- Synthesis of Flavonols via Pyrrolidine Catalysis: Origins of the Selectivity for Flavonol versus Aurone
-
A novel synthetic method for flavonol from 2′-hydroxyl acetophenone and benzaldehyde promoted by pyrrolidine under an aerobic condition in water is established. This protocol was supported by efficient synthesis of 44 common examples and three natural products. The α, β-unsaturated iminium ion (enimine ion E) was proved to be the key intermediate in the reaction. H218O and 18O2 isotope tracking experiments demonstrated that both water and the aerobic atmosphere were necessary to ensure the transformation. The selectivity for flavonol or aurone was originated from solvent-triggered intermediates, which were determined by UV-visible spectra from isolated enimine. The phenol-iminium E-A is dominant in water and the ketoenamine intermediate E-B is prevalent in acetonitrile. In the presence of pyrrolidine and oxygen, E-A leads to flavonol through E-I, a zwitterionic-like phenoloxyl-iminium ion, following the key steps of cyclization and a [2 + 2] oxidation; E-B proceeds through path II, a radical process induced by photolysis of E-B with both pyrrolidine and oxygen, to afford aurone. Preliminary mechanistic studies are reported.
- Xiong, Wei,Wang, Xiaohong,Shen, Xianyan,Hu, Cuifang,Wang, Xin,Wang, Fei,Zhang, Guolin,Wang, Chun
-
supporting information
p. 13160 - 13176
(2020/11/23)
-
- Discovery of a Prenylated Flavonol Derivative as a Pin1 Inhibitor to Suppress Hepatocellular Carcinoma by Modulating MicroRNA Biogenesis
-
Peptidyl-prolyl cis-trans isomerase Pin1 plays a crucial role in the development of human cancers. Recently, we have disclosed that Pin1 regulates the biogenesis of miRNA, which is aberrantly expressed in HCC and promotes HCC progression, indicating the therapeutic role of Pin1 in HCC therapy. Here, 7-(benzyloxy)-3,5-dihydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-en-1-yl)-4H-chromen-4-one (AF-39) was identified as a novel Pin1 inhibitor. Biochemical tests indicate that AF-39 potently inhibits Pin1 activity with an IC50 values of 1.008 μm, and also displays high selectivity for Pin1 among peptidyl prolyl isomerases. Furthermore, AF-39 significantly suppresses cell proliferation of HCC cells in a dose- and time-dependent manner. Mechanistically, AF-39 regulates the subcellular distribution of XPO5 and increases miRNAs biogenesis in HCC cells. This work provides a promising lead compound for HCC treatment, highlighting the therapeutic potential of miRNA-based therapy against human cancer.
- Zheng, Yuanyuan,Pu, Wenchen,Li, Jiao,Shen, Xianyan,Zhou, Qiang,Fan, Xin,Yang, Sheng-Yong,Yu, Yamei,Chen, Qiang,Wang, Chun,Wu, Xin,Peng, Yong
-
supporting information
p. 130 - 134
(2018/11/30)
-
- The detection of the precursors of the photorearranged products of 3-hydroxyflavones in selected solvents from UV-visible spectra: In situ
-
Mechanistic studies relating to the photochemistry of 3-hydroxy-2-phenyl-4H-chromen-4-one (3HF) and 6-chloro-3-hydroxy-2-phenyl-4H-chromen-4-one (Cl-3HF) have been reinvestigated in selected solvents. The UV-visible spectra of the photoproduct(s) of 3HF and Cl-3HF have been computed in situ via subtracting the spectra of unreacted substrates, with acetonitrile (ACN) and methanol (MeOH) as solvents. These spectra turn out to be different from the spectra of the corresponding isolated photoproducts: 3-hydroxy-3-phenyl-indan-1,2-dione and 6-chloro-3-hydroxy-3-phenyl-indan-1,2-dione (referred to as dione). Analyses of the photoproduct(s) via GC-MS show the formation of a single detectable product, i.e., the corresponding dione. On the basis of some experimental observations, it is proposed that the primary photoproduct in situ is 2,3-epoxy-2-hydroxy-1-indanone (referred to as epoxide) instead of dione as reported in previous years. Earlier, epoxide has been proposed to be the intermediate in the mechanism for the