6160-80-1

Basic information

• Product Name: 4-Methylumbelliferyl-beta-D-glucuronide
• Synonyms: 4-METHYL-2-OXO-2H-1-BENZOPYRAN-7-YL, BETA-D-GLUCO-PYRANOSIDURONIC ACID;4-METHYLUMBELLIFERYL B-D-GLUCURONIDE;4-METHYLUMBELLIFERYL-BETA-D-GLUCURONIC ACID;4-METHYLUMBELLIFERYL-BETA-D-GLUCURONIDE;MUG;MUGLCU;.beta.-D-Glucopyranosiduronicacid,4-methyl-2-oxo-2H-1-benzopyran-7-yl;4-methylumbelliferylglucuronide
• CAS NO: 6160-80-1
• Molecular Formula: C₁₆H₁₆O₉
• Molecular Weight: 352.29284
• EINECS: 228-186-0
• Product Categories: Substrates;Fluorescent Labels & Indicators;Glucuronides;substrate
• Mol File: 6160-80-1.mol
• Article Data: 11

Chemical Properties

• Melting Point: 102 °C
• Boiling Point: 683.106 °C at 760 mmHg
• Flash Point: 254.961 °C
• Appearance: /
• Density: 1.632 g/cm₃
• Vapor Pressure: 1.35E-19mmHg at 25°C
• Storage Temp.: −20°C
• Solubility: Methanol (Slightly), Water (Slightly)
• PKA: 2.76±0.70(Predicted)
• Water Solubility: slightly soluble
• Sensitive: Moisture Sensitive
• CAS DataBase Reference: 4-Methylumbelliferyl-beta-D-glucuronide(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Methylumbelliferyl-beta-D-glucuronide(6160-80-1)
• EPA Substance Registry System: 4-Methylumbelliferyl-beta-D-glucuronide(6160-80-1)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 22-40
• Safety Statements: 24/25-36/37
• WGK Germany: 3
• TSCA: Yes
• Hazardous Substances Data: 6160-80-1(Hazardous Substances Data)

Usage

Description

4-Methylumbelliferyl-beta-D-glucuronide is a fluorescent substrate of β-glucuronidase. Once cleaved, 4-Methylumbelliferyl-beta-D-glucuronide yields blue fluorescence seen under UV light which is pH-dependent with excitation maxima of 320 and 360 nm at low (1.97-6.72) and high (7.12-10.3) pH, respectively. It is ideal for working with Escherichia coli and plant molecular studies.

Chemical Properties

Crystalline

Uses

Different sources of media describe the Uses of 6160-80-1 differently. You can refer to the following data:
1. 4-Methylumbelliferyl-beta-D-glucuronide is a substrate for glucuronidase. Also used as a test for coliform bacteria in water. Fluorescence: max. Abs. 316nm; max. Em. 375nm; e x 10-3: 12
2. Substrate for ?-D-glucuronidase assay. MUG is widely used as component of selective microbial culture media.
3. 4-Methylumbelliferyl β-D-glucuronide dihydrate is a useful building block and a fluorophore.

Definition

ChEBI: A beta-D-glucosiduronic acid having a 4-methylumbelliferyl substituent at the anomeric position.

InChI:InChI=1/C16H16O9/c1-6-4-10(17)24-9-5-7(2-3-8(6)9)23-16-13(20)11(18)12(19)14(25-16)15(21)22/h2-5,11-14,16,18-20H,1H3,(H,21,22)/p-1/t11-,12+,13+,14-,16+/m0/s1

Synthetic route

methyl (4′-methylumbelliferyl 2,3,4-tri-O-acetyl-β-D-glucopyranosid)urinate (101014-65-7) → 4-methylumbelliferyl-β-D-glucuronide (6160-80-1)

Conditions	Yield
With water; potassium carbonate In methanol; dichloromethane at 0 - 5℃; for 12h;	89%
With barium hydroxide monohydrate In methanol; water for 4h; Inert atmosphere; Cooling with ice;	47%
With barium hydroxide monohydrate In methanol; water at 0℃; for 4h; Inert atmosphere;	47%
Multi-step reaction with 2 steps 1: NaOMe; MeOH / 1 h / 20 °C 2: 0.068 mmol / LiOH / tetrahydrofuran; H2O / 1 h / 20 °C View Scheme

