112828-15-6

Basic information

• Product Name: (R)-Naproxen Acyl-b-D-glucuronide
• Synonyms: (R)-Naproxen Acyl--D-glucuronide;(R)-Naproxen Glucuronide;1-[(aR)-6-Methoxy-a-methyl-2-naphthaleneacetate] -D-Glucopyranuronic Acid;(R)-Naproxen acyl-β-D-glucuronide ,98%;1-[(αR)-6-Methoxy-α-Methyl-2-naphthaleneacetate]
• CAS NO: 112828-15-6
• Molecular Formula: C20H22O9
• Molecular Weight: 406.385
• Product Categories: Chiral Reagents;Glucuronides;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 112828-15-6.mol
• Article Data: 5

Chemical Properties

• Melting Point: 128-130°C
• Appearance: /
• Refractive Index: 1.652
• Storage Temp.: Hygroscopic, -20°C Freezer, Under Inert Atmosphere
• Solubility: Methanol (Slightly)
• Stability: Hygroscopic
• CAS DataBase Reference: (R)-Naproxen Acyl-b-D-glucuronide(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-Naproxen Acyl-b-D-glucuronide(112828-15-6)
• EPA Substance Registry System: (R)-Naproxen Acyl-b-D-glucuronide(112828-15-6)

Safety Data

• Hazardous Substances Data: 112828-15-6(Hazardous Substances Data)

Usage

Description

(R)-Naproxen Acyl-b-D-glucuronide is a metabolite of Naproxen, a nonsteroidal anti-inflammatory drug (NSAID) commonly used for pain relief, inflammation reduction, and fever management. It is a white to off-white solid and is formed through the glucuronidation process in the liver, which is a phase II biotransformation reaction that helps in the elimination of the parent drug from the body.

Uses

Used in Pharmaceutical Industry:
(R)-Naproxen Acyl-b-D-glucuronide is used as a metabolite in the pharmaceutical industry for the development and study of Naproxen as a therapeutic agent. Understanding its properties and behavior can help in optimizing drug dosages, minimizing side effects, and improving patient outcomes.
Used in Drug Metabolism and Pharmacokinetics Research:
(R)-Naproxen Acyl-b-D-glucuronide is used as a research tool in drug metabolism and pharmacokinetics studies. It aids in understanding the metabolic pathways of Naproxen, its elimination from the body, and its potential interactions with other drugs or substances.
Used in Toxicology and Safety Assessment:
(R)-Naproxen Acyl-b-D-glucuronide is used in toxicology and safety assessment to evaluate the potential toxic effects of Naproxen and its metabolites. This information is crucial for determining the safety profile of the drug and establishing appropriate guidelines for its use.
Used in Quality Control and Drug Analysis:
(R)-Naproxen Acyl-b-D-glucuronide is used in quality control and drug analysis to ensure the purity, potency, and consistency of Naproxen-containing pharmaceutical products. Analyzing the presence and quantity of this metabolite can help in monitoring the manufacturing process and maintaining product quality.

InChI:InChI=1/C20H22O9/c1-9(10-3-4-12-8-13(27-2)6-5-11(12)7-10)19(26)29-20-16(23)14(21)15(22)17(28-20)18(24)25/h3-9,14-17,20-23H,1-2H3,(H,24,25)/t9-,14-,15-,16-,17?,20-/m1/s1

Upstream product

• 41945-43-1 (+)-Naproxen glucuronide 
• 912805-98-2 (S)-naproxen 1-β-O-acyl glucuronide methyl ester 
• 159420-94-7 benzyl <1-O-trichloroethanimidoyl>-2,3,4-tri-O-benzyl-D-glucopyranuronate 
• 22204-53-1 (2S)-2-(6-methoxy(2-naphthyl))propanoic acid 
• 946517-36-8 C₂₇H₂₈O₉ 
• 23979-41-1 (R)-2-(6-methoxy-2-naphthyl)propionic acid 
• 2616-64-0 uridine diphosphoglucuronic acid 

Relevant articles and documents

HPLC/1H NMR spectroscopic studies of the reactive alpha-1-O-acyl isomer formed during acyl migration of S-naproxen beta-1-O-acyl glucuronide.

