Stereochemistry of natural products from vibrational circular dichroism

• Published in: Chemical communications (Cambridge, England) England), 2024-09, Vol.6 (76), p.1439-145
• Main Authors: Batista, Andrea N. L, Valverde, Alessandra L, Nafie, Laurence A, Batista Jr, João M
• Format: Article
• Language: English
• Subjects: Configurations; Dichroism; Metabolites; Molecular spectroscopy; Natural products; Stereochemistry
• ISSN: 1359-7345; 1364-548X; 1364-548X
• DOI: 10.1039/d4cc02481h

Secondary metabolites from land and marine (micro)organisms have been at the focus of the drug discovery process for many years. One of the reasons for this success is nature's incredible ability to create intricate molecular scaffolds. Such structural richness, however, makes the structural elucidation, and the absolute configuration assignment in particular, a challenging process. Vibrational circular dichroism (VCD) has emerged as one of the most reliable and versatile methods to unambiguously assign both the absolute configuration and conformations of chiral molecules in solution. Although VCD is no longer a curiosity in the field of molecular spectroscopy after 50 years since its first report, it is still underutilized by natural product chemists worldwide for varying reasons. Herein, we highlight the evolution of the application of VCD to natural product chemistry, focusing on its strengths as well as points that still need improvement. General guidelines for the correct application of VCD to stereochemical studies are also provided. VCD spectroscopy associated with DFT calculations is a powerful tool to unambiguously assign both the absolute configurations and conformations of chiral secondary metabolites directly in solution.