4-methylumbelliferyl-2,3,4-tri-O-acetyl-β-D-glucopyranosiduronic acid (937018-37-6) → 4-methylumbelliferyl-β-D-glucuronide (6160-80-1)

Conditions	Yield
With barium methoxide In methanol at 0 - 5℃; for 24h;	85%

7-hydroxy-4-methyl-chromen-2-one (90-33-5, 79566-13-5) + UDP-glucuronic acid (2616-64-0) → 4-methylumbelliferyl-β-D-glucuronide (6160-80-1)

Conditions	Yield
With UGT88D4 In aq. buffer at 30℃; for 12h; Reagent/catalyst; Solvent; Enzymatic reaction;	75%
With rat liver microsome solution; magnesium chloride In various solvent(s) at 37℃; for 0.166667h; pH=7.4;

4-methylumbelliferyl β-D-glucopyranoside (18997-57-4) → 4-methylumbelliferyl-β-D-glucuronide (6160-80-1)

Conditions	Yield
With oxygen; sodium hydrogencarbonate; platinum at 90℃;
Multi-step reaction with 5 steps 1: pyridine / 5 h / 90 - 100 °C 2: 7.60 g / pyridine / 24 h / 20 °C 3: 92 percent / iodine; methanol / benzene / 24 h / 65 °C 4: 68 percent / aqueous sodium hypochlorite; TBAB; NaBr / 2,2,6,6-tetramethyl-1-piperidinyloxy; tetrabutylammonium bromide / aq. NaHCO3; CH2Cl2 / 3 h / 0 °C 5: 85 percent / barium methoxide / methanol / 24 h / 0 - 5 °C View Scheme

methyl 4-methylcoumarin-7-yl-β-D-glucopyranuronate (116523-82-1) → 4-methylumbelliferyl-β-D-glucuronide (6160-80-1)

Conditions	Yield
With lithium hydroxide In tetrahydrofuran; water at 20℃; for 1h;	0.068 mmol

4-methylumbelliferyl-2,3,4-tri-O-acetyl-β-glucopyranoside (937018-36-5) → 4-methylumbelliferyl-β-D-glucuronide (6160-80-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 68 percent / aqueous sodium hypochlorite; TBAB; NaBr / 2,2,6,6-tetramethyl-1-piperidinyloxy; tetrabutylammonium bromide / aq. NaHCO3; CH2Cl2 / 3 h / 0 °C 2: 85 percent / barium methoxide / methanol / 24 h / 0 - 5 °C View Scheme

4-methyl-7-(3,4,5-trihydroxy-6-trityloxymethyl-tetrahydro-pyran-2-yloxy)-chromen-2-one → 4-methylumbelliferyl-β-D-glucuronide (6160-80-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: 7.60 g / pyridine / 24 h / 20 °C 2: 92 percent / iodine; methanol / benzene / 24 h / 65 °C 3: 68 percent / aqueous sodium hypochlorite; TBAB; NaBr / 2,2,6,6-tetramethyl-1-piperidinyloxy; tetrabutylammonium bromide / aq. NaHCO3; CH2Cl2 / 3 h / 0 °C 4: 85 percent / barium methoxide / methanol / 24 h / 0 - 5 °C View Scheme

4-methylumbelliferyl-2,3,4-tri-O-acetyl-6-O-trityl-β-D-glucopyranoside (937018-35-4) → 4-methylumbelliferyl-β-D-glucuronide (6160-80-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 92 percent / iodine; methanol / benzene / 24 h / 65 °C 2: 68 percent / aqueous sodium hypochlorite; TBAB; NaBr / 2,2,6,6-tetramethyl-1-piperidinyloxy; tetrabutylammonium bromide / aq. NaHCO3; CH2Cl2 / 3 h / 0 °C 3: 85 percent / barium methoxide / methanol / 24 h / 0 - 5 °C View Scheme

sodium 4-methylumbelliferonate (5980-33-6) → 4-methylumbelliferyl-β-D-glucuronide (6160-80-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 45 percent / benzyltriethylammonium chloride; aq. NaOH / CHCl3 / 5 h / Heating 2: NaOMe; MeOH / 1 h / 20 °C 3: 0.068 mmol / LiOH / tetrahydrofuran; H2O / 1 h / 20 °C View Scheme

