Geraniol-Derived Monoterpenoid Glucosides from Rhodiola rosea: Resolving Structures by QM-HifSA Methodology

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2023-02, Vol.86 (2), p.256-263
• Main Authors: Tang, Yu, Friesen, J. Brent, Lankin, David C., McAlpine, James B., Nikolić, Dejan, Chen, Shao-Nong, Pauli, Guido F.
• Format: Article
• Language: English
• Subjects: Glucosides - chemistry; Molecular Structure; Monoterpenes; Plant Extracts; Reproducibility of Results; Rhodiola - chemistry
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.2c00836

Monoterpenoids are integral to the chemical composition of the widely used adaptogenic dietary supplement Rhodiola rosea. The present study expands the chemical space and stereochemical information about these taxon-specific constituents from the isolation and characterization of five geraniol-derived glucosides, 1–5. While 1 and 2 exhibited almost identical NMR spectra and shared the same 2D structure ascribed to the 4-hydroxygeraniolglucoside previously described as rosiridin, the NMR-based Mosher ester method revealed the enantiomeric nature of their aglycone moieties. This marks the first report of enantiomeric aglycones among geraniol derivatives. These findings also resolve the long-standing dispute regarding the absolute configuration of rosiridin and congeneric C-4 hydroxylated geraniols and may help explain incongruent bioactivity reports of R. rosea extract. Moreover, the three previously undescribed geranioloids 3–5 were fully characterized by extensive spectroscopic analysis. Quantum mechanics-driven 1H iterative functionalized spin analysis (QM-HifSA) was performed for all isolates and provides detailed NMR spin parameters, with adequate decimal place precision, which enable the distinction of such close congeners exhibiting near identical NMR spectra with high specificity. The outcomes also reinforce the importance of reporting chemical shifts and coupling constants with adequate decimal place precision as a means of achieving specificity and reproducibility in structural analysis.