cas 529-53-3, SCUTELLAREIN | Articles data

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Gumenyuk
(1975)
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Jay,Gonnet
p. 953
(1973)
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Synthesis and protective effect of scutellarein on focal cerebral ischemia/reperfusion in rats
Scutellarein, the main metabolite of scutellarin in vivo, has relatively better solubility, bioavailability and bio-activity than scutellarin. However, compared with scutellarin, it is very difficult to obtain scutellarein from Nature. Therefore, the present study focused on establishing an efficient route for the synthesis of scutellarein by hydrolyzing scutellarin. Neurological deficit score and cerebral infarction volume with the administration of scutellarein were then used to compare its neuroprotective effects on focal cerebral ischemia/reperfusion in rats induced by middle cerebral artery occlusion (MCAO) with those of scutellarin. The results showed that scutellarein had better protective effect on focal cerebral ischemia/reperfusion than scutellarin, which laid the foundation for further research and development of scutellarein as a promising candidate for ischemic cerebro-vascular disease.
Qian, Lihua,Shen, Minzhe,Tang, Hao,Tang, Yuping,Zhang, Li,Fu, Yifan,Shi, Qianping,Li, Nian-Guang
p. 10667 - 10674,8
(2012)
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Sheremet,Komissarenko
(1971)
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Synthesis and Bioactivity Characterization of Scutellarein Sulfonated Derivative
Scutellarin (1) has been widely used to treat acute cerebral infarction in clinic, but poor aqueous solubility decreases its bioavailability. Interestingly, scutellarin (1) could be metabolized into scutellarein (2) in vivo. In this study, a sulfonic group was introduced at position C-8 of scutellarein (2) to enhance the aqueous solubility of the obtained derivative (3). DPPH (1,1-diphenyl-2-picrylhydrazyl)-radical scavenging ability and antithrombic activity were also conducted to determine its bioactivity. The result showed that scutellarein derivate (3) could be a better agent for ischemic cerebrovascular disease treatment.
Gu, Ting,Zhong, Yue,Lu, Yu-Ting,Sun, Ying,Dong, Ze-Xi,Wu, Wen-Yu,Shi, Zhi-Hao,Li, Nian-Guang,Xue, Xin,Fang, Fang,Li, He-Min,Tang, Yu-Ping
(2017)
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Gritsenko,Litvinenko
(1969)
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Bandyukova,Khalmatov
(1967)
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Bandyukova,Boikova
(1969)
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Organic synthesis method of scutellarein
The invention provides an organic synthesis method of scutellarein, wherein the organic synthesis method comprises the following steps: 1) by using p-methoxycinnamic acid as a raw material, synthesizing p-methoxycinnamoyl chloride under the catalytic action of an acyl chloride reagent and a catalyst; step 2) carrying out esterification reaction on p-methoxycinnamoyl chloride and 3,4,5-trimethoxyphenol under the action of Lewis acid, and then carrying out Fries rearrangement, so as to obtain 9-hydroxy-5,6,7,4'-tetramethoxychalcone; step 3) performing intramolecular cyclization on the 9-hydroxy-5,6,7,4'-tetramethoxychalcone under the action of an oxidizing agent to obtain 5,6,7,4'-tetramethoxyflavone; and step 4) demethylating the 5,6,7,4'-tetramethoxyflavone under the protection of N2 underthe action of a demethylating reagent to generate scutellarin. As the reaction operation is simple and safe, the post-treatment operation is easy, and the yield is high, the method has a wide industrial application prospect.
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(2020/07/12)

Benzoic acid nitrogen mustard fragment-containing compound and preparation method and use thereof
The invention relates to the field of natural medicine and medicine chemistry, and particularly relates to a compound containing benzoic acid nitrogen mustard fragment and a preparation process and use, in particular to a compound which introduces a benzoic acid nitrogen mustard fragment at a 4'-OH through a linking group after derivatization of the 6, 7-position of scutellarin, and a pharmaceutically acceptable salt thereof. The method also relates to the preparation process and antitumor activity of these compounds. The method of the benzoic acid nitrogen mustard fragment-containing compoundis shown in the general formula I, wherein m, n are as described in the claims and the specification. The formula is shown in the description.
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Paragraph 0016; 0024-0026

(2019/01/23)

Synthesis and biological evaluation of scutellarein alkyl derivatives as preventing neurodegenerative agents with improved lipid soluble properties
Background: Exogenous antioxidants are considered as a promising therapeutic approach to treat neurodegenerative diseases since they could prevent and/or minimize the neuronal damage by oxidation. Objective: Three series of lipophilic compounds structurally based on scutellarein (2), which is one metabolite of scutellarin (1) in vivo, have been designed and synthesized. Methods: Their antioxidant activity was evaluated by detecting the 2-thiobarbituric acid reactive substance (TBARS) produced in the ferrous salt/ascorbate-induced autoxidation of lipids, which were present in microsomal membranes of rat hepatocytes. The lipophilicity of these compounds indicated as partition coefficient between n-octanol and buffer was investigated by ultraviolet (UV) spectrophotometer. Results: This study indicated that compound 5e which had a benzyl group substituted at the C4'-OH position showed a potent antioxidant activity and good lipophilicity. Conclusion: 5e could be an effective candidate for preventing or reducing the oxidative status associated with the neurodegenerative processes.
Li, He-Min,Gu, Ting,Wu, Wen-Yu,Yu, Shao-Peng,Fan, Tian-Yuan,Zhong, Yue,Li, Nian-Guang
p. 771 - 780
(2019/11/02)

