Quantum Mechanics-Based Structure Analysis of Cyclic Monoterpene Glycosides from Rhodiola rosea

NMR- and MS-guided metabolomic mining for new phytoconstituents from a widely used dietary supplement, Rhodiola rosea, yielded two new (+)-myrtenol glycosides, 1 and 2, and two new cuminol glycosides, 3 and 4, along with three known analogues, 5–7. The structures of the new compounds were determined by extensive spectroscopic data analysis. Quantum mechanics-driven 1H iterative full spin analysis (QM-HiFSA) decoded the spatial arrangement of the methyl groups in 1 and 2, as well as other features not recognizable by conventional methods, including higher order spin-coupling effects. Expanding applied HiFSA methodology to monoterpene glycosides advances the toolbox for stereochemical assignments, facilitates their structural dereplication, and provides a more definitive reference point for future phytochemical and biological studies of R. rosea as a resilience botanical. Application of a new NMR data analysis software package, CT, for QM-based iteration of NMR spectra is also discussed.