Synthesis and evaluation of nuciferine and roemerine enantiomers as 5-HT₂ and α₁ receptor antagonists

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-HT₂ and adrenergic α₁ 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-HT₂ and α₁ 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.