- Total synthesis of kaempferol and methylated kaempferol derivatives
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Kaempferol (1), a natural product from various plants, was synthesized in which the longest linear sequence is only seven steps in overall yields of 47% from commercially available 1,3,5-trimethoxybenzene (10). The methylated kaempferols 2-5 were also prepared by use of this concise synthetic methodology. The key transformations in this synthesis involved the I2 oxidative-promoting-cyclization and DDO oxidative hydroxylation. Several strategies to achieve 1 are provided.
- Lee, Yean-Jang,Wu, Tsao-Dong
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- Dual-Targeting Antiproliferation Hybrids Derived from 1-Deoxynojirimycin and Kaempferol Induce MCF-7 Cell Apoptosis through the Mitochondria-Mediated Pathway
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1-Deoxynojirimycin, an α-glucosidase inhibitor, possesses various biological activities such as antitumor, antidiabetic, and antiviral effects. However, the application of 1-deoxynojirimycin is restricted by its poor lipophilicity and low bioavailability.
- Attaribo, Thomas,Gui, Zhongzheng,Huang, Gaiqun,Jin, Byung Rae,Lee, Kwang Sik,Tang, Liumei,Xin, Xiangdong,Zeng, Qinglei,Zhang, Ning,Zhang, Ran,Zhang, Yueyue
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- Flavonol glycosides from Cassia hirsuta
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A new flavonol glycoside, kaempferol 3-O-α-L-rhamnopyranosyl (1→2)- α-L-rhamnopyranoside (1), was isolated from the flowers of Cassia hirsuta along with two known flavonol glycosides, kaempferol 3-O-rutinoside and rutin. The structure of compound 1 has been established on the basis of spectral data and by acid hydrolysis.
- Rao,Damu,Jayaprakasam,Gunasekar
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- MASS SPECTROMETRY IN THE STRUCTURAL DETERMINATION OF FLAVONOL TRIGLYCOSIDES FROM VINCA MAJOR
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Key Word Index-Vinca major; Apocynaceae; leaves; flavonol glycosides; kaempferol 3-O-(6''-O-rhamnosyl)-galactosides 7-O-glucoside; chlorogenic acid; mass spectrometry.Chlorogenic acid, robinin and flavonol triglycoside were isolated from the leaves of Vinca major.The structure of the triglycoside was determined to be kaempferol 3-O-(6''-rhamnopyranosyl)-galactopyranoside 7-O-glucopyranoside by fast atom bombardment, electron impact and negative ion desorption chemical ionization mass spectropetry.
- Sakushima, Akiyo,Nishibe, Sansei
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- Synthesis of Flavonols via Pyrrolidine Catalysis: Origins of the Selectivity for Flavonol versus Aurone
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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
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supporting information
p. 13160 - 13176
(2020/11/23)
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- 1-deoxynojirimycin-kaempferol compound, intermediate, preparation method and application
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The invention discloses a 1-deoxynojirimycin-kaempferol compound, an intermediate, a preparation method and application. The structural formula of the compound is as shown in the specification. In thestructural formula, R is -CnH2n-, n is an integer, and
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Paragraph 0037; 0040; 0048-0053
(2020/12/31)
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- Intercepted Retro-Nazarov Reaction: Syntheses of Amidino-Rocaglate Derivatives and Their Biological Evaluation as eIF4A Inhibitors
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Rocaglates are a family of natural products isolated from the genus Aglaia which possess a highly substituted cyclopenta[b]benzofuran skeleton and inhibit cap-dependent protein synthesis. Rocaglates are attractive compounds due to their potential for inhibiting tumor cell maintenance in vivo by specifically targeting eukaryotic initiation factor 4A (eIF4A) and interfering with recruitment of ribosomes to mRNA. In this paper, we describe an intercepted retro-Nazarov reaction utilizing intramolecular tosyl migration to generate a reactive oxyallyl cation on the rocaglate skeleton. Trapping of the oxyallyl cation with a diverse range of nucleophiles has been used to generate over 50 novel amidino-rocaglate (ADR) and amino-rocaglate derivatives. Subsequently, these derivatives were evaluated for their ability to inhibit cap-dependent protein synthesis where they were found to outperform previous lead compounds including the rocaglate hydroxamate CR-1-31-B.
- Zhang, Wenhan,Chu, Jennifer,Cyr, Andrew M.,Yueh, Han,Brown, Lauren E.,Wang, Tony T.,Pelletier, Jerry,Porco, John A.
