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

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 o S 5 conformations of the β-glucose core in DMSO- d 6 to an inverted 1 C 4 conformation in methanol- d 4 , 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. Conformational preferences of corilagin in DMSO and methanol solutions have been erroneously interpreted as the existence of its α-anomer, isocorilagin.