Gas‐phase fragmentation reactions of protonated benzofuran‐ and dihydrobenzofuran‐type neolignans investigated by accurate‐mass electrospray ionization tandem mass spectrometry

Dias, Herbert Júnior; Baguenard, Manon; Crevelin, Eduardo José; Palaretti, Vinicius; Gates, Paul J.; Vessecchi, Ricardo; Crotti, Antônio Eduardo Miller

doi:10.1002/jms.4304

Cited by 10 publications

(23 citation statements)

References 51 publications

(92 reference statements)

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“…Studies report that fragmentation reactions using ESI-MS are revealed as a significant tool for structural characterization and elucidation of synthetic and natural compounds. [10][11][12][13] The technique has been extensively used for phenolic acids analysis, though studies dedicated to these compounds' fragmentation are still scarce. Martens et al 14 studied the ferulic acid fragmentation by infrared multiple-photon dissociation spectroscopy (IRMPD) and identified that protonated ferulic acid produces three ionic fragments (m/z 177, 149 and 163) and exhibit characteristic losses of CO and H 2 O. Kuhnert et al 15 report the use of liquid chromatography coupled in tandem to the mass spectrometer (LC-MS/MS) to easily distinguish eight regioisomers of ferulic acid by direct spectra comparison or rational fragmented ions probing.…”

Section: Introductionmentioning

confidence: 99%

Structural Study of Phenolic Acids by Triple Quadrupole Mass Spectrometry with Electrospray Ionization in Negative Mode and H/D Isotopic Exchange

Sinosaki

Tonin

Ribeiro

et al. 2020

J. Braz. Chem. Soc.

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This work reports the theoretical and experimental study of fragmentation reactions in the gas phase of five phenolic acids using triple quadrupole mass spectrometry by electrospray ionization in negative ionic mode, as well as the isotope exchange experiments. MS/MS spectra were analyzed to suggest the fragmentation mechanisms, while theoretical calculations at the theory level B3LYP/6-311+G** were performed to expose the proposed mechanisms viability for this class of compounds. As expected, compounds with aromatic methoxy substitution presented •CH 3 radical elimination as the principal fragmentation pathway, forming dystonic ions. Compounds without methoxy substituents dissociate with higher energies losing the CO 2 , CO and H 2 O. The isotopic marking experiments indicated the exchange of hydrogens by deuterases in the hydroxyl protons, which corroborates with the proposed mechanisms.

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Section: Introductionmentioning

confidence: 99%

Structural Study of Phenolic Acids by Triple Quadrupole Mass Spectrometry with Electrospray Ionization in Negative Mode and H/D Isotopic Exchange

Sinosaki

Tonin

Ribeiro

et al. 2020

J. Braz. Chem. Soc.

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“…The importance of determining the protonation site in gas‐phase fragmentation studies under CID conditions has recently been discussed …”

Section: Resultsmentioning

confidence: 99%

“…As part of our ongoing project on the gas‐phase fragmentation reactions of biologically active synthetic and natural compounds, and given the scarcity of ESI‐MS/MS data of MKCs, here we investigate the gas‐phase fragmentation pathways of selected curcuminoids by ESI‐MS/MS combined with thermochemical data obtained at the B3LYP/6‐31+G(d) level of theory.…”

Section: Introductionmentioning

confidence: 99%

Electrospray ionization tandem mass spectrometry of monoketone curcuminoids

Vieira

Orenha

Crevelin

et al. 2020

Rapid Comm Mass Spectrometry

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Rationale Although monoketone curcuminoids (MKCs) have been largely investigated due to their biological activities, data on the gas‐phase fragmentation reactions of protonated MKCs under collision‐induced dissociation (CID) conditions are still scarce. Here, we combined electrospray ionization tandem mass spectrometry (ESI‐MS/MS) data, multiple‐stage mass spectrometry (MSn), deuterium exchange experiments, accurate‐mass data, and thermochemical data estimated by computational chemistry to elucidate and to rationalize the fragmentation pathways of eleven synthetic MKCs. Methods The MKCs were synthesized by Claisen‐Schmidt condensation under basic (1–9) or acidic (10–11) conditions. ESI‐CID‐MS/MS analyses and deuterium‐exchange experiments were carried out on a triple quadrupole mass spectrometer. MSn analyses on an ion trap mass spectrometer helped to elucidate the fragmentation pathways. Accurate‐mass data and thermochemical data, obtained at the B3LYP/6–31+G(d,p) level of theory, were used to support the ion structures. Results The most intense product ions were the benzyl ions ([C7H2R1R2R3R4R5]+) and the acylium ions ([M + H − C8H3R1R2R3R4R5]+), which originated directly from the precursor ion as a result of two competitive hydrogen rearrangements. Product ions [M + H – H2O]+ and [M + H − C6HR1R2R3R4R5]+, which are formed after Nazarov cyclization, were also common to all the analyzed compounds. In addition, •Br and •Cl eliminations were diagnostic for the presence of these halogen atoms at the aromatic ring, whereas •CH3 eliminations were useful to identify the methyl and methoxy groups attached to this same ring. Nazarov cyclization in the gas phase occurred for all the investigated MKCs and did not depend on the presence of the hydroxyl group at the aromatic ring. However, the presence and the position of a hydroxyl group at the aromatic rings played a key role in the Nazarov cyclization mechanism. Conclusions Our results reinforce some aspects of the fragmentation pathways previously published for 1,5‐bis‐(2‐methoxyphenyl)‐1,4‐pentadien‐3‐one and 1,5‐bis‐(2‐hydroxyphenyl)‐1,4‐pentadien‐3‐one. The alternative fragmentation mechanism proposed herein can explain the fragmentation of a wider diversity of monoketone curcuminoids.

