Confirming the Absolute Configuration of (−)-Licarin-A and (−)-Licarin-B by Vibrational Circular Dichroism and X-ray Crystallography

Plants biosynthesize complex asymmetric molecules that often contain various chiral centers in their structure, making the determination of their absolute configuration an important topic. Within the Aristolochia genus, licarins such as licarin-A and licarin-B have been isolated, and their chemical structures are well known. However, ambiguities persist regarding their absolute stereochemical assignments, which in most cases are reported solely based on the optical rotation and comparison with previous reports. In the present work, the absolute configurations of the neolignans (−)-(2 R,3 R )-licarin-A and (−)-(2 R,3 R )-licarin-B, isolated from Aristolochia glossa Pfeifer, were determined by X-ray diffraction analysis and vibrational circular dichroism (VCD) spectroscopy, employing density functional theory (DFT) calculations at the B3LYP/DGDZVP level of theory for the construction of the theoretical VCD spectra. Furthermore, the enantiomeric purity of both molecules was confirmed to be 100% by using the Flack parameter. Based on these results and the maximum optical rotation values obtained, this study provides solid and definitive evidence for the stereochemical assignment of licarins A and B, which should be considered in future reports. These structures are widely employed in synthetic and medicinal chemistry, where identifying the biologically active compound correlated to the correct stereoisomer is essential.