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 (−)-(2R,3R)-licarin-A and (−)-(2R,3R)-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.