Flavone Glucosides from the Aerial Part of Scutellaria comosa
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Karimov,Ostroushko, Yu. V.,Botirov, E. Kh.
p. 545 - 546
(2019/07/02)

Scaffold hopping strategy for the design, synthesis and biological activity evaluation of novel hexacyclic scutellarein derivatives with a 1,3-oxazine ring fused at A-ring
Background: Discovery of novel agents with anticoagulant and antioxidant activity is very important to treat cerebrovascular disease. Lead compound LR3d discovered in our laboratory exhibited stronger anticoagulant ability and good antioxidant activity, compared with scutellarein (2), which is the major in vivo active metabolite of the natural product scutellarin (1). Objective: Design and synthesis novel scutellarein derivatives with improved anticoagulant and antioxidant activity. Methods: By utilizing a scaffold hopping strategy on LR3d, we describe the design and synthesis of a series of novel hexacyclic scutellarein derivatives 4 with a 1,3-oxazine ring fused at positions 7 and 8 in A ring. The thrombin inhibitory activities of all these new compounds were studied by the analysis of thrombin time (TT), activated partial thromboplastin time (APTT), prothrombin time (PT) and fibrinogen (FIB). The antioxidant abilities of these analogs were evaluated by using 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) method through 1,1- diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH) assay. Results: Nine new hexacyclic scutellarein derivatives with a 1,3-oxazine ring fused at A-ring were synthesized, the results of the biological activity evaluation showed that compound 4e exhibited stronger anticoagulant and antioxidant ability compared to LR3d. Conclusion: 4e could be used for further development to treat ischemic cerebrovascular disease.
Zhong, Yue,Lu, Yu-Ting,Sun, Ying,Li, Nian-Guang,Gu, Ting,Wu, Wen-Yu,Yu, Shao-Peng,Shi, Zhi-Hao
p. 478 - 484
(2018/07/25)

Scutellarin aglycone nitrogen mustard derivative and preparation method and application thereof
The invention belongs to the field of natural medicine and medicinal chemistry and relates to a scutellarin aglycone nitrogen mustard derivative and a preparation method and application thereof, in particular to a scutellarin aglycone nitrogen mustard derivative of which 4'-OH is combined with benzoic acid nitrogen mustard and a preparation method and antitumor activity thereof. The structure of the scutellarin aglycone nitrogen mustard derivative and pharmaceutically acceptable salt thereof is as shown in the general formula I, wherein R and n are as described in claims and the specification.The formula I is shown in the description.
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Paragraph 0029-0031

(2018/12/14)

Synthesis of scutellarein derivatives with antiproliferative activity and selectivity through the intrinsic pathway
To explore antitumor agents with potent efficacy and low toxicity, scutellarein derivatives with benzoic acid mustard (10a?c, 11a?c and 13a?c) were designed and synthesized. The antiproliferative activities of the target derivatives against A549, MCF-7 and Bel-7402 cancer cell lines were tested. Compound 10a showed the strongest potency with an IC50 value of 1.50 μM against MCF-7 cell line, and displayed low toxicity against human liver L-O2 normal cells (IC50 > 50 μM), showing specificity between normal and malignant cells. The mechanism studies revealed that 10a could induce apoptosis in MCF-7 cells, arrest MCF-7 cell cycle at the G1 phase and cause mitochondrial dysfunction in a concentration-dependant manner. Furthermore, the enhanced expression of the pro-apoptotic proteins caspase-9, caspase-3, Bax and cytochrome c, and the reduced expression of the anti-apoptotic protein Bcl-2 confirmed that 10a induced the intrinsic apoptosis pathway in MCF-7 cells. The potent antiproliferative activity and good selectivity guaranteed 10a a lead compound for the further development into anticancer therapeutics, especially for breast cancer.
Han, Tong,Wang, Yan,Wang, Mingying,Li, Xu,Cheng, Keguang,Gao, Xiang,Li, Zhanlin,Bai, Jiao,Hua, Huiming,Li, Dahong
p. 493 - 501
(2018/09/25)

Synthesis method of scutellarein
The invention provides a synthesis method of scutellarein, aiming at solving the problems in the prior art that the yield of chemically synthesized scutellarein is relatively low and a dangerous reagent is used in a synthesis process. The synthesis method comprises the following steps: step 1) taking ethyl acetoacetate and p-anisoyl chloride as raw materials and synthesizing ethyl 3-(4-methoxyphenyl)-3-oxopropanoateethyl p-anisoyl acetate; step 2) synthesizing 5,6,7,4'-tetramethoxy flavone through the ethyl 3-(4-methoxyphenyl)-3-oxopropanoateethyl p-anisoyl acetate and 3,4,5-trimethoyphenol; step 3) removing methyl from the 5,6,7,4'-tetramethoxy flavone to obtain a scutellarein crude product; step 4) purifying the scutellarein crude product to finally obtaining a high-content scutellareinrefined product.
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(2019/01/08)

