Asymmetric Entry into 10b‑aza-Analogues of Amaryllidaceae Alkaloids Reveals a Pronounced Electronic Effect on Antiviral Activity

Development of a chiral pool-based synthesis of 10b-aza-analogues of biologically active Amaryllidaceae alkaloids is described, involving a concise reductive amination and condensation sequence, leading to ring-B/C-modified, fully functionalized ring-C derivatives. Differentiated anticancer and anti...

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Bibliographic Details
Published in:ACS omega 2018-09, Vol.3 (9), p.11469-11476
Main Authors: Brown, Carla E, Kong, Tiffany, Britten, James F, Werstiuk, Nick H, McNulty, James, D’Aiuto, Leonardo, Demers, Matthew, Nimgaonkar, Vishwajit L
Format: Article
Language:English
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Summary:Development of a chiral pool-based synthesis of 10b-aza-analogues of biologically active Amaryllidaceae alkaloids is described, involving a concise reductive amination and condensation sequence, leading to ring-B/C-modified, fully functionalized ring-C derivatives. Differentiated anticancer and antiviral activities of these analogues are presented. Despite complete conformational and functional group overlap, the 10b-aza-analogues have diminished anticancer activity and no antiviral activity. These unprecedented electronic effects suggest a possible role for π-type secondary orbital interactions with the biological target.
ISSN:2470-1343
2470-1343
DOI:10.1021/acsomega.8b01987