Abstract
The sign of optical rotation remains the most common descriptor for chiral molecules, particularly natural products as it has been virtually since the technique was introduced. However, application of the (+) and (-) nomenclature for has been a conundrum almost since its inception for a variety of reasons, including the variation of rotation with wavelength (CD/ORD and null points), the effects of high rotating impurities, and the natural occurrence of racemic/scalemic mixtures. In the case of amines, this is further confounded by possible reversal of sign based on protonation state and/or the presence of optically active counterions in amine salts. We recently encountered just such an issue in assigning the absolute configuration of the poison frog alkaloid phantasmidine, forcing us to revisit the absolute configuration of epibatidine based on a commercial sample that was incorrectly labeled/assigned. Resolution, chiral gas chromatography and x-ray analysis confirmed the literature assignment of epibatidine. However, some revision of the pharmacologic literature will be required. Our results and implications for stereochemistry in the literature will be discussed.