An efficient, scalable approach to hydrolyze flavonoid glucuronides via activation of glycoside bond
Hydrolyzing flavonoid glucuronides into corresponding aglycones posed some significant challenges. To improve acid-catalyzed hydrolysis process of flavonoid glucuronide, structures of glucuronide, hydrolysis parameters and post-processing were optimized. The optimized condition was performed by hydrolysis flavonoid glycoside methyl ester in a mixed solvent consisting of 2?mol/L H2SO4/EtOH/H2O (1/8/1, v/v/v) at 95?°C for 7?h and resulted in up to 90% aglycone yields, minimal byproduct formations and milder hydrolysis conditions. Furthermore, the optimized method avoids tedious purification steps and is easily conducted on a relatively large-scale using economical and commercially available reagents.
Jiang, Xue-Yang,Li, Xin-Chen,Liu, Wen-Yuan,Xu, Yun-Hui,Feng, Feng,Qu, Wei
p. 1895 - 1903
(2017/03/11)

The invention relates to a raw material for preparing the glucuronic acid the glucoside is corresponding aglycone (by machine translation)
The invention discloses a glucuronic acid the glucoside is raw material for preparing the corresponding aglycone method, comprises the following steps: (1), synthesis of methyl chlorine sulfurous acid; (2), glucuronic acid methyl ester glucoside synthesis; (3), the inorganic acid is added in the ethanol, into inorganic acid ethanol solution, and then the inorganic acid ethanol solution is added to step (2) is made in the product of the glucuronic acid methyl ester glucoside, acid hydrolysis; (4), after the reaction, the reaction is cooled down to the room temperature after the, in the reaction liquid is poured into the water, standing precipitate, precipitation after complete filtering, the resulting solid for recrystallization dilute alcohol, obtaining the corresponding aglycone pure product. The method of the invention essentially solves the problem of the glucuronic acid the glucoside is difficult hydrolysis, the process is simple, short reaction time, does not need to use a large amount of organic solvent, after treatment is simple, the resulting aglycone yield is as high as 90%, purity as high as 99%, low cost, can be used for large-scale industrial production. (by machine translation)
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Paragraph 0063; 0064; 0068; 0069; 0073; 0074; 0075-0077

(2017/09/23)

A practical synthesis of the flavone, scutellarein
A practical and economical five-step synthesis of the flavone scutellarein has been achieved in 60% overall yield using the available and cheap 2,6-dimethoxy-1,4-benzoquinone as starting material. The reaction sequence involved reduction to the corresponding quinol, Friedel-Crafts acetylation, Claisen-Schmidt condensation with p-methoxybenzaldehyde, cyclisation and demethylation. The procedure is operationally simple and amenable to scale-up synthesis.
Wang, Qian,Liao, Xia-Li,Xiang, Cheng,Yang, Jian
p. 157 - 159
(2017/03/27)

An efficient chemical synthesis of scutellarein: An in vivo metabolite of scutellarin
Scutellarein (2), which is an important in vivo metabolite of scutellarin (1), was synthesized from 3,4,5-trimethoxyphenol (3) in high yield in four steps. This strategy relies on acetylation, aldolization, cyclization and hydrolysis reactions, respectively.
Dong, Ze-Xi,Li, Nian-Guang,Zhang, Peng-Xuan,Gu, Ting,Wu, Wen-Yu,Shi, Zhi-Hao,McPhee, Derek J.,Dehaen, Wim
(2016/04/26)

Method for preparing scutellarin
The invention relates to a method for preparing scutellarin. According to the method, the scutellarin can be efficiently prepared from 2,6-dimethoxy benzoquinone as a starting raw material through five reactions of reduction, Friedel-Crafts acetylation, Claisen condensation, dehydrogenation oxidation cyclization and demethylation. The starting raw material and a reagent are cheap and easily available, synthetic steps are few, the operation is simple and convenient, the production control is simple, the product yield is high, and the purity is high. The method is applicable to large-scale preparation and production application of the scutellarin.
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Paragraph 0013

(2017/01/02)

A 6-methyl Scutellarin arctigenin method for the preparation of (by machine translation)
The invention relates to the field of chemical synthesis, in particular to Chinese traditional medicine molecule Scutellarin active metabolite of preparation, the ponicidin breviscapine under the action of the strong acid hydrolysis glucuro molecules are the 4 [...], 5, 6, 7? Four hydroxy flavone, the 4 [...], 5, 6, 7? Four hydroxy flavone with bromo the presence of the acid-binding agent, generating 5,6? Dihydroxybenzonic? 4 the [...], 7? B benzyloxy flavone, then in alkaline conditions with iodomethane reaction generating 5? Hydroxy? 6? Methoxy? 4 the [...], 7? B benzyloxy flavone, the final 5? Hydroxy? 6? Methoxy? 4 the [...], 7? B benzyloxy-flavone in palladium carbon catalytic hydrogenation by debenzylation in the presence of 6? Methyl Scutellarin aglycon. The step of this invention is simple, is easy to be purified, mild condition, low cost, overall reaction yield is greater than 70%, the synthetic product has high purity, greater than 99.0%, suitable for technical production. (by machine translation)
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Paragraph 0031 - 0033

