Synthesis of 1-β-O-acyl glucuronides of diclofenac, mefenamic acid and (S)-naproxen by the chemo-selective enzymatic removal of protecting groups from the corresponding methyl acetyl derivatives

Baba, Akiko; Yoshioka, Takayuki

doi:10.1039/b608755h

Cited by 32 publications

(33 citation statements)

References 41 publications

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“…The rearranged compound 10 was formed with 12 %y ield and 30 %o f the starting material 8 could be recovered. Finally, 9b was transformed into the desired aldosterone-18-b-glucuronide 3 by treatment with PLE esterase [17] to give the corresponding acid 20 followed by reaction with lipase WG [18] to remove the acetyl moieties avoiding anyi somerization at C-17 with 24 % overall yield.…”

Section: Resultsmentioning

confidence: 99%

Aldosterone Glucuronide, an Important Biomarker: Synthesis and Structure Elucidation of Novel Isomers

Guha

Senthilkumar

Voß

et al. 2020

Chemistry A European J

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Aldosterone 1 is am ineralocorticoid, it has great influence on the blood pressure and its glucuronide is an important marker for the detection of several diseases.H ere, we describe the chemical synthesis of different aldosterone-18-and 20-glucuronides. Reaction of trimethylsilyl 2,3,4-triacetyl-1-b-glucuronic acid methyl ester 5b and aldosterone diacetate 11 in the presence of TMSOTf gave the 18-a-glucuronide 9a.The 18-b-glucuronide 15 b and the 20-b-glucuronide 16 b could be obtained by reaction of methyl 2,3,4-triO -isobutyryl-1a-glucuronatet richloroacetimidate 14 and aldosterone 21-acetate 8 in the presence of TMSOTf or BF 3 •OEt 2 .F inally,r eaction of aldosterone 21-acetate 8 and methyl 2,3,4-triacetyl-1a-glucuronate trichloroacetimidate 19 in the presence of TMSOTf gave the corresponding methyl 18-b-triacetylglucuronate 9b,w hichw as transformed into the desired aldosterone-18-b-glucuronide 3 by two enzymatic transformations.

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Section: Resultsmentioning

confidence: 99%

Aldosterone Glucuronide, an Important Biomarker: Synthesis and Structure Elucidation of Novel Isomers

Guha

Senthilkumar

Voß

et al. 2020

Chemistry A European J

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“…β‐Glucuronidase (β‐Glu) stands out as an enzyme with extensive prior characterization and availability of the substrates (prodrugs) to yield therapeutics with a wide spectrum of action, many of which are available commercially. This includes drugs to treat cancer, inflammation, hypertension, viral diseases, as well as agents for imaging – all due to the fact that glucuronides are natural metabolic products of commercial drugs and therefore undergo stringent analysis for regulatory approval and to define the scope and utility of therapies. The above cited literature reports describe examples of glucuronide substrates to yield therapeutic molecules to treat a magnitude of diseases as well as imaging reagents and this illustrates that the same enzyme, β‐Glu, can serve to produce a panel of diverse products, independent of their structure, function, solubility and charge.…”

Section: Introductionmentioning

confidence: 99%

Biocatalytic Polymer Coatings: On‐Demand Drug Synthesis and Localized Therapeutic Effect under Dynamic Cell Culture Conditions

Fejerskov

Jensen

Teo

et al. 2013

Small

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Biocatalytic surface coatings are prepared herein for localized synthesis of drugs and their on-demand, site-specific delivery to adhering cells. This novel approach is based on the incorporation of an enzyme into multilayered polymer coatings to accomplish enzyme-prodrug therapy (EPT). The build-up of enzyme-containing multilayered coatings is characterized and correlations are drawn between the multilayer film assembly conditions and the enzymatic activity of the resulting coatings. Therapeutic effect elicited by the substrate mediated EPT (SMEPT) strategy is investigated using a prodrug for an anticancer agent, SN-38. The performance of biocatalytic coatings under flow conditions is investigated and it is demonstrated that EPT allows synthesizing the drugs on-demand, at the time desired and in a controllable amount to suit particular applications. Finally, using cells cultured in sequentially connected flow chambers, it is demonstrated that SMEPT affords a site-specific drug delivery, that is, exerts a higher therapeutic effect in cells adhering directly to the biocatalytic coatings than in the cells cultured "downstream". Taken together, these data illustrate biomedical opportunities made possible by engineering tools of EPT into multilayered polymer coatings and present a novel, highly versatile tool for surface mediated drug delivery.

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“…Purification by HPLC led to the isolation of the methyl ester of mefenamic acid [13]. The facile hydrolysis of acyl glucosides and glucuronides is well documented [5,14].…”

mentioning

confidence: 99%

Biotransformation of Mefenamic Acid by Cell Suspension Cultures of Solanum Mammosum

Surodjo

Salim

Suciati

et al. 2008

Natural Product Communications

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Five biotransformation products, mefenamic acid-7- O-β-D-glucopyranosyl ester (2), mefenamic acid-7- O-β-D-(β-1,6- O-D-glucopyranosyl)-glucopyranosyl ester (3), mefenamic acid-7- O-β-D-(β-1,2- O-D-glucopyranosyl)-glucopyranosyl ester (4), mefenamic acid-7- O-β-D-(β-1,6- O-D-glucopyranosyl)-2-glucopyranose ester (5), and mefenamic acid-7- O-α-D-(β-1,6- O-D-glucopyranosyl)-2-glucopyranose ester (6) were isolated from cell suspension cultures of Solanum mammosum following administration of the therapeutic agent mefenamic acid (1). The structures of all new compounds were elucidated on the basis of their NMR and mass spectrometric data.

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Synthesis of 1-β-O-acyl glucuronides of diclofenac, mefenamic acid and (S)-naproxen by the chemo-selective enzymatic removal of protecting groups from the corresponding methyl acetyl derivatives

Cited by 32 publications

References 41 publications

Aldosterone Glucuronide, an Important Biomarker: Synthesis and Structure Elucidation of Novel Isomers

Aldosterone Glucuronide, an Important Biomarker: Synthesis and Structure Elucidation of Novel Isomers

Biocatalytic Polymer Coatings: On‐Demand Drug Synthesis and Localized Therapeutic Effect under Dynamic Cell Culture Conditions

Biotransformation of Mefenamic Acid by Cell Suspension Cultures of Solanum Mammosum

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