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

[Image: see text] 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 a...

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Autores principales: Brown, Carla E., Kong, Tiffany, Britten, James F., Werstiuk, Nick H., McNulty, James, D’Aiuto, Leonardo, Demers, Matthew, Nimgaonkar, Vishwajit L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2018
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173499/
https://www.ncbi.nlm.nih.gov/pubmed/30320263
http://dx.doi.org/10.1021/acsomega.8b01987
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author Brown, Carla E.
Kong, Tiffany
Britten, James F.
Werstiuk, Nick H.
McNulty, James
D’Aiuto, Leonardo
Demers, Matthew
Nimgaonkar, Vishwajit L.
author_facet Brown, Carla E.
Kong, Tiffany
Britten, James F.
Werstiuk, Nick H.
McNulty, James
D’Aiuto, Leonardo
Demers, Matthew
Nimgaonkar, Vishwajit L.
author_sort Brown, Carla E.
collection PubMed
description [Image: see text] 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.
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spelling pubmed-61734992018-10-11 Asymmetric Entry into 10b-aza-Analogues of Amaryllidaceae Alkaloids Reveals a Pronounced Electronic Effect on Antiviral Activity Brown, Carla E. Kong, Tiffany Britten, James F. Werstiuk, Nick H. McNulty, James D’Aiuto, Leonardo Demers, Matthew Nimgaonkar, Vishwajit L. ACS Omega [Image: see text] 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. American Chemical Society 2018-09-20 /pmc/articles/PMC6173499/ /pubmed/30320263 http://dx.doi.org/10.1021/acsomega.8b01987 Text en Copyright © 2018 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Brown, Carla E.
Kong, Tiffany
Britten, James F.
Werstiuk, Nick H.
McNulty, James
D’Aiuto, Leonardo
Demers, Matthew
Nimgaonkar, Vishwajit L.
Asymmetric Entry into 10b-aza-Analogues of Amaryllidaceae Alkaloids Reveals a Pronounced Electronic Effect on Antiviral Activity
title Asymmetric Entry into 10b-aza-Analogues of Amaryllidaceae Alkaloids Reveals a Pronounced Electronic Effect on Antiviral Activity
title_full Asymmetric Entry into 10b-aza-Analogues of Amaryllidaceae Alkaloids Reveals a Pronounced Electronic Effect on Antiviral Activity
title_fullStr Asymmetric Entry into 10b-aza-Analogues of Amaryllidaceae Alkaloids Reveals a Pronounced Electronic Effect on Antiviral Activity
title_full_unstemmed Asymmetric Entry into 10b-aza-Analogues of Amaryllidaceae Alkaloids Reveals a Pronounced Electronic Effect on Antiviral Activity
title_short Asymmetric Entry into 10b-aza-Analogues of Amaryllidaceae Alkaloids Reveals a Pronounced Electronic Effect on Antiviral Activity
title_sort asymmetric entry into 10b-aza-analogues of amaryllidaceae alkaloids reveals a pronounced electronic effect on antiviral activity
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173499/
https://www.ncbi.nlm.nih.gov/pubmed/30320263
http://dx.doi.org/10.1021/acsomega.8b01987
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