(2017/04/06)

Design, Synthesis, and Biological Evaluation of Scutellarein Derivatives Based on Scutellarin Metabolic Mechanism in Vivo
Three series of scutellarein derivatives have been designed and synthesized based on metabolic mechanism of scutellarin (1) in vivo. Their thrombin inhibition activities were tested through the analyzation of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB). The antioxidant activities of these target products were assessed by 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay and the ability to protect PC12 cells against H2O2-induced cytotoxicity, and their solubilities were evaluated by ultraviolet (UV) spectrophotometer. The results showed that the two isopropyl groups substituted derivative (18c) demonstrated stronger anticoagulant activity, better water solubility, and good antioxidant activity compared with scutellarein (2), which warrants further development of 18c as a promising agent for ischemic cerebrovascular disease treatment. Three series of scutellarein derivatives have been designed and synthesized based on metabolic mechanism of scutellarin (1) in vivo. The results of the biological evaluation showed that the two isopropyl groups substituted derivative (18c) demonstrated stronger anticoagulant activity, better water solubility, and good antioxidant activity compared with scutellarein (2), which warrants further development of 18c as a promising agent for ischemic cerebrovascular disease treatment.
Dong, Ze-Xi,Shi, Zhi-Hao,Li, Nian-Guang,Zhang, Wei,Gu, Ting,Zhang, Peng-Xuan,Wu, Wen-Yu,Tang, Yu-Ping,Fang, Fang,Xue, Xin,Li, He-Min,Cheng, Hai-Bo,Yang, Jian-Ping,Duan, Jin-Ao
p. 946 - 957
(2016/05/24)

Permeability of novel 4′-N-substituted (aminomethyl) benzoate-7-substituted nicotinic acid ester derivatives of scutellarein in Caco-2 cells and in an in vitro model of the blood-brain barrier
A series of 4′-N-substituted (aminomethyl) benzoate-7-substituted nicotinic acid ester derivatives of scutellarein was designed and synthesized. Evaluation of physiochemical properties showed that the newly designed compounds had greater chemical stability and aqueous solubility than scutellarin or scutellarein. The permeabilities (Papp AP to BL) of compounds 7b and 7e in Caco-2 cells were 5.9-fold and 3.7-fold higher than that of scutellarin, and 3.7-fold and 2.4-fold higher than that of scutellarein. The permeabilities (Papp AP to BL) of compounds 7b and 7e in an in vitro model of the blood–brain barrier were 9.7-fold and 5.9-fold higher than that of scutellarin, and 9.2-fold and 5.6-fold higher than that of scutellarein.
Ou, Yu,Luo, Min,Dong, Yong-Xi,Su, Hang,Fu, Xiao-Zhong,Cha, Yu-Feng,Zhang, Shun,Zhao, Yong-Long,Li, Yong-Jun,Wang, Yong-Lin
p. 2205 - 2213
(2016/10/25)

METHOD FOR PREPARING HIGH PURITY SCUTELLARIN AGLYCONE
Provided is a method for preparing scutellarin aglycone. In the method, 5,6,7,4'-tetramethoxy flavone is used as raw material, and high purity scutellarin aglycone is obtained through four steps of demethylation, acylation, hydrolyzation, and refinement. The preparing method is characterized by a low synthesis cost, a short line, and a high reaction yield, and the product is easily purified, can implement industrialized production, and has a desired industrial application prospect.
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Paragraph 0023

(2015/05/19)

Application of N-substituted (aminomethyl)benzoate strategy in design of scutellarein derivatives with improved Caco-2 cell permeability and in vitro antioxidative activity
A series of 4′-N-substituted (aminomethyl)benzoate derivatives of scutellarein were designed and synthesized. Evaluation of their physiochemical properties showed that the designed target compounds 5a-e exhibit higher chemical stability and aqueous solubility than scutellarin and scutellarein. The permeability (Papp AP to BL) of 5c-e in Caco-2 cells were 2.8, 8.1, and 12.6 times higher than that of scutellarin and 1.3, 4.1, and 6.0 times higher than that of scutellarein; especially, 5e had the highest Papp AP to BL value (7.19 ± 0.31 × 10-6 cm/s) and the lowest ER (Papp BL to AP/Papp AP to BL) value of 0.17. In vitro antioxidative evaluation results revealed that 5e could protect against H2O2-induced PC12 cells' oxidative damage by attenuating mitochondrial membrane potential loss and decreasing H2O2-induced reactive oxygen species (ROS) production.
Dai, Ze-Qin,Su, Hang,Luo, Min,Ou, Yu,Fu, Xiao-Zhong,Dong, Yong-Xi,Cha, Yu-Feng,Zhang, Shun,Huang, Yong,Wang, Yong-Lin
p. 1959 - 1965
(2015/08/24)

