- Flavonoid compound as well as synthesis method and application thereof
-
The invention relates to a semi-synthetic flavonoid compound and an anti-inflammatory application thereof. The invention belongs to the technical field of medicines, particularly relates to synthesis of derivatives of natural products and an application of the derivatives in the anti-inflammatory aspect, and more particularly relates to a synthesis method of flavonoid compounds and an application of the flavonoid compounds in the anti-inflammatory aspect. According to the method, hesperetin is taken as a raw material, flavonol aglycone is synthesized, and finally flavonoid glycoside is synthesized through debenzylation and acetyl reaction. According to the invention, 32 flavonoid compounds, including 14 flavonoid aglycones and 18 flavonoid glycosides, including 15 known compounds and 17 unreported compounds, are synthesized in total. The part of the compounds show good in-vitro anti-inflammatory activity and can become anti-inflammatory drugs or lead compounds.
- -
-
-
- 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
-
p. 13160 - 13176
(2020/11/23)
-
- Glucuronidation of Methylated Quercetin Derivatives: Chemical and Biochemical Approaches
-
Botanical supplements derived from grapes are functional in animal model systems for the amelioration of neurological conditions, including cognitive impairment. Rats fed with grape extracts accumulate 3′-O-methyl-quercetin-3-O-β-d-glucuronide (3) in their brains, suggesting 3 as a potential therapeutic agent. To develop methods for the synthesis of 3 and the related 4′-O-methyl-quercetin-7-O-β-d-glucuronide (4), 3-O-methyl-quercetin-3′-O-β-d-glucuronide (5), and 4′-O-methyl-quercetin-3′-O-β-d-glucuronide (6), which are not found in the brain, we have evaluated both enzymatic semisynthesis and full chemical synthetic approaches. Biocatalysis by mammalian UDP-glucuronosyltransferases generated multiple glucuronidated products from 4′-O-methylquercetin, and is not cost-effective. Chemical synthetic methods, on the other hand, provided good results; 3, 5, and 6 were obtained in six steps at 12, 18, and 30% overall yield, respectively, while 4 was synthesized in five steps at 34% overall yield. A mechanistic study on the unexpected regioselectivity observed in the quercetin glucuronide synthetic steps is also presented.
- Docampo-Palacios, Maite L.,Alvarez-Hernández, Anislay,Adiji, Olubu,Gamiotea-Turro, Daylin,Valerino-Diaz, Alexander B.,Viegas, Luís P.,Ndukwe, Ikenna E.,De Fátima, ?ngelo,Heiss, Christian,Azadi, Parastoo,Pasinetti, Giulio M.,Dixon, Richard A.
-
p. 14790 - 14807
(2020/12/23)
-
- Chemical structures of constituents from the leaves of Polyscias balfouriana
-
A new pyrrolidine derivative, (5S)-hydroxyethyl 2-oxopyrrolidine-5-carboxylate (1), a new flavonol glycoside, tamaraxetin 3,7-di-O-α-l-rhamnopyranoside (2), and a new triterpene saponin, polyscioside A methyl ester (3), along with six known compounds (4–9) were isolated from the leaves of Polyscias balfouriana. Their chemical structures were elucidated on the basis of extensive spectroscopic analysis.
- Sugimoto, Sachiko,Yamano, Yoshi,Khalil, Hany Ezzat,Otsuka, Hideaki,Kamel, Mohamed Salah,Matsunami, Katsuyoshi
-
p. 558 - 563
(2017/06/05)
-
- Effects of Functional Groups and Sugar Composition of Quercetin Derivatives on Their Radical Scavenging Properties
-
Quercetin derivatives are widespread in the plant kingdom and exhibit various biological actions. The aim of this study was to investigate the structure-activity relationships of quercetin derivatives, with a focus on the influence of functional groups and sugar composition on their antioxidant capacity. A series of quercetin derivatives were therefore prepared and assessed for their DPPH radical scavenging properties. Isoquercetin O-gallates were more potent radical scavengers than quercetin. The systematic analysis highlights the importance of the distribution of hydroxy substituents in isoquercetin O-gallates to their potency.
