Raman optical activity of a flavone C-diglycoside: Aqueous solution conformations and absolute configuration

Abstract

A B S T R A C TThe combination of experimental and theoretical Raman optical activity data for the flavone Cdiglycoside isoswertisin-4 0 -methyl-ether-2 00 a-L-rhamnoside provided detailed information about its conformational preferences in aqueous solution as well as the absolute configuration of the glycosidic linkage. This work also demonstrated the importance of explicit solvation for accurate predictions of the conformational ensemble and vibrational optical activity properties of natural products in water, as opposed to gas-phase or polarizable continuum model calculations.

Paving the way to conformationally unravel complex glycopeptide antibiotics by means of Raman optical activity

“…The difference between vancomycin and other systems containing aromatic systems that have been studied by ROA is the presence of a relative large amount of aromatic rings (ve) that are locked in certain orientations. 18,28 Our estimation is that this particular geometrical feature places the aromatic rings in a dominant position in the ROA contributions. If one is, however, not particularly interested in the carbohydrate's conformation, the ROA technique has the benet of focusing specically on the rest of the molecule.…”

“…The standard approach that has been established for applying chiroptical techniques in the conformational determination of (relatively) small compound runs as follows: (1) record an experimental spectrum, (2) conduct a conformational analysis by collecting experimentally available ensembles and/ or use conformer generator programs (3) optimize the geometries and calculate spectra with DFT methods, and (4) identify the best matching single-conformer or Boltzmann-weighed spectrum with the experiment. 5,[27][28][29] Adhering to this strategy is a very effective way to answer the central question of what (set of) conformation(s) is adopted by the compound. This approach is, however, not infallible, especially with a growing molecular complexity of the compounds.…”