Synthesis and biological evaluation of methylated scutellarein analogs based on metabolic mechanism of scutellarin in vivo
Scutellarin (1) could be hydrolyzed into scutellarein (2) in vivo and then converted into methylated, sulfated and glucuronidated forms. In order to investigate the biological activities of these methylated metabolites, eight methylated analogs of scutellarein (2) were synthesized via semi-synthetic methods. The antithrombotic activities of these compounds were evaluated through the analyzation of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen (FIB). Their antioxidant activities were assessed by measuring their scavenging capacities toward 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and the ability to protect PC12 cells against H2O2-induced cytotoxicity. Furthermore, the physicochemical properties of these compounds including aqueous solubility and lipophilicity were also investigated. The results showed that 6-O-methylscutellarein (5) demonstrated potent antithrombotic activity, stronger antioxidant activity and balanced solubility and permeability compared with scutellarin (1), which warrants further development of 5 as a promising lead for the treatment of ischemic cerebrovascular disease.
Shi, Zhi-Hao,Li, Nian-Guang,Wang, Zhen-Jiang,Tang, Yu-Ping,Dong, Ze-Xi,Zhang, Wei,Zhang, Peng-Xuan,Gu, Ting,Wu, Wen-Yu,Yang, Jian-Ping,Duan, Jin-Ao
p. 95 - 105
(2015/11/10)

Synthesis of scutellarein derivatives to increase biological activity and water solubility
In order to improve the biological activity and water solubility of scutellarin (1), some derivatives of its main metabolite (scutellarein) were designed and synthesized. All the compounds were tested for their thrombin inhibition activity through the analyzation of thrombin time (TT), activated partial thromboplastin time (APTT), prothrombin time (PT) and fibrinogen (FIB). Their antioxidant activities were assessed by measuring their scavenging capacities toward 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and the ability to protect PC12 cells against H2O2-induced cytotoxicity, their water solubility were also assessed by ultraviolet (UV) spectrophotometer. The results showed that compound 8b demonstrated stronger anticoagulant and antioxidant activity, better water solubility compared with scutellarein (2), which warrants it as a promising agent for the treatment of ischemic cerebrovascular disease.
Shi, Zhi-Hao,Li, Nian-Guang,Shi, Qian-Ping,Zhang, Wei,Dong, Ze-Xi,Tang, Yu-Ping,Zhang, Peng-Xuan,Gu, Ting,Wu, Wen-Yu,Fang, Fang,Xin-Xue,Li, He-Min,Yang, Jian-Ping,Duan, Jin-Ao
p. 6875 - 6884
(2015/11/11)

An improved synthesis of 6-o-methyl-scutellarein through selective benzylation
An improved synthesis of 6-O-methyl-scutellarein is described. Benzyl bromide was selected to protect both the hydroxyl groups at C-4'and C-7 in scutellarein. The product was then methylated and deprotected to produce the target compound in high yield in four steps.
Zhang, Wei,Dong, Ze-Xi,Gu, Ting,Li, Nian-Guang,Wu, Wen-Yu,Zhang, Peng-Xuan,Tang, Yu-Ping,Yang, Jian-Ping,Xue, Xin,Fang, Fang,Li, He-Min,Cheng, Hai-Bo,Duan, Jin-Ao,Shi, Zhi-Hao
p. 674 - 676
(2016/01/25)

A new and efficient synthesis of 6-O-methylscutellarein, the major metabolite of the natural medicine scutellarin
In this paper, a new and efficient synthesis of 6-O-methylscutellarein (3), the major metabolite of the natural medicine scutellarin, is reported. Two hydroxyl groups at C-4′ and C-7 in 2 were selectively protected by chloromethyl methyl ether after the reaction conditions were optimized, then 6-O-methyl-scutellarein (3) was produced in high yield after methylation of the hydroxyl group at C-6 and subsequent deprotection of the two methyl ether groups.
Zhang, Wei,Dong, Ze-Xi,Gu, Ting,Li, Nian-Guang,Zhang, Peng-Xuan,Wu, Wen-Yu,Yu, Shao-Peng,Tang, Yu-Ping,Yang, Jian-Ping,Shi, Zhi-Hao
p. 10184 - 10191
(2015/08/06)

Efficient chemical synthesis of a scutellarein derivative containing morpholine ring
Scutellarin (1) [5,6-dihydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-1-benzopyran-7- yl β-D-glucopyranosiduronic acid] is very effective in the clinical treatment of cerebral infarction and coronary heart disease in China. Pharmacokinetic studies showed that scutellarin (1) is readily metabolized to scutellarein (2) [5,6,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one] in the intestine by β-glucuronide enzyme prior to absorption. In order to improve the biological activity of scutellarin (1), our group has previously synthesized many scutellarin derivatives based on their in vivo metabolic mechanism. The results showed that morpholine ring substituted at C-7 or C-8 position induced better antioxidant activity, water solubility and anticoagulant activity compared to scutellarin (1). In this paper, an efficient synthetic method for the construction of 5,6,7-trihydroxy-2-[4-[2-(4-morpholinyl)ethoxy] phenyl]-4H-1-benzopyran-4-one (5) is reported. This synthetic route will facilitate the synthesis of scutellarein derivatives containing an amine side chain at the C-4′ position.
Shi, Qian-Ping,Shi, Zhi-Hao,Li, Nian-Guang,Tang, Yu-Ping,Hao-Tang,Zhang, Wei,Shen, Min-Zhe,Dong, Ze-Xi,Zhang, Peng-Xuan,Yang, Jian-Ping,Duan, Jin-Ao
p. 590 - 595
(2014/07/21)