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p. 12891 - 12900
(2019/09/09)
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- Flavone derivative and medical application thereof
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The invention provides a flavone derivative and medical application thereof, and belongs to the technical field of medicines. Specifically, the invention relates to a compound as shown in a formula Iand a pharmacological effect thereof for regulating cell
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Paragraph 0014-0015
(2019/08/12)
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- Chemical Synthesis Enables Structural Reengineering of Aglaroxin C Leading to Inhibition Bias for Hepatitis C Viral Infection
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As a unique rocaglate (flavagline) natural product, aglaroxin C displays intriguing biological activity by inhibiting hepatitis C viral entry. To further elucidate structure-activity relationships and diversify the pyrimidinone scaffold, we report a concise synthesis of aglaroxin C utilizing a highly regioselective pyrimidinone condensation. We have prepared more than 40 aglaroxin C analogues utilizing various amidine condensation partners. Through biological evaluation of analogues, we have discovered two lead compounds, CMLD012043 and CMLD012044, which show preferential bias for the inhibition of hepatitis C viral entry vs translation inhibition. Overall, the study demonstrates the power of chemical synthesis to produce natural product variants with both target inhibition bias and improved therapeutic indexes.
- Zhang, Wenhan,Liu, Shufeng,Maiga, Rayelle I.,Pelletier, Jerry,Brown, Lauren E.,Wang, Tony T.,Porco, John A.
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supporting information
p. 1312 - 1323
(2019/01/21)
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- Synthesis and biological evaluation of flavones and benzoflavones as inhibitors of BCRP/ABCG2
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Multidrug resistance (MDR) often leads to a failure of cancer chemotherapy. Breast Cancer Resistance Protein (BCRP/ABCG2), a member of the superfamily of ATP binding cassette proteins has been found to confer MDR in cancer cells by transporting molecules with amphiphilic character out of the cells using energy from ATP hydrolysis. Inhibiting BCRP can be a solution to overcome MDR.We synthesized a series of flavones, 7,8-benzofl avones and 5,6-benzo flavones with varying substituents at positions 3, 3′ and 4′ of the (benzo)fl avone structure. All synthesized compounds were tested for BCRP inhibition in Hoechst 33342 and pheophorbide A accumulation assays using MDCK cells expressing BCRP. All the compounds were further screened for their P-glycoprotein (P-gp) and Multidrug resistance-associated protein 1 (MRP1) inhibitory activity by calcein AM accumulation assay to check the selectivity towards BCRP. In addition most active compounds were investigated for their cytotoxicity. It was observed that in most cases 7,8-benzoflavones are more potent in comparison to the 5,6-benzoflavones. In general it was found that presence of a 3-OCH3 substituent leads to increase in activity in comparison to presence of OH or no substitution at position 3. Also, it was found that presence of 3′,4′-OCH3 on phenyl ring lead to increase in activity as compared to other substituents. Compound 24, a 7,8-benzoflavone derivative was found to be most potent being 50 times selective for BCRP and showing very low cytotoxicity at higher concentrations.
- Juvale, Kapil,Stefan, Katja,Wiese, Michael
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p. 115 - 126
(2013/10/01)
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- Isolation and synthesis of flavonols and comparison of their antioxidant activity
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Phytochemical investigation of the leaves of Astragalus beckari yielded four flavonol aglycones, namely kaempferol, quercetin, 5-deoxy kaempferol and fisitin. These isolated compounds were then synthesised in the laboratory using the Algar-Flyn-Oyamad reaction. Antioxidant activity of both the isolated and synthesised flavonoids was compared using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay method. The isolated flavonoids were found to be more active.
