Chemical Constituents Of Baphicacanthis Cusiae Rhizoma Et Radix And Structural Identification Based On Quantum Chemical Calculations

Natural products and their derivatives are one of the important sources to discover lead compounds and new drugs.The isolation and structure identification of natural products is an important prerequisite for clarifying the structure-activity relationship and developing new chemical entities.This paper mainly focuses on the isolation and structural identification of natural products.Using a variety of separation methods,the chemical constituents of Baphicacanthis cusiae Rhizoma et Radix was studied systematically.Furthermore,quantum chemical calculation of spectroscopic data of small molecules,such as NMR,ECD and OR calculations,were used to facilitate the structure identification process.A software for simulating ECD curve of Gaussian calculation results was developed to simplify the process of ECD calculation results.The 95% ethanol extract of B.cusiae Rhizoma et Radix was purified by multichromatographic methods including microporous resin,silica gel,Sephadex LH-20,and C18 reversed-phase column chromatography.Fourteen compounds were isolated and structurally identified,including five phenylethanoid glycosides,five phenylpropanoids,one lupinane triterpene,two alkaloids,and one flavonoid.Compound 1 was a new phenylethanoid glycoside,and the other 10 compounds were isolated for the first time from B.cusiae Rhizoma et Radix except compounds 12,13,and 14.Organic small molecules,especially natural products,have complex and diverse structures,and generally contain multiple chiral centers,so determination of the absolute configuration has always been a challenge in structural elucidation.The current methods for determining the absolute configuration of chiral molecules include:chiral organic synthesis;NMR-based mosher method or shift reagent method;X-ray single crystal diffraction;chiroptical spectroscopy,etc.Among these methods,chiroptical spectroscopy is widely used because it has low requirements on purity and crystallization of samples and requires less samples for measurement.After measurement,samples can be recovered.With the rapid development of computer technology and the maturity of Density Functional Theory(DFT)and Time-Dependent Density Functional Theory(TDDFT),quantum chemical calculations have gradually replaced traditional empirical rules and become an effective and popular technique for determining the absolute configuration of natural products.In this paper,quantum chemical calculation methods applied to the relative and absolute configuration of natural products were reviewed,and the configuration problems of various natural products were studied and solved,including:(1)Three examples of NMR calculations aimed at determining relative configurations.The chemical shifts of three 9,11-seco tetracyclic triterpenoids were calculated by density functional theory.The relative configurations of the three new compounds were determined by DP4+ possibility analysis based on comparison of the calculated data and experimental data,which enables the structure of previously published euphorol J to be revised as compound 15;(2)16 examples of electronic circular dichroism(ECD)computation and simulation for the determination of absolute configurations.The ECD of 8 new compounds(five racemic alkyl-benzofuran dimers,two 9,11-seco tetracyclic triterpenes and macrocyclic supramolecular chiral compounds)was simulated by timedependent density functional theory(TDDFT);(3)5 examples of optical rotation calculation research to determin the absolute configurations.The optical rotation values of five racemic alkyl-benzofuran dimers were calculated using density functional theory,and the theoretical calculation values were compared with experimental data to assist the determination of the absolute configuration.Based on a lot of example study and literature survey,this article mainly summarizes the simulation method of ECD curve,and the evaluation standards of ECD calculation result.Furthermore,in order to improve the efficiency of data processing and plotting,a software was developed to automatically processing of Gaussian ECD calculation results and simulation of ECD curve based on Python language,which facilitated the data processing and result evaluation of the calculated ECD.