times,are a gift from nature.However,the absolute configuration identification of natural products having many types and complex constructs has always plagued natural product researchers.For a long time,the methods of identifying the absolute configuration of natural products mainly include chemical synthesis,X-ray single crystal diffraction,Mosher method and Chiral spectroscopy methods(e.g.ECD,VCD)etc.The first three of them can partly solve the configuration assignment problem,whereas,these methods either have high requirements on the amount of compounds and researchers' skills,or need high-quality single crystals,or have certain requirements on intramolecular groups,etc.These conditions limit the scope of application of traditional methods.Chiral spectroscopy is widely used because of its wide range of applications,low requirements on sample properties,and no loss during testing.However,problems such as reliance on empirical rules too much and lack of result judgment standards severely limit the development of this method.In the past ten years,computational chemistry methods based on quantum mechanics as the main theoretical foundation have largely overcome the shortcomings of the above methods,greatly enriching the means for identifying the absolute configuration of natural products,and owing to the rapid development of computer Vcomputing power and related quantum mechanics software,has made this method quickly popularized and widely used,becoming one of the most important methods in the identification of absolute configuration of natural products.In this paper,the method of applying computational chemistry to assign the relative configuration and absolute configuration of natural products is first reviewed.And then introduced in the form of research examples in different chapters.1)Two examples of NMR calculation to determine the relative configuration.Using density functional theory to calculate the chemical shifts of each atom of a novel Lycopodium alkaloid and a novel benzofurans.The relative configuration of the two compounds were determined by DP4+ possibility analysis of the calculated data and experimental data;2)14examples of ECD calculation to determine the absolute configuration.Focusing on the description of five new compounds(two Lycopodium alkaloid,two Euphorbia diterpenoids and a highly modified ingenane diterpenoid)using time-dependent density functional method.3)2 examples of OR calculation to determine the absolute configuration.Calculating two novel cucurbitane triterpenoids' OR value using time-dependent density functional method,comparing the theoretical value with the experimental data,the absolute configuration of these two compounds is determined.4)Using conformational analyses and reduced density gradient method in combination with NMR investigate the intramolecular hydrogen bonds to determine the absolute configuration.Visually investigate the intramolecular noncovalent Interactions of undescribed cycloartane triterpenoids,confirming the formation of intramolecular hydrogen bonds and the absolute configuration of the compound.In addition,suggestions are given for the selection of functionals and basis sets for each calculation task.Through a total of 19 calculation examples,the application of quantum chemical calculation methods in the configuration assignmemnt of natural products is systematically described.The operation process of the entire calculation and theselection of theoretical methods are briefly summarized in the article,which make contribution to the further promotion of this method.