- Hasan, Aurangzeb,Sadiq,Abbas,Mughal,Khan, Khalid M.,Ali, Muhammad
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experimental part
p. 995 - 1003
(2010/09/05)
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- Structural basis for the activity of the RSK-specific inhibitor, SL0101
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Inappropriate activity of p90 ribosomal S6 kinase (RSK) has been implicated in various human cancers as well as other pathologies. We previously reported the isolation, characterization, and synthesis of the natural product kaempferol 3-O-(3″,4″-di-O-acetyl-α-l-rhamnopyranoside), termed SL0101 [Smith, J. A.; Poteet-Smith, C. E.; Xu, Y.; Errington, T. M.; Hecht, S. M.; Lannigan, D. A. Cancer Res., 2005, 65, 1027-1034: Xu, Y.-M; Smith, J. A.; Lannigan, D. A.; Hecht, S. M. Bioorg. Med. Chem., 2006, 14, 3974-3977: Maloney, D. J.; Hecht, S. M. Org. Lett., 2005, 7, 1097-1099]. SL0101 is a potent and specific inhibitor of RSK; therefore, we performed an analysis of the structural basis for the inhibitory activity of this lead compound. In in vitro kinase assays we found that acylation of the rhamnose moiety and the 4′, 5, and 7-hydroxyl groups are responsible for maintaining a high affinity interaction of RSK with SL0101. It is likely that the hydroxyl groups facilitate RSK binding through their ability to form hydrogen bonds. To determine whether the SL0101 derivatives were specific for inhibition of RSK we analyzed their ability to preferentially inhibit the growth of the human breast cancer line, MCF-7, compared to the normal human breast line, MCF-10A. We have previously validated this differential growth assay as a convenient readout for analyzing the specificity of RSK inhibitors [Smith, J. A.; Maloney, D. J.; Clark, D. E.; Xu, Y.-M.; Hecht, S. M.; Lannigan, D. A. Bioorg. Med. Chem., 2006, 14, 6034-6042]. We found that acylation of the rhamnose moiety was essential for maintaining the selectivity for RSK inhibition in intact cells. Further, the efficacy of SL0101 in intact cells is limited by cellular uptake as well as possible hydrolysis of the acetyl groups on the rhamnose moiety by ubiquitous intracellular esterases. These studies should facilitate the development of a RSK inhibitor, based on the SL0101 pharmacophore, as an anti-cancer chemotherapeutic agent.
- Smith, Jeffrey A.,Maloney, David J.,Hecht, Sidney M.,Lannigan, Deborah A.
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p. 5018 - 5034
(2008/03/12)
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- TWO FLAVONOL GLYCOSIDES FROM CHENOPODIUM AMBROSIOIDES
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Two new flavonol glycosides, kaempferol 3-rhamnoside-4'-xyloside and kaempferol 3-rhamnoside-7-xyloside along with kaempferol, isorhamnetin and quercetin have been identified from the fruits of Chenopodium ambrosioides.Their structures were established using spectroscopic and chemical evidence.
- Jain, Neeru,Alam, M. Sarwar,Kamil, M.,Ilyas, M.,Niwa, M.,Sakae, A.
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p. 3988 - 3991
(2007/10/02)
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- Studies of the Selective O-Alkylation and Dealkylation of Flavonoids. 10. Selective Demethylation of 7-Hydroxy-3,5,8-trimethoxyflavones with Anhydrous Aluminum Halide in Acetonitrile or Ether
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Demethylation of five 7-hydroxy-3,5,8-trimethoxyflavones and their acetates with anhydrous aluminum halides in acetonitrile or ether was studied and the following results were found. (1) The demethylation was apparently influenced by both solvents and afforded 5,7-dihydroxy-3,8-dimethoxyflavones in acetonitrile and 3,7-dihydroxy-5,8-dimethoxyflavones in ether as main products. (2) The demethylation with 5percent w/v anhydrous aluminum bromide in acetonitrile procedeed quantitatively to give a mixture of corresponding 5- and 3-hydroxyflavones, but that of 7-hydroxy-3,4',5,8-tetramethoxyflavone and its acetate with 10percent anhydrous aluminum chloride in acetonitrile afforded 6-acetyl-5,7-dihydroxy-3,4,8-trimethoxyflavone as a byproduct along with the 5- and 3-hydroxyflavones. (3) The demethylation of the acetates proceeded more smoothly than that of hydroxyflavones and was superior to that of the flavones with a hydroxy group. (4) These demethylations are available for the syntheses of 3- or 5-hydroxyflavones with no substituent at 6-position.
- Horie, Tokunaru,Tsukayama, Masao,Kawamura, Yasuhiko,Seno, Masamichi
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p. 4702 - 4709
(2007/10/02)
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- Studies on the Constituents of Apocynacae Plants. Gas Chromatography-Mass Spectrometric Determination of New Flavanoid Triglycosides from the Leaves of Cerbera manghas L.
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Two new flavonol triglycosides, named manghaslin(I) and clitorin(II), were isolated from the leaves of Cerbera manghas L. (Apocynaceae).The structures of I and II were elucidated as quertecin-3-O-L-rhamnosyl-(12)-O6)> D-glucoside(I) and kaempferol-3-O-L-rhamnosyl-(12)-O-6)> D-glucoside(II), respectively, by chemical and gas chromatography-mass spectrometric studies.Keywords-Cerbera manghas L.; Apocynaceae; flavonol triglycerides; manghaslin; clitorin; gas chromatography-mass spectrometry; photohydrolysis; mass spectrum; methanolysis.
- Sakushima, Akiyo,Hisada, Sueo,Ogihara, Yukio,Nishibe, Sansei
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p. 1219 - 1223
(2007/10/02)
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