- Kato, Komei,Ninomiya, Masayuki,Tanaka, Kaori,Koketsu, Mamoru
-
p. 1808 - 1814
(2016/08/02)
-
- Synthesized quercetin derivatives stimulate melanogenesis in B16 melanoma cells by influencing the expression of melanin biosynthesis proteins MITF and p38 MAPK
-
In order to understand the effect of structure-activity relationships on melanogenesis using B16 melanoma cells, 19 quercetin derivatives were synthesized. Among the synthesized compounds, 3-O-methylquercetin (11) and 3′,4′,7-O-trimethylquercetin (14) increased melanin content more potently than the positive control theophylline, while exhibiting low cytotoxicity. Compound 11 exhibited less melanogenesis-stimulating activity than compound 14. However, 11 increased the expression of tyrosinase and tyrosinase-related protein 1 (TRP-1) to a greater extent than 14, thereby suggesting that melanogenesis in melanoma cells does not depend solely on the expression of the enzymes catalyzing melanin biosynthesis. Furthermore, 14 also stimulated the expression of the microphthalmia-associated transcription factor (MITF) and p-p38 mitogen activated protein kinase (MAPK), while they were not increased by 11. These results suggest that 11 may enhance the expression of tyrosinase and TRP-1 by regulating the proteasomal degradation of melanogenic enzymes and/or by activating other transcriptional factors regulating enzyme expression.
- Yamauchi, Kosei,Mitsunaga, Tohru,Inagaki, Mizuho,Suzuki, Tohru
-
p. 3331 - 3340
(2014/06/23)
-
- Biological evaluation and SAR analysis of O-methylated analogs of quercetin as inhibitors of cancer cell proliferation
-
Preclinical Research Using a high-throughout screening approach, the anticancer activities of 16 O-methylated (OMe) analogs of quercetin were assessed. The structure-activity relationships showed that OMe moieties at the 4′ and/or 7 positions were important for maintaining inhibitory activities against the 16 cancer cell lines. Furthermore, when the OH groups at the 3′ and 4′ positions were both replaced by OMe moieties, anticancer activity was enhanced.
- Shi, Zhi-Hao,Li, Nian-Guang,Tang, Yu-Ping,Shi, Qian-Ping,Tang, Hao,Li, Wei,Zhang, Xu,Fu, Hai-An,Duan, Jin-Ao
-
p. 455 - 462
(2015/04/14)
-
- Cytotoxic ellagitannins from Reaumuria vermiculata
-
Three ellagitannins and one disulfated flavonol were isolated from the aerial parts of Reaumuria vermiculata L. Besides that, 16 known compounds were characterized as well. The structures of all compounds were elucidated on the basis of spectroscopic data including 1D and 2D NMR and ESI HR-FTMS. The in vivo antioxidant activity using the oxygen radical absorbance capacity (ORAC) method, of the extract, its column fractions and two of the isolated ellagitannins was accomplished. In addition, a possible cytotoxicity of the extract and two of the new ellagitannins on HaCaT human keratinocytes and the activity of both compounds against the prostate cancer cell line (PC-3) were also assessed, whereby a potent cytotoxicity with IC50 less than 1 μg/ml was determined for both compounds. Besides, the extract exhibited a potential cytotoxic effect against four different solid tumor cell lines, namely liver (Huh-7), colorectal (HCT-116), breast (MCF-7) and prostate (PC-3). The IC50s were found to be substantially low (ranged from 1.3 ± 0.15 to 2.4 ± 0.22 μg/ml) with relatively low resistance possibility reaching to 0% in the case of Huh-7 cell.
- Nawwar, Mahmoud A.,El-Rai, Mohamed A.,Ayoub, Nahla A.,Bassyouny, Fatma,Mostafa, Eman S.,Al-Abd, Ahmed M.,Harms, Manuela,Wende, Kristian,Lindequist, Ulrike,Linscheid, Michael W.
-
p. 1256 - 1266,11
(2020/07/31)
-
- Metabolism-based synthesis, biologic evaluation and SARs analysis of O-methylated analogs of quercetin as thrombin inhibitors
-
In blood, quercetin is mainly found in metabolized forms. In order to study the activities of these quercetin metabolites in cardiovascular disease, 17 methylquercetin derivatives were synthesized based on metabolism in vivo, their thrombin inhibition activity were evaluated through the analyzation of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen (FIB). The results showed that 6 methylquercetin derivatives had stronger inhibitory activities than that of quercetin. Preliminary SARs analysis showed that hydroxyl groups at C-3′ and C-4′ position in the B-ring and hydroxyl group at C-3 position in the C-ring played key roles in the thrombin inhibitory activity. The findings of this study would provide information for the exploitation and utilization of quercetin as thrombin inhibitor for thrombotic disease treatment.
