Absolute configuration of natural products through quantum chemical calculation of CD spectra-selected examples

Chiroptical methods such as electronic circular dichroism (ECD) has been used for assignment of absolute configuration since several decades, but were limited in their applicability. Recent progress in the areas of conformational analysis and time dependent density function theory (TDTDF) calculation allows prediction of CD spectra by quantum chemical calculations. This is especially valuable for the analysis of new molecular entities when chemical synthesis of the reference compound is not an alternative. We successfully applied this methodology to establish the absolute configuration of structurally diverse and conformationally rigid or flexible molecules including monoterpenes, sesquiterpene coumarins, bisabolol sesquiterpenes, and complex isoprenoids with novel scaffolds. With a series of bisabolol oxide esters we demonstrate the assignment of absolute configuration by ECD calculation for compounds in which relative stereochemistry of two discrete parts of the molecule but not of its entirety could be established by NMR.