Abstract
In this study, the (S)-enantiomers of the aporphine alkaloids, nuciferine and roemerine, were prepared via a synthetic route involving catalytic asymmetric hydrogenation and both stereoisomers were evaluated in vitro for functional activity at human 5-HT(2) and adrenergic α(1) receptor subtypes using a transforming growth factor-α shedding assay. Both enantiomers of each of the compounds were found to act as antagonists at 5-HT(2) and α(1) receptors. (R)-roemerine was the most potent compound at 5-HT(2A) and 5-HT(2C) receptors (pK(b) = 7.8-7.9) with good selectivity compared to (S)-roemerine at these two receptors and compared to its activity at 5-HT(2B), α(1A), α(1B) and α(1D) receptors.