Solution-state conformations of natural products from chiroptical spectroscopy: the case of isocorilagin

Abstract

Isocorilagin, the α-anomer of the ellagitannin corilagin, has been frequently reported in the literature as a constituent of various plant species. Its identification is based mainly on the smaller value for the coupling constant of its anomeric proton when compared to that of corilagin. A careful investigation of the corilagin structure in both methanol and DMSO solutions using NMR, electronic and vibrational CD, and DFT and MD calculations confirmed that isocorilagin is the result of a solvent-induced conformational transition of corilagin, rather than its diastereoisomer. Corilagin changes from B_1,4 and ^oS₅ conformations of the β-glucose core in DMSO-d₆ to an inverted ¹C₄ conformation in methanol-d₄, which accounts for NMR observables attributed to the alleged α-anomer. This misassignment reinforces the risks of relying upon a single technique for structural elucidation and stereochemical analysis of complex natural products, especially those containing saccharide moieties.