Efficient access to bisphenol A metabolites: Synthesis of monocatechol, mono-<i>o-</i>quinone, dicatechol, and di-<i>o</i>-quinone of bisphenol A

Stack, Douglas E.; Mahmud, Bejan

doi:10.1080/00397911.2017.1390586

Cited by 10 publications

(7 citation statements)

References 24 publications

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“…23 Caution: IBX is explosive under impact if heated to more than 200 °C. BPAQ was made by IBX oxidation of BPA 16 with modifications to product isolation (see below). Deuterated NMR solvents were purchased from Cambridge Isotope (Andover, MA).…”

Section: ■ Experimental Proceduresmentioning

confidence: 99%

“…14,15 Recently we have developed a large-scale synthetic approach to the BPA metabolites, BPAQ, the di-o-quinone of BPA, the monocatechol of BPA, and the dicatechol of BPA. 16 new synthetic technique at hand, we sought to determine the major product(s) when BPAQ reacts with NAC and GSH. Scheme 2 shows the three possible conjugate addition products when BPAQ reacts with these sulfur nucleophiles.…”

Section: ■ Introductionmentioning

confidence: 99%

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Structural Identification and Kinetic Analysis of the in Vitro Products Formed by Reaction of Bisphenol A-3,4-quinone with N-Acetylcysteine and Glutathione

Stack

Conrad

Mahmud

2018

Chem. Res. Toxicol.

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Bisphenol A (BPA) has received considerable attention as an endocrine disrupting chemical and a possible substrate for genotoxic metabolites. BPA metabolism leads to formation of electrophilic o-quinones cable of binding to DNA and other endogenous nucleophiles. We have structurally identified the products resulting from the reaction of bisphenol A-3,4-quinone (BPAQ) with N-acetylcysteine (NAC) and glutathione (GSH). The major and minor isomers are both the result of 1,6-conjugate addition and are produced almost instantly in high yield. Reactions using 1.3 equiv of GSH showed the presence of a bis-glutathionyl adduct which was not observed using higher GSH concentration relative to BPAQ. NAC reactions with BPAQ showed no bis-N-acetylcysteinyl adducts. Stopped-flow kinetic analysis reveals the 1,6-conjugate additions to be reversible with a forward free energy of activation of 9.2 and 7.8 kcal/mol for the NAC and GSH reactions, respectively. The bimolecular forward rate constant at 19.4 °C was approximately three time faster for GSH compared to NAC, 1547 vs 496 M s. The free energy of activation for the reverse reactions were similar, 11.7 and 11.2 kcal/mol for NAC and GSH, respectively. We plan to use this model system to further explore the mechanism of adduct formation between sulfur nucleophiles and o-quinones and the resulting chemical properties of both NAC and GSH adducts.

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Section: ■ Experimental Proceduresmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Structural Identification and Kinetic Analysis of the in Vitro Products Formed by Reaction of Bisphenol A-3,4-quinone with N-Acetylcysteine and Glutathione

Stack

Conrad

Mahmud

2018

Chem. Res. Toxicol.

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“…BPF 3,4-quinone (BPFQ) was synthesized based on the one-pot reaction method reported by Stack and Mahmud . The oxidation of BPF to BPFQ by IBX was an effective approach to the production of o -quinones. , BPF (0.300 g or 1.498 mmol) was dissolved in a solvent mixture composed of CHCl 3 –CH 3 OH (3:2) at 0 °C and reacted with 1:1 equiv of IBX over a period of 2 h. The samples were shaken vigorously at 0 °C.…”

Section: Methodsmentioning

confidence: 99%

“…The oxidation of BPF to BPFQ by IBX was an effective approach to the production of o -quinones. , BPF (0.300 g or 1.498 mmol) was dissolved in a solvent mixture composed of CHCl 3 –CH 3 OH (3:2) at 0 °C and reacted with 1:1 equiv of IBX over a period of 2 h. The samples were shaken vigorously at 0 °C. The solution was then washed six times with 100 mL of a mixture consisting of 400 mL of 0.1 M phosphate buffer at pH 6.0, 200 mL of saline, and 50 g of sodium dithionite . The product was obtained after dryness with anhydrous sodium sulfate and spin-dried at room temperature. , 1 H NMR and 13 C NMR spectra of BPFQ were obtained from analyses by a JNM-ECZ400S/L spectrometer.…”

Section: Methodsmentioning

confidence: 99%

DNA and RNA Adducts Formation from 3,4-Quinone Metabolites of Bisphenol F

Wang

Cao

Yang

et al. 2021

Environ. Sci. Technol. Lett.

