RESUMEN
Epimedium brevicornum Maxim has a long history of use in the treatment of estrogen deficiency-related diseases. However, the chemical constituents and mechanism of action of this medicinal plant are not fully understood. In the present study, we isolated four new isoprenylated flavonoid glycosides, as well as 16 known flavonoids (13 isoprenylated flavonoids), from this plant. The chemical structures of the new flavonoid glycosides were elucidated by extensive spectroscopic analysis. The new compounds 1-4 were potent promoters of estrogen biosynthesis in human ovarian granulosa-like KGN cells. ZW1, an isoprenylated flavonoid analogue and a specific inhibitor of phosphodiesterase 5 (PDE5), was synthesized and used to explore the mechanism of the isoprenylated analogues on estrogen biosynthesis. ZW1 treatment increased estrogen production by upregulation of aromatase mRNA and protein expression. ZW1 increased the phosphorylation of cAMP response element-binding protein (CREB). Further study showed that the inhibition of PDE5 by ZW1 increased estrogen biosynthesis partly through suppression of phosphodiesterase 3 (PDE3). Our results suggested that the isoprenylated flavonoids from E. brevicornum may produce beneficial health effects through the promotion of estrogen biosynthesis. PDE5 warrants further investigation as a new therapeutic target for estrogen biosynthesis in the prevention and treatment of estrogen-deficiency related diseases.
Asunto(s)
Epimedium/química , Estrógenos/biosíntesis , Flavonoides/farmacología , Glicósidos/farmacología , Células de la Granulosa/efectos de los fármacos , Inhibidores de Fosfodiesterasa/farmacología , Línea Celular , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Femenino , Flavonoides/química , Glicósidos/química , Células de la Granulosa/metabolismo , Humanos , Inhibidores de Fosfodiesterasa/química , Plantas Medicinales/químicaRESUMEN
In the title N-heterocyclic carbene compound, C(32)H(30)N(4) (2+)·2PF(6) (-), the mean plane of the naphthalene ring system makes dihedral angles of 79.15â (15) and 76.85â (16) with the imidazole rings and 56.15â (19) and 80.56â (16)° with the benzene rings. An intra-molecular C-Hâ¯N hydrogen bond occurs. The crystal structure is stabilized by C-Hâ¯F inter-actions. In addition, π-π inter-actions [centroid-centroid distances = 3.848â (1) and 3.574â (3)â Å] are observed. The nine equatorial F atoms in the two PF(6) (-) anions were disordered over two positions with occupancy ratios of 0.545â (10):0.455â (10) and 0.793â (11):0.207â (11) in the two anions.
RESUMEN
In the title salt, C(23)H(23)N(2)O(+)·PF(6) (-), the PF(6) (-) anion is highly disordered (occupancy ratios of 0.35:0.35:0.3, 0.7:0.15:0.15, 0.7:0.3 and 0.35:0.35:0.15:0.15) with the four F atoms in the equatorial plane rotating about the axial F-P-F bond. The mean plane of the imidazole ring makes dihedral angles of 82.44â (17) and 14.39â (16)°, respectively, with the mean planes of the benzene ring and the naphthalene ring system. The crystal structure is stabilized by C-Hâ¯F hydrogen bonds. In addition, π-π [centroid-centroid distances = 3.7271â (19)-3.8895â (17)â Å] and C-Hâ¯π inter-actions are observed.
RESUMEN
Homoprolinol analogs, a class of optically active γ-amino alcohols, were examined systematically in the enantioselective addition reactions of diethylzinc to aldehydes. By comparison of the results catalyzed by these γ-amino alcohols with those by the ß-amino alcohols based on pyrrolidine architecture reported in the literature references, we have observed that the γ-amino alcohols are superior to the corresponding ß-amino alcohols when the nitrogen and the oxygen are unsubstituted. Among the homoprolinols we tested, gave the best results (45-88% yields, 44-81% ee) in the addition reactions. To the best of our knowledge, has been noticed as one of the most efficient γ-amino alcohol catalysts based on pyrrolidine framework.