Correlations among experimental and theoretical NMR data to determine the absolute stereochemistry of darcyribeirine, a pentacyclic indole alkaloid isolated from Rauvolfia grandiflora

• Geometry optimizations were carried out using BLYP/6-31G* calculations.
• Solvent effect (DMSO) was initially investigated by use of an explicit model.
• The PCM model was also used to investigate the solvent effect.
• Calculated and experimental carbon chemical shifts were correlated.
• Optical rotation calculations indicated the absolute stereochemistry.

Darcyribeirine (1) is a pentacyclic indole alkaloid isolated from Rauvolfia grandiflora. Stereochemistry of 1 was previously proposed based on 1D (coupling constant data) and 2D (NOESY correlations) NMR techniques, having been established a configuration 3R, 15S, and 20R (isomer 1a). Stereoisomers of 1 (i.e., 1a–1h) can be grouped into four sets of enantiomers. Carbon chemical shifts and hydrogen coupling constants were calculated using BLYP/6-31G* theory level for the eight isomers of 1. Calculated NMR data of 1a–1h were correlated with the corresponding experimental data of 1. The best correlations between theoretical and experimental carbon chemical shift data were obtained for the set of enantiomers 1e/1f to structures in the gaseous phase and considering solvent effects (using PCM and explicit models). Similar results were obtained when the same procedure was performed to correlations between theoretical and experimental coupling constant data. Finally, optical rotation calculations indicate 1e as its absolute stereochemistry. Orbital population analysis indicates that the hydrogen bonding between N–H of 1e and DMSO is due to contributions of its frontier unoccupied molecular orbitals, mainly LUMO+1, LUMO+2, and LUMO+3.

Solvent effects on the LUMO+3 of darcyribeirine and system darcyribeirine–DMSO.Figure optionsDownload as PowerPoint slide