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Bisphenol F (BPF) has been widely used as the predominant substitute of bisphenol A to increase the thickness and durability of industrial materials such as epoxy resins and coatings. In this study, formation of deoxyribonucleoside/ribonucleoside adducts from quinone metabolites of BPF was investigated by using ultrahigh performance liquid chromatography coupled with Orbitrap high-resolution mass spectrometry. The results suggested that both deoxyribonucleosides and ribonucleosides could covalently bind to the chemosynthetic and biotransformed BPF-quinone. The exocyclic NH2 group and the N-7 of deoxyguanosine (dG) and deoxyadenosine (dA) could nucleophilically react with the deficient carbon C-6 from BPF-quinone to form two types of adducts, whereas the Michael addition occurred between the amino groups from guanosine (G), adenosine (A), and deoxycytidine (dC), as well as cytidine (C) and carbon C-6 from quinone. No adducts were detected between BPF-quinone and thymine (T) and uracil (U) because the two carbonyl groups near the N-1 from T and U increased the steric hindrance of the addition reaction. The formation of DNA and RNA adducts of BPF through its metabolic activation may provide important information for the investigation of BPF genotoxicity.

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“…For example, iodine(V) species, such as 2-iodoxybenzoic acid (IBX), are recognized as effective oxidants for a wide range of synthetic transformations . More specifically, the double oxidation of phenols by IBX or related iodine(V) reagents delivers ortho -quinones in a highly regioselective manner . However, to date, a notable limitation of iodine(V)-mediated phenol oxidation chemistry is that these transformations are typically restricted to electron-rich phenol substrates.…”

Section: Introductionmentioning

confidence: 99%

Oxidation of Electron-Deficient Phenols Mediated by Hypervalent Iodine(V) Reagents: Fundamental Mechanistic Features Revealed by a Density Functional Theory-Based Investigation

et al. 2021

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Hypervalent iodine (HVI) compounds are efficient reagents for the double oxidative dearomatization of electron-rich phenols to o-quinones. We recently reported that an underexplored class of iodine(V) reagents possessing bidentate bipyridine ligands, termed Bi(N)-HVIs, could dearomatize electron-poor phenols for the first time. To understand the fundamental mechanistic basis of this unique reactivity, density functional theory (DFT) was utilized. In this way, different pathways were explored to determine why Bi(N)-HVIs are capable of facilitating these challenging transformations while more traditional hypervalent species, such as 2-iodoxybenzoic acid (IBX), cannot. Our calculations reveal that the first redox process is the rate-determining step, the barrier of which hinges on the identity of the ligands bound to the iodine(V) center. This crucial process is composed of three steps: (a) ligand exchange, (b) hypervalent twist, and (c) reductive elimination. We found that strong coordinating ligands disfavor these elementary steps, and, for this reason, HVIs bearing such ligands cannot oxidize the electron-poor phenols. In contrast, the weakly coordinating triflate ligands in Bi(N)-HVIs allow for the kinetically favorable oxidation. It was identified that trapping in situ-generated triflic acid is a key role played by the bidentate bipyridine ligands in Bi(N)-HVIs as this serves to minimize the decomposition of the ortho-quinone product.

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Efficient access to bisphenol A metabolites: Synthesis of monocatechol, mono-o-quinone, dicatechol, and di-o-quinone of bisphenol A

Cited by 10 publications

References 24 publications

Structural Identification and Kinetic Analysis of the in Vitro Products Formed by Reaction of Bisphenol A-3,4-quinone with N-Acetylcysteine and Glutathione

Structural Identification and Kinetic Analysis of the in Vitro Products Formed by Reaction of Bisphenol A-3,4-quinone with N-Acetylcysteine and Glutathione

DNA and RNA Adducts Formation from 3,4-Quinone Metabolites of Bisphenol F

Oxidation of Electron-Deficient Phenols Mediated by Hypervalent Iodine(V) Reagents: Fundamental Mechanistic Features Revealed by a Density Functional Theory-Based Investigation

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