84434-84-4

Upstream product

• 90-33-5 7-hydroxy-4-methyl-chromen-2-one 
• 2616-64-0 UDP-glucuronic acid 
• 63700-19-6 uridine-5'-diphospho-α-D-glucuronic acid trisodium salt 
• 66895-31-6 1-(4-methylumbelliferone)-2,3,4,6-tetra-O-acetyl-α-L-idopyranose 
• 2152-77-4 1,2,3,4,6-penta-O-acetyl-α-L-idopyranose 
• 66901-41-5 1-(4-methylumbelliferone)-α-L-idopyranoside 
• 7355-18-2 (2S,3S,4S,5R,6S)-3,4,5,6-Tetraacetoxy-tetrahydro-pyran-2-carboxylic acid methyl ester 
• 777038-38-7 α-D-glucuronyl fluoride 
• 21085-72-3 1-bromo-2,3,4-tri-O-acetyl-α-D-glucuronic acid methyl ester 
• 937018-35-4 4-methylumbelliferyl-2,3,4-tri-O-acetyl-6-O-trityl-β-D-glucopyranoside 
• 937018-36-5 4-methylumbelliferyl-2,3,4-tri-O-acetyl-β-glucopyranoside 
• 937018-37-6 4-methylumbelliferyl-2,3,4-tri-O-acetyl-β-D-glucopyranosiduronic acid 
• 116523-82-1 methyl 4-methylcoumarin-7-yl-β-D-glucopyranuronate 
• 18997-57-4 4-methylumbelliferyl β-D-glucopyranoside 

Downstream Products

• 116523-82-1 methyl 4-methylcoumarin-7-yl-β-D-glucopyranuronate 

Relevant academic research and scientific papers

Interaction of bisphenol A with human UDP-glucuronosyltransferase 1A6 enzyme

The effects of bisphenol A (BPA) on UDP-glucuronosyltransferase 1A6 (UGT1A6) activities in microsomes from human livers and yeast cells expressing human UGT1A6 (humUGT1A6) were investigated. Serotonin (5-HT) and 4-methylumbelliferone (4-MU) were used as the substrates for UGT1A6. BPA dose-dependently inhibited 5-HT and 4-MU glucuronidation activities in both enzyme sources. The IC50 values of BPA for 5-HT and 4-MU glucuronidation activities were 156 and 163 μM for liver microsomes, and 84.6 and 80.3 μM for yeast cell microsomes expressing humUGT1A6, respectively. The inhibitory pattern of BPA for 5-HT and 4-MU glucuronidation activities in human liver microsomes exhibited a mixture of competitive and noncompetitive components, with Ki values of 84.9 and 72.3 μM, respectively. In yeast cell microsomes expressing humUGT1A6, 5-HT glucuronidation activities were noncompetitively inhibited by BPA (Ki value, 65.5 μM), whereas the inhibition of 4-MU glucuronidation activities by BPA exhibited the mixed type (Ki value, 42.5 μM). These results suggest that BPA interacts with human UGT1A6 enzyme, and that the interaction may contribute to the toxicity, such as hormone disruption and reproductive effects, of BPA.

Synthetic method of fluorescent glycosidase substrate for determination of alpha-L-iduronidase

The invention relates to a synthesis method of a fluorescent glycosidase substrate for determination of alpha-L-iduronidase. According to the method, coumarin-beta-D-glucuronide is used as a raw material; the preparation method comprises the following steps: adding N-bromosuccinimide and a chlorinated organic solvent under an illumination condition by using a Wohl-Ziegler free radical reaction, and carrying out reflux stirring; then, spin-drying the organic solvent under reduced pressure; dissolving and extracting by using an organic solvent, collecting an organic phase, spin-drying the solvent, carrying out silica gel column chromatography separation to obtain a brominated compound, carrying out free radical reduction in the organic solvent, spin-drying the solvent, carrying out silica gel column chromatography separation to obtain coumarin-alpha-L-iduronide, and finally removing a protecting group to obtain coumarin-alpha-L-iduronide. The coumarin-alpha-L-iduronide is synthesized bya method of free radical substitution and reduction of coumarin-beta-D-glucuronide for the first time, and the reaction has the characteristics of simplicity and convenience in operation, simple and easily available raw materials, easiness in product separation, high reaction yield and the like.