Hydrolysis of scutellarin and related glycosides to scutellarein and the corresponding aglycones
Scutellarein has been prepared by the hydrolysis of scutellarin with sulfuric acid to provide this biologically important rare flavone in up to > 90% yield and on the 5 g scale in minutes. This protocol has been applied to five other flavonoid glycosides (rutin, hesperidin, naringin, baicalin and diosmin) which are readily hydrolysed to their corresponding aglycones.
Zhang, Wei,Yi, Dong,Gao, Kai,Liu, Manshuo,Yang, Jian,Liao, Xiali,Yang, Bo
p. 396 - 398
(2014/08/05)

An improved synthesis of scutellarin-7-O-glucuronid
An eight-step synthesis of scutellarin-7-O-glucuronide via a novel preparation of the intermediate 5,6,7,4′-trimethoxyflavone from a chalcone derivative is described. The conditions of certain steps were studied and optimised to give an overall yield of 20%.
Chen, Duo-Zhi,Wu, Ting,Zhao, Zhao,Lin, Xi-Quan,Yang, Tao,Yang, Jian
p. 671 - 673
(2014/01/17)

Design, synthesis and biological evaluation of glucose-containing scutellarein derivatives as neuroprotective agents based on metabolic mechanism of scutellarin in vivo
Based on metabolic mechanism of scutellarin in vivo that scutellarin could be hydrolyzed into scutellarein by β-glucuronide enzyme, some glucose-containing scutellarein derivatives were designed and synthesized through the introduction of glucose moiety at C-7 position of scutellarein via a glucosidic bond. Biological activity evaluation showed that these glucose-containing scutellarein derivatives exhibited potent DPPH radical scavenging activities. Furthermore, the improvement of physicochemical properties such as anticoagulant and neuroprotective activities alongside with the water solubility was achieved by introducing glucose. These findings suggest that the introduction of the glucose moiety to scutellarein wattants further development of this kind of compounds as neuroprotective agents.
Li, Nian-Guang,Shen, Min-Zhe,Wang, Zhen-Jiang,Tang, Yu-Ping,Shi, Zhi-Hao,Fu, Yi-Fan,Shi, Qian-Ping,Tang, Hao,Duan, Jian-Ao
p. 102 - 106
(2013/02/23)

Efficient synthesis of 6-o-methyl-scutellarein from scutellarin via selective methylation
Scutellarin (1) possesses distinguished efficacy in the clinical therapy of cerebral infarction, coronary heart disease, and angina pectoris. Scutellarin (1) is readily converted in vivo, therefore, synthetic methods for the construction of its metabolite
Shen, Min-Zhe,Shi, Zhi-Hao,Li, Nian-Guang,Tang, Hao,TangShi, Qian-Ping,Tang, Yu-Ping,Yang, Jian-Ping,Duan, Jin-Ao
p. 733 - 737
(2014/03/21)

Mannich bases of scutellarein as thrombin-inhibitors: Design, synthesis, biological activity and solubility
Two series of 8-aminomethylated derivatives were prepared by Mannich reaction of scutellarein (2) with appropriate aliphatic amines, alicyclic amines and formaldehyde. All the compounds were tested for their thrombin inhibition activity through the analyzation of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen (FIB). The antioxidant activities of these target products were assessed by 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH) assay using 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) assay method and the solubility were assessed by ultraviolet (UV). The results showed that morpholinyl aminomethylene substituent derivative (3d) demonstrated stronger anticoagulant activity, better water solubility and good antioxidant activity compared with scutellarein (2), which warrants further development as a agent for ischemic cerebrovascular disease treatment.
Li, Nian-Guang,Song, Shu-Lin,Shen, Min-Zhe,Tang, Yu-Ping,Shi, Zhi-Hao,Tang, Hao,Shi, Qian-Ping,Fu, Yi-Fan,Duan, Jian-Ao
p. 6919 - 6923
(2013/01/15)

Efficient synthesis of scutellarein
Scutellarein is a component of Scutellaria, recently known as a potent cytotoxic agent on human leukaemia cells. The aim of this study was the synthesis of scutellarein and its methylated derivative. The new features are the innovating method to afford flavones from flavanones and the A-ring regioselective bromination step that lead to the target molecule by a facile and high-yielding pathway.
Righi, Giuliana,Silvestri, Ilaria Proietti,Barontini, Maurizio,Crisante, Fernanda,Di Manno, Andrea,Pelagalli, Romina,Bovicelli, Paolo
experimental part
p. 1278 - 1284
(2012/09/25)