A widely held view in drug metabolism and pharmacokinetic studies is that the initial 1-isomer to 2-isomer step in the intramolecular acyl migration of drug ester glucuronides is irreversible, and that alpha-1-O-acyl isomers do not occur under physiological conditions. We investigated this hypothesis using high-performance liquid chromatography directly coupled to proton nuclear magnetic resonance spectroscopy (HPLC/1H NMR) and mass spectrometry (LC/MS) to probe the migration reactions of S-naproxen beta-1-O-acyl glucuronide, in phosphate buffer at pH 7.4, 37 degrees C. We report the first direct observation of the alpha-1-O-acyl isomer of a drug ester glucuronide (S-naproxen) formed in a biosystem via the facile acyl migration of the corresponding pure beta-1-O-acyl glucuronide. The unequivocal identification of the reactive product was achieved using stopped-flow one-dimensional HPLC/1H NMR and two-dimensional 1H-1H total correlation spectroscopy (1H-1H TOCSY). Parallel LC/ion-trap mass spectrometry yielded the confirmatory glucuronide masses. Moreover, dynamic stopped-flow HPLC/1H NMR experiments revealed transacylation of the isolated alpha-1-O-acyl isomer to a mixture of alpha/beta-2-O-acyl isomers; the reverse reaction from the isolated alpha/beta-2-O-acyl isomers to the alpha-1-O-acyl isomer was also clearly demonstrated. This application of dynamic stopped-flow HPLC/1H NMR allows key kinetic data to be obtained on a reactive metabolite that would otherwise be difficult to follow by conventional HPLC and NMR methods where sample preparation and off-line separations are necessary. These data challenge the widely held view that the alpha-1-O-acyl isomers of drug ester glucuronides do not occur under physiological conditions. Furthermore, the similar formation of alpha-1-O-acyl isomers from zomepirac and diflunisal beta-1-O-acyl glucuronides has recently been confirmed (Corcoran et al., unpublished results). Such reactions are also likely to be widespread for other drugs that form ester glucuronides in biological systems. Ultimately, the presence of significant quantities of the kinetically labile alpha-1-O-acyl glucuronide isomer may also have toxicological implications in terms of reactivity toward cellular proteins.

Efficient synthesis of 1β-O-acyl glucuronides via selective acylation of allyl or benzyl d-glucuronate

Acyl glucuronides are key metabolites for many carboxylic acid-containing drugs, notably those of the non-steroidal anti-inflammatory class. In the processes of drug safety assessment and new drug development, it is essential that acyl glucuronides, if formed in vivo, should be made conveniently available for bioevaluation. We recently showed that selective acylation of allyl glucuronate is a promising method for the synthesis of these metabolites in good yield and with excellent β-anomeric selectivity. We now give fuller details of the allyl ester method and further report that benzyl glucuronate performs at least equally well in the acylation step, offering the advantage of very mild deprotection by catalytic transfer (or conventional) hydrogenation. Depending on the compatibility of other functional groups, as discussed below, this will be the method of choice for many acyl glucuronide syntheses. The value of the method is demonstrated in particular by the synthesis of several acyl glucuronides that are known metabolites of important drugs.

Synthesis of urine drug metabolites: Glucuronosyl esters of carboxymefloquine, indoprofen, (S)-naproxen, and desmethyl (S)-naproxen

A general procedure for the synthesis of 1-O-acyl-β-D-glucuronic acids using the benzyl 1-O-trichloroacetimidoyl-2,3,4-tri-O-benzyl-D- glucopyranuronate 6 as donor is exemplified by the synthesis of the urine metabolites of (S)-naproxen, desmethyl (S)-naproxen, indoprofen, and carboxymefloquine. The key intermediate benzyl 2,3,4-tri-O-benzyl-D- glucopyranuronate 5 is easily accessible in four steps (29%) from the peracetylated β-D-glucuronic acid 1. Copyright