- Shi, Zhi-Hao,Li, Nian-Guang,Tang, Yu-Ping,Wei-Li,Lian-Yin,Yang, Jian-Ping,Hao-Tang,Duan, Jin-Ao
-
p. 210 - 222
(2012/09/07)
-
- Synthesis and antioxygenic activities of seabuckthorn flavone-3-ols and analogs
-
A practical synthesis of polyhydroxy- and regiospecifically methylated flavone-3-ols which are components of commercial 'seabuckthorn flavone' has been achieved by modified Algar-Flynn-Oyamada method. Antioxidant activities of seabuckthorn extracts, isolated products and a number of flavone-3-ols have been determined. Structure-activity relationships have been discussed. Amongst the compounds tested, gallic acid, which is also present in seabuckthorn, was found to be the most effective antioxidant and radioprotectant.
- Pandurangan,Bose, Chinchu,Banerji
-
experimental part
p. 5328 - 5330
(2011/10/09)
-
- Selective monomethylation of quercetin
-
Quercetin was monomethylated under mild conditions in moderate yields through selective deprotection. The combined effects of the protecting group and the heating mode on the reactivity were investigated. The presence of borax and the use of microwave irradiation significantly improved the yield and selectivity of alkylation. Georg Thieme Verlag Stuttgart - New York.
- Zhou, Zhong-Hua,Fang, Zhuan,Jin, Hui,Chen, Yue,He, Ling
-
experimental part
p. 3980 - 3986
(2011/02/22)
-
- Semisynthesis of natural flavones inhibiting tubulin polymerization, from hesperidin
-
Semisynthesis of 5,3'-dihydroxy-3,6,7,8,4'-pentamethoxyflavone (1), a natural flavone that binds with high affinity to tubulin, was performed from hesperidin, the very abundant Citrus flavanone, by a five-step sequence. The last step of the synthesis also gave rise to 5,3'-dihydroxy-3,6,7,4'- tetramethoxyflavone (= casticin or vitexicarpin) (10), 5,3'-dihydroxy-3,7,8,4'- tetramethoxyflavone (= gossypetin 3,7,8,4'-tetramethyl ether) (11), and, unexpectedly, 5,7,3'-trihydroxy-3,6,8,4'-tetramethoxyflavone (12) and 5,3'-dihydroxy-8-dimethylamino-3,6,7,4'-tetramethoxyflavone (= 8-dimethylaminocasticin) (13). Cytotoxicity and antitubulin activity of these five flavones, as well as 5,3'-dihydroxy-3,7,4'-trimethoxyflavone (= ayanin) (14) and intermediate 6,8-dibromo-ayanin (8), were evaluated. Comparison of the responses confirmed and clarified the influence of the A-ring substitution pattern on the biological activity.
- Lewin, Guy,MacIuk, Alexandre,Thoret, Sylviane,Aubert, Genevieve,Dubois, Joelle,Cresteil, Thierry
-
experimental part
p. 702 - 706
(2010/08/22)
-
- Aphyllin, the first isoferulic acid glycoside and other phenolics from Tamarix aphylla flowers
-
The first glycosylated isoferulic acid, isoferulic acid 3-O-β-glucopyranoside, together with the new phenolics, tamarixetin 3,3′-di-sodium sulphate and dehydrodigallic acid dimetyl ester have been characterized from a flower extract of Tamarix aphylla. Th
- Nawwar, Mahmoud A. M.,Hussein,Ayoub,Hofmann,Linscheid,Harms,Wende,Lindequist
-
body text
p. 342 - 347
(2010/07/10)
-
- An efficient partial synthesis of 4'-O-methylquercetin via regioselective protection and alkylation of quercetin
-
An efficient partial 5-step synthesis of 4'-O-methylquercetin from quercetin in 63% yield is reported. This strategy relies on the selective protection of the catechol group with dichlorodiphenylmethane in diphenyl ether as solvent and on the selective pr
- Li, Nian-Guang,Tang, Yu-Ping,Yang, Jian-Ping,Duan, Jin-Ao,Shi, Zhi-Hao
-
experimental part
(2010/04/22)
-
- Flavonoid glycosides from Astragalus galegiformis leaves
-
New flavonoid oligosides, the structures of which were established by chemical transformations and UV, IR, PMR, and 13C NMR spectra, were isolated from Astragalus galegiformis leaves.
