Glucuronide and sulfate conjugates of ICI 182,780, a pure anti-estrogenic steroid. Order of addition, catalysis and substitution effects in glucuronidation

Ferguson, John R.; Harding, John; Lumbard, Keith W.; Scheinmann, F.; Stachulski, Andrew V.

doi:10.1016/s0040-4039(99)02067-5

Cited by 21 publications

(16 citation statements)

References 8 publications

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“…An inverse addition, which means trichloroacetimidate 7 was added into the mixed solution of 2 phosphate and BF 3 ×Et 2 O, improved the yield to 52% from 21%. This result is consistent with the prior report for glucuronidation of other compounds [13] .…”

Section: Discussionsupporting

confidence: 94%

Identification of some benproperine metabolites in humans and investigation of their antitussive effect1

Zhong

Chen

et al. 2005

Acta Pharmacologica Sinica

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Aim: To identify 4 unknown metabolites of benproperine (BPP, 1) in human urine after a po dose, and to investigate the antitussive effect of monohydroxylate metabolites. Methods: The putative metabolite references were prepared using chemical synthesis. Their structures were identified using 1H and 13C nuclear magnetic resonance, and mass spectrometry. The metabolites in human urine were separated and assayed using liquid chromatography‐ion trap mass spectrometry (LC/MS/MS), and further confirmed by comparison of their mass spectra and chromatographic retention times with those of synthesized reference substances. The antitussive effects of metabolites were evaluated on coughs induced by 7.5% citric acid in conscious guinea pigs. Results: 1‐[1‐Methyl‐2‐[2‐(phenylmethyl)phenoxy]‐ethyl]‐4‐piperidinol (2), 1‐[1‐methyl‐2‐[2‐(phenylmethyl) phenoxy] ethyl]‐3‐piperidinol (3) and their glucuronides 4 and 5 were obtained from chemical synthesis. Four urinary metabolites in human urine showed peaks with the same chromatographic retention times and mass spectra in LC/MS/MS as synthetic substances 2, 3, 4 and 5. Phosphates of compounds 2 and 3 prolonged the latency of cough and reduced the number of coughs during the 3 min test using citric acid, but did not reduce the number of coughs during the 5 min immediately after the test in conscious guinea pigs. Conclusion: Compounds 2, 3, 4, and 5 were identified as the metabolites of BPP in human urine. Among them, compounds 2 and 3 are inactive in the antitussive effect.

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Section: Discussionsupporting

confidence: 94%

Identification of some benproperine metabolites in humans and investigation of their antitussive effect1

Zhong

Chen

et al. 2005

Acta Pharmacologica Sinica

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“…Glucuronidation of compounds with phenolic hydroxyl groups often utilizes methyl (2,3,4-tri- O -acetyl-D-glucopyranosyl trichloroacetimidate) uronate 6 , with activation of the coupling step by Lewis acids such as BF 3 ˑOEt 2 , TMSOTf or ZnCl 2 99,102,103,112–115 . Use of benzyl uronate counterpart 8 should facilitate the final release of the carboxylic acid function following hydrogenolysis under neutral conditions 116 .…”

Section: ■ Strategies For Chemical Synthesis Of Glucuronidated Flavonmentioning

confidence: 99%

Glucuronidated Flavonoids in Neurological Protection: Structural Analysis and Approaches for Chemical and Biological Synthesis

Docampo

Adiji

Wang

et al. 2017

J. Agric. Food Chem.

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Both plant and mammalian cells express glucuronosyltransferases that catalyze glucuronidation of polyphenols such as flavonoids and other small molecules. Oral administration of select polyphenolic compounds leads to the accumulation of the corresponding glucuronidated metabolites at μM and sub-μM concentrations in the brain, associated with amelioration of a range of neurological symptoms. Determining the mechanisms whereby botanical extracts impact cognitive wellbeing and psychological resiliency will require investigation of the modes of action of the brain-targeted metabolites. Unfortunately, many of these compounds are not commercially available. This article describes the latest approaches for the analysis and synthesis of glucuronidated flavonoids. Synthetic schemes include both standard organic synthesis, semi-synthesis, enzymatic synthesis and use of synthetic biology utilizing heterologous enzymes in microbial platform organisms.

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“…When acetyl protecting groups were used, orthoesters side-products were obtained, whereas with isobutyryl imidate, in “inverse mode”, the yield increased [ 26 ]. For example the glucuronation of estradiol derivative 65 with the imidate 55 gave the glucuronide 66 in 77% yield ( Scheme 16 ).…”

Section: Glucuronidationmentioning

confidence: 99%

“…A successful synthesis of the glucuronide metabolite 73 was performed using a N -acetylated Soraprazan 72 and tri-iso-butyrate trichloroacetamidate donor 55 [ 28 ] ( Scheme 18 ), avoiding the formation of orthoesters observed when using the analogous acetyl protected trichloroacetimidate donor [ 26 ].…”

Section: Glucuronidationmentioning

confidence: 99%

Synthesis of Glycosides of Glucuronic, Galacturonic and Mannuronic Acids: An Overview

Wadouachi

Kovensky

2011

Molecules

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Uronic acids are carbohydrates present in relevant biologically active compounds. Most of the latter are glycosides or oligosaccharides linked by their anomeric carbon, so their synthesis requires glycoside-bond formation. The activation of this anomeric center remains difficult due to the presence of the electron-withdrawing C-5 carboxylic group. Herein we present an overview of glucuronidation, mannuronidation and galacturonidation reactions, including syntheses of prodrugs, oligosaccharides and stereochemical aspects.

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Glucuronide and sulfate conjugates of ICI 182,780, a pure anti-estrogenic steroid. Order of addition, catalysis and substitution effects in glucuronidation

Cited by 21 publications

References 8 publications

Identification of some benproperine metabolites in humans and investigation of their antitussive effect1

Identification of some benproperine metabolites in humans and investigation of their antitussive effect1

Glucuronidated Flavonoids in Neurological Protection: Structural Analysis and Approaches for Chemical and Biological Synthesis

Synthesis of Glycosides of Glucuronic, Galacturonic and Mannuronic Acids: An Overview

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