Gas‐phase reactivity of 2‐hydroxy‐1,4‐naphthoquinones: a computational and mass spectrometry study of lapachol congeners

Vessecchi, Ricardo; Emery, Flávio da Silva; Galembeck, Sérgio E.; Lopes, Norberto P.

doi:10.1002/jms.3101

Cited by 27 publications

(48 citation statements)

References 48 publications

(64 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…37 Additionally, substituents at the C3 position—the 2-oxopropyl moieties in cercoquinones C and D—can influence the fragmentation of the quinone ring. 37–39 Mass fragmentation results for cercoquinones C and D are presented in detail in the Supporting Information.…”

Section: Resultsmentioning

confidence: 99%

Molecular Characterization of the Cercosporin Biosynthetic Pathway in the Fungal Plant Pathogen Cercospora nicotianae

Newman

Townsend

2016

J. Am. Chem. Soc.

View full text Add to dashboard Cite

Perylenequinones are a class of photoactivated polyketide mycotoxins produced by fungal plant pathogens that notably produce reactive oxygen species with visible light. The best-studied perylenequinone is cercosporin-a product of the Cercospora species. While the cercosporin biosynthetic gene cluster has been described in the tobacco pathogen Cercospora nicotianae, little is known of the metabolite's biosynthesis. Furthermore, in vitro investigations of the polyketide synthase central to cercosporin biosynthesis identified the naphthopyrone nor-toralactone as its direct product-an observation in conflict with published biosynthetic proposals. Here, we present an alternative biosynthetic pathway to cercosporin based on metabolites characterized from a series of biosynthetic gene knockouts. We show that nor-toralactone is the key polyketide intermediate and the substrate for the unusual didomain protein CTB3. We demonstrate the unique oxidative cleavage activity of the CTB3 monooxygenase domain in vitro. These data advance our understanding of perylenequinone biosynthesis and expand the biochemical repertoire of flavindependent monooxygenases.

show abstract

Section: Resultsmentioning

confidence: 99%

Molecular Characterization of the Cercosporin Biosynthetic Pathway in the Fungal Plant Pathogen Cercospora nicotianae

Newman

Townsend

2016

J. Am. Chem. Soc.

View full text Add to dashboard Cite

show abstract

“…It is important to define the fragmentation mechanism of protonated alkaloids under collision‐induced dissociation (CID) when we apply this mechanism in structural elucidation studies . In addition, it is essential to gather information about the reactive sites and the stability of ions by computational chemistry to support the fragmentation mechanism of a series of compounds . In the present investigation, we have combined MS analysis with computational chemistry to analyze erythrinian alkaloids.…”

Section: Introductionmentioning

confidence: 99%

Gas‐phase dissociation study of erythrinian alkaloids by electrospray ionization mass spectrometry and computational methods

et al. 2017

View full text Add to dashboard Cite

Alkaloids from plants of the genus Erythrina display important biological activities, including anxiolytic action. Characterization of these alkaloids by mass spectrometry (MS) has contributed to the construction of a spectral library, has improved understanding of their structures and has supported the proposal of fragmentation mechanisms in light of density functional calculations. In this study, we have used low-resolution and high-resolution MS analyses to investigate the fragmentation patterns of erythrinian alkaloids; we have employed the B3LYP/6-31+G(d,p) model to obtain their reactive sites. To suggest the fragmentation mechanism of these alkaloids, we have studied their protonation sites by density functional calculation, and we have obtained their molecular electrostatic potential map and their gas-phase basicity values. These analyses have indicated the most basic sites on the basis of the proton affinities of the nitrogen and oxygen atoms. The protonated molecules were generated by two major fragmentations, namely, neutral loss of CH OH followed by elimination of H O. High-resolution analysis confirmed elimination of NH by comparison with the losses of H and •CH . NH was eliminated from compounds that did not bear a substituent on ring C. The benzylic carbocation initiated the dissociation mechanism, and the first reaction involved charge transfer from a lone pair of electrons in the oxygen atoms. The second reaction consisted of ring contraction with loss of a CO molecule. The presence of hydroxy and epoxy groups could change the intensity or the occurrence of the fragmentation pathways. Given that erythrinian alkaloids are applied in therapeutics and are promising leads for the development of new drugs, the present results could aid identification of several analogues of these alkaloids in biological samples and advance pharmacokinetic studies of new plant derivatives based on MS and MS/MS analyses. Copyright © 2017 John Wiley & Sons, Ltd.

show abstract

“…The ESI‐MS/MS gas‐phase reactions are related with the ionization sites. The knowledge of protonation sites is a key step to elucidate the mechanisms of fragmentation occurring in the CID experiments in positive ion detection mode . ESI mechanisms remain unclear, and the gas‐phase or liquid‐phase parameters can contribute to interpret the relative occurrence of ions in the MS spectra .…”

Section: Resultsmentioning

confidence: 99%

Gas‐phase fragmentation of protonated piplartine and its fungal metabolites using tandem mass spectrometry and computational chemistry

et al. 2017

View full text Add to dashboard Cite

Piplartine, an alkaloid produced by plants in the genus Piper, displays promising anticancer activity. Understanding the gas-phase fragmentation of piplartine by electrospray ionization tandem mass spectrometry can be a useful tool to characterize biotransformed compounds produced by in vitro and in vivo metabolism studies. As part of our efforts to understand natural product fragmentation in electrospray ionization tandem mass spectrometry, the gas-phase fragmentation of piplartine and its two metabolites 3,4-dihydropiplartine and 8,9-dihydropiplartine, produced by the endophytic fungus Penicillium crustosum VR4 biotransformation, were systematically investigated. Proposed fragmentation reactions were supported by ESI-MS/MS data and computational thermochemistry. Cleavage of the C-7 and N-amide bond, followed by the formation of an acylium ion, were characteristic fragmentation reactions of piplartine and its analogs. The production of the acylium ion was followed by three consecutive and competitive reactions that involved methyl and methoxyl radical eliminations and neutral CO elimination, followed by the formation of a four-member ring with a stabilized tertiary carbocation. The absence of a double bond between carbons C-8 and C-9 in 8,9-dihydropiplartine destabilized the acylium ion and resulted in a fragmentation pathway not observed for piplartine and 3,4-dihydropiplartine. These results contribute to the further understanding of alkaloid gas-phase fragmentation and the future identification of piplartine metabolites and analogs using tandem mass spectrometry techniques. Copyright © 2017 John Wiley & Sons, Ltd.

show abstract

Gas‐phase reactivity of 2‐hydroxy‐1,4‐naphthoquinones: a computational and mass spectrometry study of lapachol congeners

Cited by 27 publications

References 48 publications

Molecular Characterization of the Cercosporin Biosynthetic Pathway in the Fungal Plant Pathogen Cercospora nicotianae

Molecular Characterization of the Cercosporin Biosynthetic Pathway in the Fungal Plant Pathogen Cercospora nicotianae

Gas‐phase dissociation study of erythrinian alkaloids by electrospray ionization mass spectrometry and computational methods

Gas‐phase fragmentation of protonated piplartine and its fungal metabolites using tandem mass spectrometry and computational chemistry

Contact Info

Product

Resources

About