(+)- and (−)-Ecarlottones, Uncommon Chalconoids from Fissistigma latifolium with Pro-Apoptotic Activity

Abstract

Four new compounds, (+)- and (-)-ecarlottone (1), (±)-fislatifolione (5), (±)-isofislatifolione (6), and (±)-fislatifolic acid (7), and the known desmethoxyyangonin (2), didymocarpin-A (3), and dehydrodidymocarpin-A (4) were isolated from the stem bark of Fissistigma latifolium, by means of bioassay-guided purification using an in vitro affinity displacement assay based on the modulation of Bcl-xL/Bak and Mcl-1/Bid interactions. The structures of the new compounds were elucidated by NMR spectroscopic data analysis, and the absolute configurations of compounds (+)-1 and (-)-1 were assigned by comparison of experimental and computed ECD spectra. (-)-Ecarlottone 1 exhibited a potent antagonistic activity on both protein-protein associations with K values of 4.8 μM for Bcl-xL/Bak and 2.4 μM for Mcl-1/Bid.

Asymmetric Total Synthesis and Biological Evaluation of Proapoptotic Natural Myrcene‐Derived Cyclohexenyl Chalcones

“…for C 19 H 25 O 2 [M + H] + 285.1849; found 285.1848. The characterization data are identical to those reported in ref …”

“…All the natural products prepared, as well as all the 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 (Table ). In addition to its good affinities towards Bcl‐xL and Mcl‐1, (±)‐ecarlottone ( 1 ) was found to be a good inhibitor of Bcl‐2. No difference was observed between the behaviour of racemic fislatifolione ( 2 ) and its enantiomers.…”

“…Indeed, our laboratory has a longstanding interest in the discovery of proapoptotic compounds targeting Bcl‐2 family proteins, which have shown potential as targets for the treatment of various cancers . Recently, four new cyclohexenyl chalcones, including (±)‐ecarlottone ( 1 ), (±)‐fislatifolione ( 2 ), and (±)‐fislatifolic acid ( 3 ; Figure ) were isolated from the stem bark of Fissistigma latifolium , by bioassay‐guided purification using an in‐vitro affinity displacement assay based on the modulation of Bcl‐xL/Bak and Mcl‐1/Bid interactions . These plant secondary metabolites, probably formed through a Diels–Alder cycloaddition between the diene myrcene ( 4 ) and various chalcones ( 5 ), are new members of the cyclohexenyl chalcone family, which includes panduratins, crinatusins, fissistins, schefflerin, krachaizins, and nicolaiodesins.…”

Novel Bisamide Alkaloids Enantiomers from Pepper Roots (Piper nigrum L.) with Acetylcholinesterase Inhibitory and Anti-Neuroinflammatory Effects

“…Diels–Alder reaction in biosynthesis is a crucial step in the creation of enantiomers in nature. − Biomimetic synthesis of bisamide alkaloids with six-membered rings and four different chiral centers from piperine through an intermolecular Diels–Alder reaction is possible . In this work, the biomimetic transition between two distinct monomeric amide alkaloids was effectively accomplished.…”

Terpenoids from the Stems of Fissistigma polyanthoides and Their Anti-Inflammatory Activity

“…The relative configuration between C-1 and C-2 was determined as trans due to a large coupling constant of 10.6 Hz [δ H 3.04 (1H, td, J = 10.6, 5.6 Hz, H-1), 2.82 (1H, td, J = 10.6, 8.4 Hz, H-2)]. Notably, the NMR data of 10 were found to be identical to those of (±)-fislatifolic acid, 12 although this previous publication only reported the isolation of a racemic mixture. Since compound 10 showed an optical rotation ([α] D 20 −12.0, c 0.07, CHCl 3 ) and a clear CD spectrum, it was determined that compound 10 is optically active.…”