Structural elucidation studies of erythromycins by electrospray tandem mass spectrometry II

Kearney, Gordon C.; Gates, Paul J.; Leadlay, Peter F.; Staunton, James; Jones, Raymond C. F.

doi:10.1002/(sici)1097-0231(19990830)13:16<1650::aid-rcm693>3.0.co;2-8

Cited by 29 publications

(28 citation statements)

References 12 publications

(9 reference statements)

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“…Protonated erythromycin B displays one less loss of water than erythromycin A in both the IRMPD and CAD spectra ( Figure 4), implying that the C-12 hydroxyl accounts for this extra step of dehydration in protonated erythromycin A. Protonated oleandomycin dissociates by the loss of the hexapyranose moiety in both the IRMPD and CAD spectra (formation of m/z 544), loss of both sugars (formation of m/z 387), and by formation of the desosamine ion (m/z 158) (IRMPD only). The absence of dehydration, a loss that was significant for both protonated erythromycin A and B, is accounted for by the lack of a hydroxyl group at C-6 [5]. Apparently the C-11 hydroxyl group is not a viable route for dehydration in these macrolides.…”

Section: Protonated Macrolides and Analogsmentioning

confidence: 96%

“…The clinical testing of these erythromycin analogs for bacteriostatic potential, possible human toxicity, and pharmacokinetics requires effective analytical techniques. Mass spectrometry has been utilized in several recent studies aimed at identifying the structures and fragmentation pathways of macrolide antibiotics [3][4][5][6][7][8][9]. For example, Gross and co-workers used fast atom bombardment (FAB) to create both protonated and alkali metal cationized species of erythromycin A, megalomicin A, desmycosin, megalalosamine, and tylosin, followed by CAD for structural characterization [3].…”

mentioning

confidence: 99%

“…They noted that the protonated macrolides gave fragmentation patterns that lacked mid-range fragment ions, whereas the alkali metal cationized species gave a greater variety of fragment ions. Gates et al used isotopic labeling to determine the origin of the initial water loss from protonated erythromycin [4,5]. For these studies, electrospray ionization (ESI) was used to introduce samples into either a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer (for accurate mass measurements), a quadrupole-time-offlight (Q-TOF) instrument, or a quadrupole ion trap for MS/MS experiments.…”

mentioning

confidence: 99%

“…For example, protonated macrolides typically lose water molecules in succession as the dominant dissociation pathways [5]. Another recognized feature of the dissociation behavior of protonated macrolides is their tendency to lose their sugar functional groups while the large, flexible macrolide ring remains largely intact.…”

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confidence: 99%

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Characterization of erythromycin analogs by collisional activated dissociation and infrared multiphoton dissociation in a quadrupole ion trap

Crowe

Brodbelt

Goolsby

et al. 2002

J. Am. Soc. Mass Spectrom.

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The effectiveness of two activation techniques, collision activated dissociation (CAD) and infrared multiphoton dissociation (IRMPD), is compared for structural characterization of protonated and lithium-cationized macrolides and a series of synthetic precursors in a quadrupole ion trap (QIT). Generally, cleavage of the glycosidic linkages attaching the sugars to the macrolide ring and water losses constitute the major fragmentation pathways for most of the protonated compounds. In the IRMPD spectra, a diagnostic fragment ion assigned as the desosamine ion is a dominant ion that is not observed in the CAD spectra because of the higher m/z limit of the storage range required during collisional activation. Activation of the lithium-cationized species results in new diagnostic fragmentation pathways that are particularly useful for confirming the identities of the protecting groups in the synthetic precursors. Multi-step IRMPD allows mapping of the fragmentation genealogies in greater detail and supports the proposed structures of the fragment ions. (J Am Soc Mass Spectrom 2002, 13, 630 -649)

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Section: Protonated Macrolides and Analogsmentioning

confidence: 96%

mentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Characterization of erythromycin analogs by collisional activated dissociation and infrared multiphoton dissociation in a quadrupole ion trap