Synthesis method for Beta-glucuronidase precipitation type fluorometric substrate

The invention discloses a synthesis method for a Beta-glucuronidase precipitation type fluorometric substrate based on 2-(benzothiazole-2'-yl)-4-bromophenol. The synthesis method comprises the following three steps of reaction: (1) glycosylation reaction; (2) aromatic cyclization reaction; (3) protecting group removal reaction. The yield of each step of reaction in the synthesis method can reach the medium level or more and even up to more than 90 percent, the reaction conversion rate of materials with high prices or preparation costs is relatively high, the total yield of the three steps canreach 37 percent, moreover, the reaction condition is mild, and the synthesis method is easy to implement. Furthermore, the step of glycosylation reaction and the step of protecting group removal reaction in the synthesis method can be applied.

Enzymatic Synthesis of Bioactive O-Glucuronides Using Plant Glucuronosyltransferases

Many O-glucuronides exhibiting various pharmacological activities have been found in nature and in drug metabolism. The glucuronidation of bioactive natural products or drugs to generate glucuronides with better activity and druggability is important in drug discovery and research. In this study, by using two uridine diphosphate (UDP)-dependent glucuronosyltransferases (GATs, UGT88D4 and UGT88D7) from plants, we developed two glucuronidation approaches, pure enzyme catalysis in vitro and recombinant whole-cell catalysis in vivo, to efficiently synthesize bioactive O-glucuronides by the glucuronidation of natural products. In total, 14 O-glucuronides with different structures, including flavonoids, anthraquinones, coumarins, and lignans, were obtained, 7 of which were new compounds. Furthermore, one of the biosynthesized O-glucuronides, kaempferol-7-O-β-d-glucuronide (3a), potently inhibited protein tyrosine phosphatase (PTP) 1B with an IC50 value of 8.02 × 10-6 M. Some of the biosynthesized O-glucuronides also exhibited significant antioxidant activities.

Based on 4 - methyl [...] synthesis method of a plurality of glycoside

The invention discloses a method for synthesizing various glucosides on a basis of 4-methylumbelliferone. According to the invention, a glycosyl donor peracetyl saccharide and a glycosyl acceptor 4-methylumbelliferone are subjected to a glycosylation reaction under room temperature or under heating with dichloromethane or 1,2-dichloroethane as a solvent and with the combined effect of Lewis acid boron trifluoride ethyl ether and organic alkali triethylamine or pyridine; and protecting groups are removed, such that various glucosides based on 4-methylumbelliferone can be obtained. The glucosides include 4-methylumbelliferone-beta-D-glucopyranosiduronide, 4-methylumbelliferone-beta-D-glucopyranoside, 4-methylumbelliferone-beta-D-xylopyranoside, 4-methylumbelliferone-beta-D-ribofuranoside, 4-methylumbelliferone-alpha-D-galactopyranoside, and 4-methylumbelliferone-alpha-D-mannopyranoside. The method is simple, and can produce a beta or alpha single-configuration target. A glycosylation reaction yield can reach 17-93%.

Method for the diagnosis of lysosomal storage diseases

The present invention relates to a method for the diagnosis of a lysosomal storage disease (LSD) in a subject which is based on determining the activity of lysosomal enzymes with the help of 4-alkyl umbelliferyl derivatives. The present invention further relates to said 4-alkyl umbelliferyl derivatives for use in the diagnosis of an LSD, and a kit for the diagnosis of an LSD.

Chirality influence of zaltoprofen towards UDP-glucuronosyltransferases (UGTs) inhibition potential

