Asymmetric Total Synthesis and Biological Evaluation of Proapoptotic Natural Myrcene-Derived Cyclohexenyl Chalcones
Document Type
Article
Publication Date
1-1-2018
Abstract
Based on a bioinspired asymmetric Diels–Alder cycloaddition using a chiral Evans oxazolidinone, the first total synthesis of both enantiomers of two myrcene-derived cyclohexenyl chalcones, fislatifolione and fislatifolic acid, has been carried out. This strategy was also applied to the total synthesis of nicolaiodesin C. These natural products, as well as their synthetic intermediates, were evaluated by in-vitro affinity displacement assays, based on the modulation of Bcl-xL/Bak, Mcl-1/Bid, and Bcl-2-Bim interactions. This study showed that (+)-fislatifolic acid acts as a dual Bcl-xL/Mcl-1 inhibitor with micromolar activity, and that a Weinreb amide intermediate acts as an excellent Mcl-1/Bcl-2 dual inhibitor at the submicromolar level.
Keywords
Asymmetric synthesis, Biological activity, Chiral auxiliaries, Cycloaddition, Natural products, Total synthesis
Divisions
CHEMISTRY
Publication Title
European Journal of Organic Chemistry
Volume
2018
Issue
42
Publisher
Wiley