Global 2-Acetyl Furan Market Outlook 2017-2022

Previous studies indicated that metabolites 4 and 5 were significant urinary metabolites of furan (, ). A likely precursor to these metabolites is a cysteine-BDA-lysine crosslink 6 (). In addition to acetylation, both amino acid residues are predicted to undergo other pathways of biotransformation. We explored the ability of both the cysteine and the lysine residues of 6 to undergo further metabolism. Compound 6, itself, was not observed as a urinary metabolite of furan (data not shown).

Efficient synthesis of cytotoxic quinones: 2‐Acetyl…

 2-acetyl-5-methylfuran Aromatic/ Heterocyclic Aldehyde Chalcone derivative
Photo provided by
Flickr

Efficient synthesis of cytotoxic quinones: 2-Acetyl-4H ..

Since metabolites 9 and 13 were urinary metabolites of furan, it is also likely that the N-acetylcysteine precursors to 9, 12 and 13 are also present in the urine of furan-treated rats. Oxidation of N-acetyl-S-[1-(5-amino-5-carboxypentyl)-1H-pyrrol-3-yl]-L-cysteine (14) would lead to 12 (). Compound 14 was detected as a metabolite of furan in hepatocytes (). As with 12, metabolite 14 was not detected when the urine was analyzed with an ion trap mass spectrometer. However, this metabolite was observed when the urine was re-analyzed by tandem mass spectrometry with a constant neutral loss scan of 129 (C5H7NO3). This is a characteristic neutral loss observed in N-acetylcysteine conjugates () (). This metabolite co-eluted with the synthetic standard 14 (). As with metabolite 12, the reasons for the detection difficulties require further investigation but may involve the presence of co-eluting chemicals that suppress the ionization of 14 (data not shown).

Global 2-Acetyl Furan Market Outlook 2017-2022, …

As demonstrated in the RLH incubations, metabolite 12 is a precursor of metabolites 9 and 13. Metabolite 12 was not observed when the urine from furan-treated rats was analyzed by LC-MS/MS using an ion trap mass spectrometer even when operated in selected ion monitoring mode. Since all compounds containing the N-acetylcysteine sulfoxide moiety (5, 9, 13 and 12) lost 147 Da (C5H9N05) as a neutral fragment, the urine samples were re-analyzed by tandem mass spectrometry with a constant neutral loss scan of 147. When this approach was employed, a peak was observed with a retention time comparable to synthetic 12 (). There was a corresponding 4 Da increase in the metabolite (m/z 378) detected in the urine from [13C4]furan-treated rats (). Similar data was obtained when the neutral loss of 95 (C2H9NO3) was monitored (data not shown). The identity of the metabolite was also verified by coelution with synthetic standard 12 (). Further studies will be required to determine why this compound was so difficult to detect. Preliminary studies indicate that co-eluting materials in the urine dramatically interfere with the detection of 12 (data not shown).

A selective method for the synthesis of 2-(bromoacetyl)-5-methylfuran by the bromination of 2-acetyl-5-methylfuran with bromine was developed.
Photo provided by
Flickr

Procedure for Synthesis of chalcones of 2-Acetyl-5 ..

A selective method for the synthesis of 2-(bromoacetyl)-5-methylfuran by the bromination of 2-acetyl-5-methylfuran with bromine was developed.">

3-Acetyl-2,5-dimethylfuran | CAS 10599-70-9 | SCBT - …

LC-MS/MS analysis of the urine from furan-treated rats did not display a peak at m/z 285 with a retention time similar to 7 (data not shown). A peak was observed at m/z 301 in [12C4]furan-treated rat urine and at m/z 305 in [13C4]furan-treated rat urine with a retention time similar to 8 (47.7 min, ). The metabolite co-eluted with the synthetic standard and had an identical daughter ion spectrum ( and ). In addition, high resolution MS analysis indicated that the metabolite had the expected exact mass for compound 8 ().

10/12/2017 · Synthesis of Furan Derivatives ..

Collectively, these metabolites indicate that the formation of cross-link 6 represents a significant biotransformation pathway for furan in vivo. There are multiple sources for this compound. Studies in hepatocytes indicate that a GSH-BDA-lysine cross-link is a metabolite of furan (). It is formed when BDA reacts with GSH and the subsequent conjugate reacts with either free or protein-bound lysine residues. Enzymatic processing of the glutathione moiety by γ-glutamyltranspeptidase and cysteinyl-glycine dipeptidase or aminopeptidase M yields 6 (). An alternative source of 6 is degraded protein-protein cysteine-lysine crosslinks. Consistent with the proposal that 6 is derived from degraded protein adducts is the observation that approximately 10% of a 8 mg/kg dose of [14C]furan remained covalently associated with liver proteins 24 h post exposure (). Our observations indicate that a portion of these protein adducts are GSH- or protein cysteinyl-BDA-lysine crosslinks. Therefore, any of the nine identified urinary metabolites could be markers for the activation of furan to protein reactive metabolites. Metabolites of 4, 5 and 9 were the easiest to detect in urine of furan-treated rats (), indicating that they may be good targets for human biomarker development.