- Total synthesis of scutellarin and apigenin 7-O-β-d-glucuronide
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A general protocol for direct glucuronic linkages formation featuring Au(I)-catalyzed appropriately protected glucuronyl o-alkynylbenzoate-involved glycosylation reaction, as well as a concise approach for easy access of scutellarein prominent for the mild and efficient hydroxyl group installation via borylation-oxidation sequence from flavanone derivative, has been established, based on which a novel route for scutellarin derivatives preparation has been devised. The developed strategies, among which the stepwise deprotection process was also included, guarantee the high whole synthetic efficiency, and definitely will find broad application in diversity-oriented synthesis of bioactive flavonoid glycosides.
- Liu, Xin,Wen, Guo-En,Liu, Jian-Chao,Liao, Jin-Xi,Sun, Jian-Song
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supporting information
p. 69 - 73
(2019/03/17)
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- A 5, 4' - dihydroxy flavone - 7 - O - D - glucuronic acid preparation method
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The invention relates to the drug synthesis technical field, and in particular, relates to a preparation method of 5,4'-dihydroxy flavone-7-O-D-glucuronic acid. The method comprises the following steps: taking a compound having a structure represented by the formula II, and under an alkaline condition, acylating to obtain a compound having a structure represented by the formula III; taking the compound having the structure represented by the formula III and alpha-bromo triacetoxy methyl glucuronate, and carrying out a glycosylation reaction, to obtain a compound having a structure represented by the formula IV; taking the compound having the structure represented by the formula IV, and hydrolyzing under an acidic condition, to obtain a compound having a structure represented by the formula V; and taking the compound having the structure represented by the formula V, hydrolyzing under an alkaline condition, and thus obtaining the product. The method provided by the invention has the advantages of cheap and easily obtained starting raw materials, less reaction steps, and simple and easily operated process, and is suitable for large-scale industrialized production; and through testing, the purity of the obtained product can reach more than 98%, and the total yield reaches up to 56%.
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- Identification of flavone glucuronide isomers by metal complexation and tandem mass spectrometry: Regioselectivity of uridine 5′-diphosphate- glucuronosyltransferase isozymes in the biotransformation of flavones
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Flavone glucuronide isomers of five flavones (chrysin, apigenin, luteolin, baicalein, and scutellarein) were differentiated by collision-induced dissociation of [Co(II) (flavone-H) (4,7-diphenyl-1,10-phenanthroline) 2]+ complexes. The complexes were generated via postcolumn addition of a metal-ligand solution after separation of the glucuronide products generated upon incubation of each flavone with an array of uridine 5′-diphosphate (UDP)-glucuronosyltransferase (UGT) isozymes. Elucidation of the glucuronide isomers allowed a systematic investigation of the regioselectivity of 12 human UGT isozymes, including 8 UGT1A and 4 UGT2B isozymes. Glucuronidation of the 7-OH position was the preferred site for all the flavones except for luteolin, which possessed adjacent hydroxyl groups on the B ring. For all flavones and UGT isozymes, glucuronidation of the 5-OH position was never observed. As confirmed by the metal complexation/MS/MS strategy, glucuronidation of the 6-OH position only occurred for baicalein and scutellarein when incubated with three of the UGT isozymes.
- Robotham, Scott A.,Brodbelt, Jennifer S.
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p. 1457 - 1463
(2013/04/23)
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- Accurate prediction of glucuronidation of structurally diverse phenolics by human UGT1A9 using combined experimental and in silico approaches
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Purpose: Catalytic selectivity of human UGT1A9, an important membrane-bound enzyme catalyzing glucuronidation of xenobiotics, was determined experimentally using 145 phenolics and analyzed by 3D-QSAR methods. Methods: Catalytic efficiency of UGT1A9 was determined by kinetic profiling. Quantitative structure activity relationships were analyzed using CoMFA and CoMSIA techniques. Molecular alignment of substrate structures was made by superimposing the glucuronidation site and its adjacent aromatic ring to achieve maximal steric overlap. For a substrate with multiple active glucuronidation sites, each site was considered a separate substrate. Results: 3D-QSAR analyses produced statistically reliable models with good predictive power (CoMFA: q 2=0.548, r2=0.949, r pred 2 =0.775; CoMSIA: q2=0.579, r2=0.876, rpred2 =0.700). Contour coefficient maps were applied to elucidate structural features among substrates that are responsible for selectivity differences. Contour coefficient maps were overlaid in the catalytic pocket of a homology model of UGT1A9, enabling identification of the UGT1A9 catalytic pocket with a high degree of confidence. Conclusion: CoMFA/CoMSIA models can predict substrate selectivity and in vitro clearance of UGT1A9. Our findings also provide a possible molecular basis for understanding UGT1A9 functions and substrate selectivity.
- Wu, Baojian,Wang, Xiaoqiang,Zhang, Shuxing,Hu, Ming
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experimental part
p. 1544 - 1561
(2012/07/27)
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- Co-pigmentation and flavonoid glycosyltransferases in blue Veronica persica flowers
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Glycosylation is one of the key modification steps for plants to produce a broad spectrum of flavonoids with various structures and colors. A survey of flavonoids in the blue flowers of Veronica persica Poiret (Lamiales, Scrophulariaceae), which is native of Eurasia and now widespread worldwide, led to the identification of highly glycosylated flavonoids, namely delphinidin 3-O-(2-O-(6-O-p-coumaroyl-glucosyl)-6-O-p-coumaroyl-glucoside)-5-O-glucoside (1) and apigenin 7-O-(2-O-glucuronosyl)-glucuronide (2), as two of its main flavonoids. Interestingly, the latter flavone glucuronide (2) caused a bathochromic shift on the anthocyanin (1) toward a blue hue in a dose-dependent manner, showing an intermolecular co-pigment effect. In order to understand the molecular basis for the biosynthesis of this glucuronide, we isolated a cDNA encoding a UDP-dependent glycosyltransferase (UGT88D8), based on the structural similarity to flavonoid 7-O-glucuronosyltransferases (F7GAT) from Lamiales plants. Enzyme assays showed that the recombinant UGT88D8 protein catalyzes the 7-O-glucuronosylation of apigenin and its related flavonoids with preference to UDP-glucuronic acid as a sugar donor. Furthermore, we identified and functionally characterized a cDNA encoding another UGT, UGT94F1, as the anthocyanin 3-O-glucoside-2″-O-glucosyltransferase (A3Glc2″GlcT), according to the structural similarity to sugar-sugar glycosyltransferases classified to the cluster IV of flavonoid UGTs. Preferential expression of UGT88D8 and UGT94F1 genes in the petals supports the idea that these UGTs play an important role in the biosynthesis of key flavonoids responsible for the development of the blue color of V. persica flowers.
- Ono, Eiichiro,Ruike, Miho,Iwashita, Takashi,Nomoto, Kyosuke,Fukui, Yuko
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experimental part
p. 726 - 735
(2010/07/02)
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