The determination of natural products stereochemistry remains a formidable task. Residual dipolar couplings (RDCs) induced by anisotropic media are a powerful tool for determination of the stereochemistry of organic molecule in solution. This review will provide a short introduction on RDCs-based methodology for the structural elucidation of natural products. Special attention is given to the current availability of alignment media in organic solvents. The applications of RDCs for structural analysis of some examples of natural products were discussed and summarized. Graphical Abstract This review provides a short introduction on RDCs-based methodology for the structural elucidation of natural products. Special attention is given to the current availability of alignment media in organic solvents. The applications of RDCs for structural analysis of some examples of natural products were discussed and summarized.

The determination of stereochemistry of organic molecules still represents one of the major obstacles in the structure elucidation procedure in drug discovery. Although the application of residual dipolar couplings (RDCs) has revolutionized this field, residual chemical shift anisotropies (RCSAs) which contain valuable structural information for nonprotonated carbons, have only been scarcely employed so far. In this study, we present a simple but highly effective solution to extract RCSAs of the analytes in a liquid crystalline phase formed by AAKLVFF oligopeptides. This method does not require any special instruments, devices or correction during post-acquisition data analysis, and thus can be easily applied in any chemistry laboratory. To illustrate the potential of this method, the relative configurations of four known natural products (1-4) belonging to different structural classes were confirmed. Moreover, we unambiguously elucidated the stereochemistry of spiroepicoccin A (5), a rare thiodiketopiperazine marine natural product whose configuration could not be assigned based on conventional NMR methods.