1-bromo-2,3,4-tri-O-acetyl-α-D-glucuronic acid methyl ester (21085-72-3) → 4-methylumbelliferyl-β-D-glucuronide (6160-80-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 45 percent / benzyltriethylammonium chloride; aq. NaOH / CHCl3 / 5 h / Heating 2: NaOMe; MeOH / 1 h / 20 °C 3: 0.068 mmol / LiOH / tetrahydrofuran; H2O / 1 h / 20 °C View Scheme

7-hydroxy-4-methyl-chromen-2-one (90-33-5, 79566-13-5) + uridine-5'-diphospho-α-D-glucuronic acid trisodium salt (63700-19-6) → 4-methylumbelliferyl-β-D-glucuronide (6160-80-1)

Conditions	Yield
With magnesium chloride In phosphate buffer at 37℃; for 1.25h; pH=7.4; Enzyme kinetics; Further Variations:; Solvents;
With recombinant human UDP-glucuronosyltransferase isoform 1A7; magnesium chloride In dimethyl sulfoxide pH=7.4; Kinetics; Reagent/catalyst; Enzymatic reaction;

7-hydroxy-4-methyl-chromen-2-one (90-33-5, 79566-13-5) + uridine diphosphate glucuronic acidammonium salt → 4-methylumbelliferyl-β-D-glucuronide (6160-80-1)

Conditions	Yield
With magnesium(II) chloride hexahydrate; recombinant human uridine 5′-diphosphate-glucuronosyltransferase 1A9; bovine serum albumin In aq. phosphate buffer at 37℃; for 1h; pH=7.4; Kinetics; Time; Concentration; Reagent/catalyst; Darkness; Enzymatic reaction;

7-hydroxy-4-methyl-chromen-2-one (90-33-5, 79566-13-5) + α-D-glucuronyl fluoride (777038-38-7) → 4-methylumbelliferyl-β-D-glucuronide (6160-80-1)

Conditions	Yield
With Escherichia coli β-glucuronidase E504G mutant In aq. phosphate buffer; tert-butyl alcohol at 37℃; for 48h; pH=7.5; Enzymatic reaction;

7-hydroxy-4-methyl-chromen-2-one (90-33-5, 79566-13-5) + (2S,3S,4S,5R,6S)-3,4,5,6-Tetraacetoxy-tetrahydro-pyran-2-carboxylic acid methyl ester (7355-18-2) → 4-methylumbelliferyl-β-D-glucuronide (6160-80-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: boron trifluoride diethyl etherate; dmap / 1,2-dichloro-ethane / 5 h / 60 °C / Inert atmosphere 2: barium hydroxide monohydrate / water; methanol / 4 h / Inert atmosphere; Cooling with ice View Scheme
Multi-step reaction with 2 steps 1: boron trifluoride diethyl etherate; dmap / 1,2-dichloro-ethane / 5 h / 60 °C / Inert atmosphere 2: barium hydroxide monohydrate / water; methanol / 4 h / Inert atmosphere; Cooling with ice View Scheme
Multi-step reaction with 2 steps 1: triethylamine; boron trifluoride diethyl etherate / dichloromethane / 72 h / 20 °C / Inert atmosphere 2: barium hydroxide monohydrate / water; methanol / 4 h / 0 °C / Inert atmosphere View Scheme

diazomethane (186581-53-3, 908094-01-9) + acetic anhydride (108-24-7) + 4-methylumbelliferyl-β-D-glucuronide (6160-80-1) → methyl (4′-methylumbelliferyl 2,3,4-tri-O-acetyl-β-D-glucopyranosid)urinate (101014-65-7)