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“…The dihydrobenzofuran neolignans (DBNs) 1 and 2, which were used as standards, were synthesized by oxidative coupling of methyl p-coumarate (I) and methyl ferulate (II), respectively, in the presence of silver(I) oxide, as oxidant, as reported previously (Scheme 2). 4,7,11,16 Methyl p-coumarate (I) was obtained from coumaric acid (CA, 3.0 g, 18.3 mmol), which was dissolved in 30 mL of methanol in a 100-mL round-bottom flask, followed by addition of 1 mL of sulfuric acid. Methyl ferulate (II) was synthesized from ferulic acid (FA, 3.0 g, 15.4 mmol), which was dissolved in 180 mL of methanol in a 500-mL round-bottom flask, followed by addition of 3 mL of sulfuric acid.…”

Section: Synthesis Of the Dihydrobenzofuran Neolignans 1 Andmentioning

confidence: 99%

“…Synthesis of the dihydrobenzofuran neolignans 1 and 2 by silver(I)-oxide oxidative coupling of methyl p-coumarate (I) and methyl ferulate (II), respectively. 4,7,11,16 Methyl p-coumarate (I): 1…”

Section: Synthesis Of the Dihydrobenzofuran Neolignans 1 Andmentioning

confidence: 99%

Optimization of the Reaction Conditions for the Synthesis of Dihydrobenzofuran Neolignans

Dias¹,

Rodrigues²,

Crotti³

2020

Preprint

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We have optimized the experimental conditions for the silver(I)-promoted oxidative coupling of methyl p-coumarate (I) and methyl ferulate (II), which is the most frequently used methodology to synthesize the bioactive dihydrobenzofuran neolignans 1 ((±)-trans-dehydrodicoumarate dimethyl ester) and 2 ((±)-trans-dehydrodiferulate dimethyl ester). Most of the tested conditions affected the conversion (i.e., the consumption of I and II) and the selectivity (i.e., the percentage of I and II that was converted into 1 and 2, respectively), so the optimized conditions were the conditions that afforded the best balance between conversion and selectivity. Silver(I) oxide (0.5 eq) is the most efficient oxidant agent amongst the silver(I) reagents that were tested to convert methyl esters I and II into compounds 1 and 2, respectively. Acetonitrile, which has not yet been reported as a solvent for this reaction, provided the best balance between conversion and selectivity, besides being “greener” than other solvents that are more often employed (e.g., dichloromethane and benzene). Under the optimized conditions, the reaction time decreased from 20 h to 4 h without significantly impacting the conversion and selectivity. However, the relation between the results obtained by adding a radical initiator (AIBN) or a radical inhibitor (isoquinoline) and the previously reported involvement of radical intermediate species in the silver(I)-promoted oxidative coupling of I and II is not clear and deserves further investigation.

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Gas‐phase fragmentation reactions of protonated benzofuran‐ and dihydrobenzofuran‐type neolignans investigated by accurate‐mass electrospray ionization tandem mass spectrometry

Cited by 10 publications

References 51 publications

Structural Study of Phenolic Acids by Triple Quadrupole Mass Spectrometry with Electrospray Ionization in Negative Mode and H/D Isotopic Exchange

Structural Study of Phenolic Acids by Triple Quadrupole Mass Spectrometry with Electrospray Ionization in Negative Mode and H/D Isotopic Exchange

Electrospray ionization tandem mass spectrometry of monoketone curcuminoids

Optimization of the Reaction Conditions for the Synthesis of Dihydrobenzofuran Neolignans

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