Regioselective hydroxylation of diverse flavonoids by an aromatic peroxygenase
Aromatic peroxygenases are extracellular fungal biocatalysts that selectively oxidize a variety of organic compounds. We found that the peroxygenase of the fungus Agrocybe aegerita (AaeAPO) catalyzes the H 2O2-dependent hydroxylation of diverse flavonoids. The reactions proceeded rapidly and regioselectively yielding preferentially monohydroxylated products, e.g., from flavanone, apigenin, luteolin, flavone as well as daidzein, quercetin, kaempferol, and genistein. In addition to hydroxylation, O-demethylation of fully methoxylated tangeretin was catalyzed by AaeAPO. The enzyme was merely lacking activity on the quercetin glycoside rutin, maybe due to sterical hindrance by the bulky sugar substituents. Mechanistic studies indicated the presence of epoxide intermediates during hydroxylation and incorporation of H2O2-derived oxygen into the reaction products. Our results raise the possibility that fungal peroxygenases may be useful for versatile, cost-effective, and scalable syntheses of flavonoid metabolites.
Barková, Kate?ina,Kinne, Matthias,Ullrich, René,Hennig, Lothar,Fuchs, Annett,Hofrichter, Martin
experimental part
p. 4874 - 4878
(2011/08/03)

New glycosidic constituents of abutilon Pakistanicum
Pakisides A and B (1 and 2, resp.), new catalpol-type iridoid glycosides, and a new glycoside, 3, of scutellarein have been isolated from the AcOEt-soluble fraction of the whole plant of Abutilon pakistanicum, along with buddlejoside and lapachol. The structures of new compounds were elucidated by spectroscopic techniques including 1H-and 13C-NMR (DEPT), and 2D-NMR experiments. Copyright 2010 Verlag Helvetica Chimica Acta AG, Zuerich, Switzerland.
Ali, Bakhat,Fatima, Itrat,Malik, Abdul,Ahmed, Zaheer
experimental part
p. 2245 - 2250
(2011/01/12)

Flavonoids from Scutellaria phyllostachya roots
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Siddikov,Yuldashev,Abdullaev
p. 324 - 325
(2008/04/05)

Importance of the B ring and its substitution on the α-glucosidase inhibitory activity of baicalein, 5,6,7-trihydroxyflavone
Hydroxychroniones and B-ring-substituted 5,6,7-trihydroxyflavones were prepared to evaluate the contribution of the B ring of baicalein (5,6,7-trihydroxyflavone, 1) to its potent α-glucosidase inhibitory activity. Hydroxychromones, which lack 6-hydroxyl substitution, did not show any inhibitory activity, while 5,6,7-trihydroxy-2-methylchromone (5) showed high activity. Among the tested B-ring-substituted 5,6,7-trihydroxyflavones, the 4′-hydroxy-, 3′,4′-dihydroxy-, and 3′,4′,5′- trihydroxy-substituted derivatives were found to give more activity than that of 1. The methoxy-substituted derivatives, however, showed less activity than 1. The results suggest that the B ring of 1 was not essential, although advantageous to the activity; hydroxyl substitution on the B ring of 5,6,7-trihydroxyflavones was favorable to the activity, whereas methoxyl substitution was unfavorable; at least 4′-hydrosyl substitution of 5,6,7-trihydroxyflavones was required for enhanced activity, in which the number of hydroxyl groups did not take part.
Gao, Hong,Kawabata, Jun
p. 1858 - 1864
(2007/10/03)

Metabolites of orally administered Perilla frutescens extract in rats and humans
As a part of our search for bioactive substances from the leaves of Perilla frutescens BRITTON var. acuta KUDO, (Perillae Herba, Labiatae), the aqueous extract was orally administered to rats and humans, and metabolites in the urine, plasma, and/or bile were analyzed by a high-performance liquid chromatograph (HPLC) equipped with a photodiode array detector. When the extract was administered to rats, 10 metabolites, trans-caffeic acid-4-O- sulfate (1), trans-p-coumaric acid-4-O-sulfate (2), trans-ferulic acid-4-O- sulfate (3), trans-m-coumaric acid-3-O-sulfate (4), trans-caffeic acid (5), m-hydroxyphenylpropionic acid (6), trans-p-coumaric acid (7), trans-m- coumaric acid (8), luteolin (9), and apigenin (10) were detected in the urine, whereas four metabolites, scutellarein-6, 7-di-O-β-glucuronide (11), apigenin-4'-O-sulfate-7-O-β-glucuronide (12), apigenin-7-O-β-glucuronide (13), and diosmetin-7-Oβ-glucuronide (14) were found in the bile. Compounds 1-8 and 11-14 were also found in the plasma. When the extract was given to humans, however, two metabolites, 1-O-(2,4,5-trimethoxycinnamoyl)-β- glucuronic acid (15) and apigenin-4'-O-β-glucuronide (16), were found in the urine and plasma. Thus, a species difference in the metabolism of the extract constituents was observed between rats and humans. Structures 1-16 were identified based on their chemical and spectral data.
Nakazawa, Takahiro,Ohsawa, Keisuke
p. 122 - 127
(2007/10/03)