formation of dione. This is the first report where the formation of epoxide has been directly detected in the selected solvents. On the other hand, both dione and epoxide (2?:?1) are shown to be formed with MeOH as solvent. The second important finding is that epoxide and dione interconvert in the dark, depending upon the environment. With ACN as solvent, pure dione in the dark is kinetically and partially converted to epoxide. With MeOH as solvent, epoxide is instantly and partially converted to dione until both are in equilibrium. However, a solution of dione in MeOH remains stable in the dark. The photoformation of epoxide is quantitative with ACN as solvent and it is sufficiently stable. It has been further observed that epoxide solutions of 3HF and Cl-3HF in ACN are quantitatively converted into 3-phenylisobenzofuran-1(3H)-one and 6-chloro-3-phenylisobenzofuran-1(3H)-one, i.e., the corresponding phthalides, through the loss of CO when kept in the dark for some days. A mechanism has been proposed where epoxide has been shown to give dione and/or phthalide via selective C-O or C-C bond cleavage in the oxiranyl ring, respectively. The selection of this cleavage depends mainly on the solvent system and the substituents in the parent flavones.
- Tomar, Jyoti,Kaur, Kulvir,Bansal, Manisha
-
p. 2912 - 2920
(2019/12/24)
-
- Absorption and fluorescent studies of 3-hydroxychromones
-
The synthesis and spectral studies of variously substituted 3-hydroxychromones have been carried out. A key relationship between the structural motif of synthesized 3-hydroxychromones (3-HCs) and their fluorescent properties was found. The chromones substituted with electron-donating group at 4′-position expressed the red shift of the N and T band and also exhibited the increased fluorescent intensity ratio while the chromones with electron-withdrawing group showed the blue shift of the N and T band. Therefore, these 3-HCs may behave as the possible fluorescent probes.
- Khanna, Radhika,Kumar, Ramesh,Dalal, Aarti,Kamboj, Ramesh C.
-
p. 1159 - 1163
(2015/10/20)
-
- Synthesis of novel flavone acyl esters and correlation of log P value with antioxidant and antimicrobial activity
-
Three series of flavones namely 6-hydroxy flavone, 6-chloro-3-hydroxy flavone, 3,6-dihydroxy flavone were synthesized. They were further benzoylated with different aromatic acid chlorides in the presence of pyridine gave three of acyl esters series (SCF 1 to 8, SHF 1 to 8 and SDF 1 to 8). The yields of all the substituted flavones were found satisfactory. These compounds were purified, characterized by their spectral data. log P and pKa value. They were screened for in vitro radical (DPP?) scavenging activity, showed appreciable activity. 7 compounds showed antimicrobial activity against Gram-positive bacteria. Further, the MIC values of these 7 compounds were also determined. All the compounds showing antioxidant activity also showed antibacterial activity. The relationship between log P, antioxidant and antibacterial activity was established.
- Jayashree,Thejaswini,Nayak, Yogendra,Kumar, D. Vijay
-
experimental part
p. 1055 - 1066
(2012/03/26)
-
- COMPOUNDS FOR IMMUNOPOTENTIATION
-
Methods of stimulating an immune response and treating patients responsive thereto with 3,4-di(1H-indol-3-yl)-1H-pyrrole-2,5-diones, staurosporine analogs, derivatized pyridazines, chromen-4-ones, indolinones, quinazolines, nucleoside analogs, and other small molecules are disclosed.
- -
-
Page/Page column 123
(2010/02/15)
-
- C-3 Hydroxylation of flavones using hypervalent iodine oxidation
-
Hypervalent iodine oxidation of several flavones (1b-g) with iodobenzene diacetate in methanolic potassium hydroxide, followed by acid hydrolysis of the resultant 3-hydroxy-2-methoxyflavonones dimethylacetals (2b-g), offers a general method for 3-hydroxyflavones (3b-g).
- Prakash, Om,Pahuja, Saroj,Tanwar, Madan P
-
p. 272 - 273
(2007/10/02)
-