ABSTRACT
Isoparvifuran is a benzofuran compound isolated from the heartwood of Dalbergia odorifera. Related research reported that isoparvifuran has antioxidant property. However, it is unclear whether isoparvifuran has anti-aging effects. In this research, we established an aging model, hydrogen peroxide (H2O2)-induced BJ cell senescence, to explore the protective effect of isoparvifuran on cell senescence and its related mechanisms. Our results revealed that isoparvifuran obviously attenuated H2O2-induced cell senescence, increased the cell proliferation rate,and reversed senescence-associated molecular markers expression such as cyclin D1, pRb, caveolin-1, ace-p53, p21 and p16. Moreover, isoparvifuran dose and time dependently increased the expression level of Sirtuin 1 (SIRT1) in BJ cells. The inhibition of SIRT1 obviously reversed the reduction of SA-ß-gal activity and the alteration of senescence-associated molecular markers induced by isoparvifuran. Additionally, isoparvifuran also inhibited H2O2-induced AKT and S6 phosphorylation and increase of SA-ß-gal activity. In summary, isoparvifuran protects BJ cells from H2O2-induced premature senescence, the anti-senescence effect of isoparvifuran is associated with the activation of SIRT1 and the suppression of AKT/mTOR signaling pathway.
Subject(s)
Antioxidants/pharmacology , Benzofurans/pharmacology , Cellular Senescence/drug effects , Sirtuin 1/metabolism , Antioxidants/isolation & purification , Benzofurans/isolation & purification , Cell Line , Dalbergia/chemistry , Humans , Hydrogen Peroxide/toxicity , Medicine, East Asian Traditional , Plants, Medicinal/chemistry , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , RNA, Small Interfering/genetics , Signal Transduction/drug effects , Sirtuin 1/antagonists & inhibitors , Sirtuin 1/genetics , TOR Serine-Threonine Kinases/antagonists & inhibitorsABSTRACT
(4+3) Cycloadditions have been widely applied in synthesis, and in this review article, we summarize some of the more recent applications, including formal (4+3) cycloadditions, in the synthesis of natural products. Many of these natural product target frameworks have cycloheptane subunits, for which the (4+3) cycloaddition is a convergent strategy for their assembly. Some natural product targets do not possess seven membered rings, and their syntheses have exploited the functional group endowed (4+3) cycloadducts resulting from these reactions, highlighting the utility of this methodology for the synthesis of a range of complex molecules.
Subject(s)
Biological Products/chemical synthesis , Cycloheptanes/chemical synthesis , Biological Products/chemistry , Cycloaddition Reaction , Cycloheptanes/chemistry , Molecular StructureABSTRACT
A first example of Pd-catalyzed gem-difluoroallylation of organoborons using 3-bromo-3,3-difluoropropene (BDFP) in high efficiency with high α/γ-substitution regioselectivity has been developed. The reaction can also be extended to substituted BDFPs and has advantages of low catalyst loading (0.8 to 0.01 mol %), broad substrate scope, and excellent functional group compatibility, thus providing a facile route for practical application in drug discovery and development.
Subject(s)
Alkenes/chemistry , Boron Compounds/chemistry , Hydrocarbons, Halogenated/chemistry , Hydrocarbons, Halogenated/chemical synthesis , Organometallic Compounds/chemistry , Palladium/chemistry , Catalysis , Molecular StructureABSTRACT
A general and efficient method for the highly enantioselective alkynylation of ketoimines through a zinc/1,1'-bi-2-naphthol (BINOL)-catalyzed process has been developed. A variety of ketoimines, including α-fluoroalkyl α-imine esters, α-aryl α-imine esters, and trifluoromethyl aryl ketoimines, are applicable and provide their corresponding quaternary propargyl amines in excellent yields with high ee values (up to 99 % ee). Both the steric and electronic effects of substituents at the 3,3' positions of BINOL are critical for the reaction efficiency and enantioselectivity. To demonstrate the usefulness of the method, (R)-α-CF3 α-proline has been prepared in a highly efficient manner. The notable features of this protocol are its broad substrate scope, high reaction efficiency (up to 99 %) and enantioselectivity (up to 99 % ee), low catalyst loading (5 mol % of BINOL derivative), and mild reaction conditions.
Subject(s)
Alkynes/chemistry , Amines/chemistry , Imines/chemistry , Ketones/chemistry , Naphthols/chemistry , Zinc/chemistry , Catalysis , Molecular Structure , StereoisomerismABSTRACT
The title compound, C(11)H(14)F(2)O(4), is a γ,γ-gem-difluorinated α,ß-unsaturated δ-lactone. The dioxolane five-membered ring and the lactone ring adopt half-chair conformations. There are two inter-molecular C-Hâ¯O inter-actions involving the carbonyl group as an acceptor which stabilize the crystal structure.
