Identification of rapid access to polycyclic systems via a base-catalyzed cascade cyclization reaction and their biological evaluation.
Acrolein
/ chemistry
Antineoplastic Agents
/ chemical synthesis
Cell Line, Tumor
Cell Proliferation
/ drug effects
Cyclization
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Esters
/ chemistry
Humans
Malonates
/ chemistry
Models, Molecular
Molecular Structure
Polycyclic Compounds
/ chemical synthesis
Structure-Activity Relationship
Journal
Bioorganic chemistry
ISSN: 1090-2120
Titre abrégé: Bioorg Chem
Pays: United States
ID NLM: 1303703
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
27
01
2020
revised:
08
04
2020
accepted:
09
04
2020
pubmed:
26
4
2020
medline:
3
3
2021
entrez:
26
4
2020
Statut:
ppublish
Résumé
A base-mediated cascade reaction between malonate esters and acrolein was developed to access complex polycyclic systems. This novel tandem reaction enables the simultaneous generation of up to seven new bonds and at least three new stereogenic centers. Mechanistic studies indicate a series of nucleophilic 1,4 and 1,6 Michael addition reactions occur, followed by an aldol condensation reaction, culminating in the formation of three fused rings. The compounds were characterized by NMR studies and the stereochemistry was confirmed by X-ray analysis. The ability to generate multigram quantities of such complex molecular scaffolds renders the method promising for medicinal chemistry campaigns. Herein, we also demonstrate that the lead compounds display promising anti-proliferative activities against human cancer cell models.
Identifiants
pubmed: 32334195
pii: S0045-2068(20)30192-9
doi: 10.1016/j.bioorg.2020.103846
pmc: PMC7329093
mid: NIHMS1589140
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Esters
0
Malonates
0
Polycyclic Compounds
0
Acrolein
7864XYD3JJ
malonic acid
9KX7ZMG0MK
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
103846Subventions
Organisme : NCI NIH HHS
ID : P30 CA021765
Pays : United States
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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