Crowe

Brodbelt

Goolsby

et al. 2002

J. Am. Soc. Mass Spectrom.

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“…We therefore also performed fragmentation analysis on acetate starter EB (Ac-EB) (Structure 3), to investigate whether fragments containing the starter acid could be pinpointed on the fragmentation pathway. Previous MS-MS studies [11,12] had achieved this using erythromycin A analogs with different starter acids incorporated.…”

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confidence: 99%

Structural elucidation studies on 14- and 16-membered macrolide aglycones by accurate-mass electrospray sequential mass spectrometry

Roddis

Gates

Roddis

et al. 2002

J. Am. Soc. Mass Spectrom.

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Collision induced dissociation sequential mass spectrometry was used to investigate the fragmentation of the heptaketide macrolide aglycones, 6-deoxyerythronolide B (6-dEB), erythronolide B (EB), and acetate-starter EB (Ac-EB). The fragmentations of two previously reported octaketide analogs produced by "stuttering" of the erythromycin polyketide synthase, stuttered-6-dEB and acetate-starter stuttered-6-dEB were also studied. The accuracy with which the mass of each fragment was measured allowed it to be attributed to an unambiguous formula. Most of the experiments were repeated using samples dissolved in deuterated solvents. These data were then used to deduce plausible fragmentation pathways of the five compounds which were shown to have a high degree of similarity. Preliminary fragmentation analysis of a novel octaketide analog was performed and the structure was predicted as stuttered EB. Subsequent scale-up of the bacterial fermentations, followed by isolation and characterization by nuclear magnetic resonance spectroscopy confirmed this prediction. Further fragmentation experiments were then performed on this compound, which provided further evidence of the similarity of the fragmentation schemes. These results demonstrate the utility of collision induced dissociation sequential mass spectrometry analysis in the preliminary screening of bacterial fermentations for new polyketides. These studies were performed by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. (J Am Soc Mass Spectrom 2002, 13, 862-874)

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Structural elucidation studies of polyketide tetrasubstituted δ-lactones by gas chromatography/tandem mass spectrometry and electrospray mass spectrometry

Weissman

Kearney

Leadlay

et al. 1999

Rapid Commun. Mass Spectrom.

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A series of tetrasubstituted polyketide delta-lactones were used to evaluate whether gas chromatography/tandem mass spectrometry (GC/MS/MS) and electrospray mass spectrometry (ESI-MS) are useful techniques for probing the structure and stereochemistry of such highly functionalised molecules. Analyses were performed with two commercially available mass spectrometers: a Finnigan/MAT GCQ instrument (CI source) and a Q-TOF Hybrid quadrupole time-of-flight instrument (ESI source). The analyses revealed that a range of variation in the structure and stereochemistry of the lactones did not affect the fragmentation pathway common to these molecules. By accurate mass determination (ESI-MS), the first two fragmentations were assigned to losses of water. Although it was anticipated that the initial dehydration would include the hydroxyl group at the 3-position of the lactones, evidence from deuterium- and (18)O-labelling studies suggests that the losses of water instead involve the oxygen atoms in the ester bond. Attempts to identify further the structures of daughter ions by GC/MS/MS were complicated by extensive rearrangements and non-specific hydrogen/deuterium migrations within the lactones. Together, these results illustrate the limitations of mass spectrometry in the structural elucidation of complex molecules. Copyright 1999 John Wiley& Sons, Ltd.

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Structural elucidation studies of erythromycins by electrospray tandem mass spectrometry II

Cited by 29 publications

References 12 publications

Characterization of erythromycin analogs by collisional activated dissociation and infrared multiphoton dissociation in a quadrupole ion trap

Characterization of erythromycin analogs by collisional activated dissociation and infrared multiphoton dissociation in a quadrupole ion trap

Structural elucidation studies on 14- and 16-membered macrolide aglycones by accurate-mass electrospray sequential mass spectrometry

Structural elucidation studies of polyketide tetrasubstituted δ-lactones by gas chromatography/tandem mass spectrometry and electrospray mass spectrometry

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