Studies on the Constituents of Scutellaria Species. XI. On the Flavonoid Constituents of the Aerial Parts of Scutellaria indica L.
From the aerial parts of Scutellaria indica L., five new chalcones (I-V) were isolated, together with (2S)-5,6,7,2',3',4',5'-heptamethoxyflavanone, scutellarein 7-O-β-D-glucopyranoside, chrysin, apigenin, luteolin, scutellarein, isoscutellarein, chrysin 7-O-glucuronide, apigenin 7-O-glucuronide, scutellarin and isoscutellarein 8-O-glucuronide.The structures of I-V were shown to be 2'-hydroxy-2,3,4,5,4',5',6'-heptamethoxychalcone, 2,3,4,5,2',4',5',6'-octamethoxychalcone, 2'-hydroxy-2,3,4,5,6'-pentamethoxy-4',5'-methylenedioxychalcone, 2,3,4,5,2',6'-hexamethoxy-4',5'-methylenedioxychalcone, 2,2'-dihydroxy-3,4,5,6'-tetramethoxy-4',5'-methylenedioxychalcone, respectively, on the basis of the chemical and spectral data.Compound I has already been synthesized.Keywords Scutellaria indica; Labiatae; flavonoid; flavone; flavanone; chalcone; structure elucidation
Miyaichi, Yukinori,Kizu, Haruhisa,Tomimori, Tsuyoshi,Lin, Chun-Ching
p. 794 - 797
(2007/10/02)

Scutellarein-7-O-β-D-Glucopyranosyl(1->4)-O-α-L-rhamnopyranoside from the Stems of Thymus serpyllum Linn.
Phytochemical examination of the stems of Thymus serpyllum resulted in the isolation and identification of a glycoside, scutellarein-7-O-β-glucopyranosyl(1->4)-O-α-L-rhamnopyranoside.
Washingtion, J. S.,Saxena, V. K.
p. 226 - 227
(2007/10/02)

TLC, UV AND ACIDIC TREATMENT IN THE DIFFERENTIATION OF 5,6- AND 5,8-DIHYDROXYFLAVONES, 3-METHOXYFLAVONES AND FLAVONOLS
UV and TLC techniques constitute easy procedures to distinguish between 5,6-dihydroxy-7,8-dimethoxy- and 5,8-dihydroxy-6,7-dimethoxyflavonoids, that are difficult to characterize by NMR and classical UV techniques.The acidic treatment of the original products to obtain Wessely-Moser isomers, useful for comparison purposes, yielded novel demethylated products.UV and MS data of 5,8,4' -trihydroxy-6,7,3'-trimethoxyflavone, 5,6,8,3',4'-pentahydroxy-7-methoxyflavone and 5,6,8,4'-tetrahydroxy-7,3'-dimethoxyflavone are presented for the first time.
Barberan, F.A.T.,Ferreres, F.,Tomas, F.
p. 5733 - 5740
(2007/10/02)

Synthetic Studies of the Flavone Derivatives. VIII. Synthesis of Kanzakiflavones and Their Isomers
Kanzakiflavone-1 and -2, isolates from Iris Unguicularis, and their position isomers were synthesized to confirm the structures of the isolates.The differences among these flavones are discussed on the basis of spectral data.Keywords: kanzakiflavone-1; kanzakiflavone-2; 4',5-dihydroxy-7,8-methylenedioxyflavone; 6,7-methylenedioxy-4',5,8-trimethoxyflavone; 7,8-methylenedioxy-4',5,6-trimethoxyflavone; 3'-acetyl-4',5-dihydroxy-6,7-methylenedioxyflavone
Iinuma, Munekazu,Tanaka, Toshiyuki,Matsuura, Shin
p. 1006 - 1010
(2007/10/02)

FLAVONE GLYCOSIDES OF SALVIA TRILOBA
From Salvia triloba, 13 flavonids were isolated and identified.The 7-glucosides and 7-glucoronides of apigenin, luteolin, 6-methoxyapigenin and 6-methoxyluteolin and chrysoeriol 7-glucuronide were identified.Also present were 6,8-di-C-glucosylapigenin, luteolin 7-diglucoside, luteolin 7-glucuronide-3'-glucoside and 6-hydroxy-luteolin 6,3'-dimethyl ether.Key Word Index-Salvia triloba; Labiatae; 6-methoxyflavones; flavone glucosides; chemosystematics.
Abdalla, Mohamed F.,Saleh, Nabiel A. M.,Gabr, Said,Abu-Eyta, Ahmed M.,El-Said, Hani
p. 2057 - 2060
(2007/10/02)

PHYTOCHEMICAL STUDIES ON FLAVONOIDS AND OTHER COMPOUNDS OF JUNIPER FRUITS (JUNIPERUS COMMUNIS L.)
From methanolic extract of juniper fruits (Juniperus communis L.) 7-O-glycosides of: hypolaetin, scutellarein, 7-hydroxy-4',5,6-trimethoxy-flavone, apigenin, as well as 3-O-arabinosyl-glucoside of quercetin were isolated.The presence of rutin, isoquercitrin, 6-O-xylosides of scutellarein and 6-OH luteolin, biflavonoids such as amentoflavone, cupressoflavone were stated too, as described earlier for the compounds isolated from leaves of juniper.The petrol and chloroform extracts from drug were initially analyzed, too.
Lamer-Zarawska, Eliza
p. 213 - 219
(2007/10/02)