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Structure Revision and Biological Evaluation of Artabonatine A and Its Diastereoisomer
Author(s) -
Ku Angela,
Cuny Gregory
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.766.10
Subject(s) - diastereomer , chemistry , natural product , stereochemistry , monoamine neurotransmitter , biological activity , g protein coupled receptor , receptor , in vitro , combinatorial chemistry , biochemistry , serotonin
Aporphines are a privileged scaffold, with many of these alkaloids demonstrating affinity for G‐protein coupled receptors (GPCRs) and monoamine transporters. A series of 7‐oxygenated aporphines possessing either anti ‐ or syn ‐configurations between protons 6a and 7 have been identified in nature, but their pharmacology has not been extensively studied. In order to explore their bioactivities, a synthesis was established by utilizing a one‐pot reductive acid‐mediated cyclization followed by a palladium‐mediated ortho ‐phenol arylation. Using this methodology both diastereomeric isomers of (–)‐artabonatine A were prepared and the configuration of the natural product was revised from anti to syn based on comparison of NMR spectral data and specific rotations. In addition, (±)‐artabonatine A and epi ‐(±)‐artabonatine A exhibited different in vitro pharmacological activities when screened against a panel of forty‐five GPCR and monoamine transporter targets, demonstrating that a small change in relative stereochemistry had a dramatic effect on molecular selectivity. These results also highlight the benefit of preparing natural products and non‐natural isomers.Biological difference between (±)‐ artabonatine A ( syn ‐ siomer) and epi ‐(±)‐ artabonatine A ( anti ‐ isomer)