Synthesis and evaluation of nuciferine and roemerine enantiomers as 5-HT2 and α1 receptor antagonists†
Hui Li
Heng, 
a
Chin Fei
Chee,
ab
Sek Peng
Chin,
ab
Michael J. C.
Buckle,
*a
Deron R.
Herr,
d
Ian C.
Paterson,
e
Stephen W.
Doughty,
f
Noorsaadah
Abd. Rahman
b
and
a
Chin Fei
Chee,
ab
Sek Peng
Chin,
ab
Michael J. C.
Buckle,
*a
Deron R.
Herr,
d
Ian C.
Paterson,
e
Stephen W.
Doughty,
f
Noorsaadah
Abd. Rahman
b
and
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-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-HT2A and 5-HT2C receptors (pKb = 7.8–7.9) with good selectivity compared to (S)-roemerine at these two receptors and compared to its activity at 5-HT2B, α1A, α1B and α1D receptors.
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