1210897-92-9Relevant academic research and scientific papers
Asymmetric Total Synthesis and Biological Evaluation of Proapoptotic Natural Myrcene-Derived Cyclohexenyl Chalcones
Tiamas, Shelly Gapil,Audet, Florian,Samra, Alma Abou,Bignon, Jérome,Litaudon, Marc,Fourneau, Christophe,Ariffin, Azhar,Awang, Khalijah,Desrat, Sandy,Roussi, Fanny
, p. 5830 - 5835 (2018/11/24)
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.
(1R)-(+)-camphor and acetone derived α′-hydroxy enones in asymmetric diels-alder reaction: Catalytic activation by Lewis and bronsted acids, substrate scope, applications in syntheses, and mechanistic studies
Banuelos, Patrcia,Garcia, Jesus M.,Gomez-Bengpa, Enrique,Herrero, Ada,Odriozola, Jose M.,Oiarbide, Mikel,Palomo, Claudio,Razkin, Jesus
supporting information; experimental part, p. 1458 - 1473 (2010/06/11)
Chemical Equation Presented The Diels-Alder reaction constitutes one of the most powerful and convergent C-C bond-forming transformations and continues to be the privileged route to access cyclohexene substructures, which are widespread within natural products and bioactive constituents. Over the recent years, asymmetric catalytic Diels-Alder methodologies have experienced a tremendous advance, but still inherently difficult diene-dienophile combinations prevail, such as those involving dienes less reactive than cyclopentadiene or dienophiles like β-substituted acrylates and equivalents. Here the main features of a'-hydroxy enones as reaction partners of the Diels-Alder reaction are shown, with especial focus on their potentials and limitations in solving the above difficult cases. α'-Hydroxy enones are able to bind reversibly to both Lewis acids and Bronsted acids, forming 1,4-coordinated species that are shown to efficiently engage in these inherently difficult Diels-Alder reactions. On these bases, a convenient control of the reaction stereocontrol can be achieved using a camphor-derived chiral α'-hydroxy enone model (substrate-controlled asymmetric induction) and either Lewis acid or Bronsted acid catalysis. Complementing this approach, highly enantio- and diastereoselective Diels-Alder reactions can also be carried out by using simple achiral α'-hydroxy enones in combination with Evans' chiral Cu(II)BOX complexes (catalyst-controlled asymmetric induction). Of importance, α'-hydroxy enones showed improved reactivity profiles and levels of stereoselectivity (endo/exo and facial selectivity) as compared with other prototypical dienophiles in the reactions involving dienes less reactive than cyclopentadiene. A rationale of some of these results is provided based on both kinetic experiments and quantum calculations. Thus, kinetic measurements of Bronsted acid promoted Diels-Alder reactions of α'-hydroxy enones show a first-order rate with respect to both enone and Bronsted acid promoter. Quantum calculations also support this trend and provide a rational explanation of the observed stereochemical outcome of the reactions. Finally, these fundamental studies are complemented with applications in natural products synthesis. More specifically, a nonracemic synthesis of (-)-nicolaioidesin C is described wherein a Brαnsted acid catalyzed Diels-Alder reaction involving a α'-hydroxy enone substrate is the key step toward the hitherto challenging tri substituted cyclohexene subunit.