Abstract Zaltoprofen (ZLT) is a nonsteroidal antiinflammation drug, and has been clinically employed to treat rheumatoid arthritis, osteoarthritis, and other chronic inflammatory pain conditions. The present study aims to investigate the chirality influence of zaltoprofen towards the inhibition potential towards UDP-glucuronosyltransferases (UGTs) isoforms. In vitro a recombinant UGT isoforms-catalyzed 4-methylumbelliferone (4-MU) glucuronidation incubation system was employed to investigate the inhibition of (R)-zaltoprofen and (S)-zaltoprofen towards UGT isoforms. The inhibition difference capability was observed for the inhibition of (R)-zaltoprofen and (S)-zaltoprofen towards UGT1A8 and UGT2B7, but not for other tested UGT isoforms. (R)-zaltoprofen exhibited noncompetitive inhibition towards UGT1A8 and competitive inhibition towards UGT2B7. The inhibition kinetic parameters were calculated to be 35.3 μM and 19.2 μM for UGT1A8 and UGT2B7. (R)-zaltoprofen and (S)-zaltoprofen exhibited a different inhibition type towards UGT1A7. Based on the reported maximum plasma concentration of (R)-zaltoprofen in vivo, a high drug-drug interaction between (R)-zaltoprofen and the drugs mainly undergoing UGT1A7, UGT1A8, and UGT2B7-catalyzed glucuronidation was indicated. Chirality 27:359-363, 2015.

An improved helferich method for the α/β-stereoselective synthesis of 4-methylumbelliferyl glycosides for the detection of microorganisms

An improved Helferich method is presented. It involves the glycosylation of 4-methyl-umbelliferone with glycosyl acetates in the presence of boron trifluoride etherate combined with triethylamine, pyridine, or 4-dimethylaminopyridine under mild conditions, followed by deprotection to give fluorogenic 4-methylumbelliferyl glycoside substrates. Due to the use of base, the glycosylation reaction proceeds more easily, is uncommonly α- or β-stereoselective, and affords the corresponding products in moderate to excellent yields (51%-94%) under appropriate conditions.

Characterization of the zebrafish Ugt repertoire reveals a new class of drug-metabolizing UDP glucuronosyltransferases

The zebrafish genome contains a gene superfamily of 40 Ugt genes that can be divided into Ugt1, Ugt2, and Ugt5 families. Because the encoded zebrafish UDP glucuronosyltransferase (UGT) proteins do not display orthologous relationships to any of the mammalian and avian UGT enzymes based on molecular phylogeny, it is difficult to predict their substrate specificity. Here, we mapped their tissue-specific expression patterns. We showed that the zebrafish UGT enzymes can be glycosylated. We determined their substrate specificity and catalytic activity toward diverse aglycone substrates. Specifically, we measured mRNA levels of each of the 40 zebrafish Ugt genes in 11 adult tissues and found that they are expressed in a tissue-specific manner. Moreover, functional analyses with the donor of UDP glucuronic acid (UDPGA) for each of the 40 zebrafish UGT proteins revealed their substrate specificity toward 10 important aglycones. In particular, UGT1A1, UGT1A7, and UGT1B1 displayed good glucuronidation activities toward most phenolic aglycones (4-methylumbelliferone, 4-nitrophenol, 1-naphthol, bisphenol A, and mycophenolic acid) and the two carboxylic acids (bilirubin and diclofenac). Importantly, some members of the UGT5, a novel UGT family identified recently, are capable of glucuronidating multiple aglycones with the donor cofactor of UDPGA. In particular, UGT5A5, UGT5B2, and UGT5E1 glucuronidate phenols and steroids with high specificity toward steroid hormones of estradiol and testosterone and estrogenic alkylphenols 4-tert-octylphenol. These results shed new insights into the mechanisms by which fish species defend themselves against vast numbers of xenobiotics via glucuronidation conjugations and may facilitate the establishment of zebrafish as a model vertebrate in toxicological, developmental, and pathologic studies. Copyright

Validated assay for the evaluation of multiple glucuronidation activities in human liver microsomes via liquid chromatography-tandem mass spectrometry

A sensitive and high-throughput liquid chromatography-tandem mass spectrometry system was developed and validated for the simultaneous determination of major human hepatic UDP-glucuronyltransferase forms in human liver microsomes. The analytes were detected using a triple-quadrupole mass spectrometer equipped with an electrospray ionization source in the negative ion and selected reaction monitoring modes. The method provided satisfactory linear concentration range, accuracy, precision, and stability. The developed method was successfully applied to the enzyme kinetic study of estradiol-3-O-glucuronidation, 4-methylumbelliferone-O-glucuronidation, propofol-O-glucuronidation, and 3-azido-3-deoxythymidine glucuronidation in human liver microsomes.