Stereochemistry of spongosoritins: beyond optical rotation

Stereochemical determinations based solely on the comparison of optical rotation (OR) measured at single wavelengths may commonly result in misassignments. Herein, we use vibrational and electronic CD, NMR, OR, and DFT calculations, to confirm the absolute configuration (AC) of the cytotoxic marine polyketides spongosoritin A (1) and 9,10-dihydrospongosoritin A (2) as (−)-(6R,8R) and (−)-(6R,8S), respectively. The AC of natural 1 and 2 has so far relied upon comparisons of OR values only. Besides showing the dependence of OR on achiral structural feautures, such E/Z double bond geometries, an IR spectral marker is provided to help tell apart geometric isomers of related molecules.