Progression of Absolute Configuration Determination in Natural Product Chemistry Using Optical Rotation (Dispersion), Matrix Determinant and Electronic Circular Dichroism Methods

Sheng-Ding      Zhao; Lan      Shen; Du-Qiang      Luo; Hua-Jie      Zhu

doi:10.2174/138527211795656688

Abstract

With the development of separation materials, more and more complex natural products with poly-stereogenic centers are obtained. However, due to small quantity of the isolated compounds, or no crystal formed, or complex 2D NMR correlation signals, absolute configuration identification for these compounds becomes difficult. Now, computational methods provide researchers many benefits in structural determinations for chiral natural products. Computational methods include (1) optical rotation (OR) and its dispersion (ORD) computations; (2) electronic circular dichroism (ECD or CD) calculations; (3) computations of determinant of matrix for stereogenic centers. In methods (1) to (2), the mostly used quantum theory contained density functional theory (DFT) with different basis sets, e.g. B3LYP/aug-cc-pVDZ//B3LYP/6-31G(d). Effects from solvents on OR value can be investigated using different corresponding software. In the cases, optimizations performed in the corresponding solution are helpful to obtain the correct predictions although it is not usual at present time. Matrix model as one of the mathematic methods is different from quantum methods, which is of easily being understood and effective in absolute configuration assignment for acyclic chiral compounds. In this review, necessary theory basis for the three methods are simply introduced for modern readers, the focus of which is the application of these methods in natural product chemistry by various examples reported in different journals from 1998 to the end of April of 2010 except for matrix method to the May of 2010 based on an experimental chemist's viewpoints.

Keywords: DFT, ECD, OR, absolute configuration determination, ORD COMPUTATIONS, 2D NMR methods, ROESY experiments, electronic circular dichroism ECD or CD) calculations, 13C NMR methods, Hatree-Fock (HF) calculations, density-function theory (DFT), coupled-cluster (CC) calculation, coupled-cluster single doubles (CCSD), Quantum-mechanical theory, anti-HIV-1 activity