Anisotropic NMR as a Crucial Tool for Differentiation of Epimers With High Conformational Flexibility.

Identifying the correct structures of epimers is highly challenging due to the sometimes very subtle differences in their respective NMR signatures. In this context, the analysis of carbon residual chemical shift anisotropies (13C-RCSAs) and residual dipolar couplings (RDCs) was essential for distinguishing the relative configurations of two tetraprenyltoluquinol epimeric meroterpenoids at C3 (1a and 1b). These compounds feature two remotely located stereoclusters and exhibit significant conformational flexibility. DP4-based approaches (DP4+ or J-DP4) failed to differentiate these epimers. A geometric exploration strategy was developed to investigate the conformational diversity of 1a and 1b while accounting for their inherent flexibility. Then, refining the conformational space and optimizing the fitting of the anisotropic parameters of 1a/1b measured in a 3 mm semi-micro compression device using poly-HEMA gels in DMSO enabled us to discriminate the relative configuration of them.