- Alaniya,Kavtaradze,Bassarello,Skhirtladze,Pizza,Kutateladze
-
p. 681 - 685
(2008/02/08)
-
- Hemisynthesis of all the O-monomethylated analogues of quercetin including the major metabolites, through selective protection of phenolic functions
-
A new methodology for the hemisynthesis of all the five O-monomethylated analogues of quercetin (3′-O-methylquercetin (isorhamnetin), 4′-O-methylquercetin (tamarixetin), 3-O-methylquercetin, 5-O-methylquercetin (azaleatin) and 7-O-methylquercetin (rhamnetin)) through sequential protection of the different phenolic functions of quercetin is reported.
- Bouktaib, Mohamed,Lebrun, Stéphane,Atmani, Aziz,Rolando, Christian
-
p. 10001 - 10009
(2007/10/03)
-
- Structural requirements of flavonoids and related compounds for aldose reductase inhibitory activity
-
The methanolic extracts of several natural medicines and medicinal foodstuffs were found to show an inhibitory effect on rat lens aldose reductase. In most cases, flavonoids were isolated as the active constituents by bioassay-guided separation, and among them, quercitrin (IC50=0.15 μM), guaijaverin (0.18 μM), and desmanthin-1 (0.082 μM) exhibited potent inhibitory activity. Desmanthin-1 showed the most potent activity, which was equivalent to that of a commercial synthetic aldose reductase inhibitor, epalrestat (0.072 μM). In order to clarify the structural requirements of flavonoids for aldose reductase inhibitory activity, various flavonoids and related compounds were examined. The results suggested the following structural requirements of flavonoid: 1) the flavones and flavonols having the 7-hydroxyl and/or catechol moiety at the B ring (the 3′,4′-dihydroxyl moiety) exhibit the strong activity; 2) the 5-hydroxyl moiety does not affect the activity; 3) the 3-hydroxyl and 7-O-glucosyl moieties reduce the activity; 4) the 2-3 double bond enhances the activity; 5) the flavones and flavonols having the catechol moiety at the B ring exhibit stronger activity than those having the pyrogallol moiety (the 3′,4′,5′-trihydroxyl moiety).
- Matsuda, Hisashi,Morikawa, Toshio,Toguchida, Iwao,Yoshikawa, Masayuki
-
p. 788 - 795
(2007/10/03)
-
- Flavonol glycosides from Costus spicatus
-
Two flavonol diglycosides, tamarixetin 3-O-neohesperidoside, kaempferide 3-O-neohesperidoside and the known quercetin 3-O-neohesperidoside, together with six other known flavonoids were isolated from the leaves of Costus spicatus and their structures were elucidated by a combination of spectroscopic and chemical methods. The flavonol diglycosides were evaluated for inhibitory activity of nitric oxide production by activated macrophages (Fig. 1).
- Da Silva, Bernadete P.,Bernardo, Robson R.,Parente, Jose P.
-
-
- O-methylation of flavonoids by cell-free extracts of calamondin orange
-
Cell-free extracts of calamondin orange (Citrus mitis) catalysed the O-methylation of almost all hydroxyls of a number of flavonoids, indicating the existence in citrus tissues of ortho, meta, para and 3-O-methyltransferases. The latter, hitherto unreported enzyme, catalysed the formation of 3-O-methyl ethers of galangin and quercetin. The stepwise O-methylation of a number of compounds, especially quercetin and quercetagetin, tends to suggest a coordinated sequence of O-methylations on the surface of a multienzyme complex. The methyl acceptor abilities of the flavonoid substrates used are discussed in relation to their hydroxyl substitution patterns and their negative electron density distribution.
- Brunet, Gunter,Ibrahim, Ragai K.
-
p. 741 - 746
(2007/10/02)
-