Conditions	Yield
With pyridine; diethyl ether Reaktion ueber zwei Stufen;

4-methylumbelliferyl-β-D-glucuronide (6160-80-1) → 7-hydroxy-4-methyl-chromen-2-one (90-33-5, 79566-13-5)

Conditions	Yield
With ethylenediaminetetraacetic acid; sodium acetate; Triton X-100; β-glucuronidase in human liver homogenate at 37℃; for 0.5h; pH=5; Enzyme kinetics; Further Variations:; Catalysts;

UDP disodium + 4-methylumbelliferyl-β-D-glucuronide (6160-80-1) → 7-hydroxy-4-methyl-chromen-2-one (90-33-5, 79566-13-5)

Conditions	Yield
With magnesium(II) chloride hexahydrate; recombinant human uridine 5′-diphosphate-glucuronosyltransferase 1A9; bovine serum albumin In aq. phosphate buffer at 37℃; for 1h; pH=7.4; Kinetics; Time; Reagent/catalyst; Darkness; Enzymatic reaction;

methanol (67-56-1) + 4-methylumbelliferyl-β-D-glucuronide (6160-80-1) → methyl 4-methylcoumarin-7-yl-β-D-glucopyranuronate (116523-82-1)

Conditions	Yield
With sulfuric acid at 65℃; for 1h;

4-methylumbelliferyl-β-D-glucuronide (6160-80-1) → D-glucuronic acid (489-91-8, 528-16-5, 552-12-5, 577-46-8, 643-33-4, 2240-07-5, 6294-16-2, 10133-02-5, 18402-78-3, 18968-14-4, 21179-08-8, 23018-83-9, 33599-45-0, 33599-46-1, 46171-67-9, 46171-69-1, 46172-26-3, 70021-34-0, 71031-08-8, 104195-06-4, 106499-29-0, 124817-72-7) + 6-hydroxy-4-methyl-chromen-2-one (2373-31-1)

Conditions	Yield
With β-glucuronidase In aq. phosphate buffer pH=7.4; Concentration; Enzymatic reaction;

Upstream product

• 18997-57-4 4-methylumbelliferyl β-D-glucopyranoside 
• 90-33-5 7-hydroxy-4-methyl-chromen-2-one 
• 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 
• 63700-19-6 uridine-5'-diphospho-α-D-glucuronic acid trisodium salt 
• 21085-72-3 1-bromo-2,3,4-tri-O-acetyl-α-D-glucuronic acid methyl ester 
• 101014-65-7 methyl (4′-methylumbelliferyl 2,3,4-tri-O-acetyl-β-D-glucopyranosid)urinate 
• 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 
• 2616-64-0 UDP-glucuronic acid 
• 5980-33-6 sodium 4-methylumbelliferonate 

Downstream Products

• 90-33-5 7-hydroxy-4-methyl-chromen-2-one 
• 489-91-8 D-glucuronic acid 
• 2373-31-1 6-hydroxy-4-methyl-chromen-2-one 
• 116523-82-1 methyl 4-methylcoumarin-7-yl-β-D-glucopyranuronate 

Relevant articles and documents

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A new synthetic route to 4-methylumbelliferyl-β-D-glucopyranosiduronic acid (MUG)

A synthetic route to prepare 4-methylumbelliferyl-β-D- glucopyranosiduronic acid (MUG) from 4-methylumbelliferyl-β-D- glucopyranoside (MUGluc) was developed. The primary hydroxyl group in MUGluc was protected by tritylation followed by acetylation of secondary hydroxyls. The triphenylmethyl group was selectively removed by treatment with iodine-methanol in benzene and the free hydroxyl was transformed into the carboxylic acid by phase-transfer oxidation with sodium hypochlorite and TEMPO as catalyst. Finally, the acetate groups were removed by reaction with barium methoxide in methanol to afford the MUG with an overall yield of 37% from the MUGluc. Georg Thieme Verlag Stuttgart.

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.

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.