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|Title:||Continuous flow fast atom bombardment and electrospray ionization mass spectrometry in natural products research|
|Doctoral Committee Chair(s):||Rinehart, Kenneth L., Jr.|
|Department / Program:||Chemistry, Analytical|
|Degree Granting Institution:||University of Illinois at Urbana-Champaign|
|Abstract:||Continuous flow fast atom bombardment (CF-FAB) has been applied as a liquid chromatography/mass spectrometry (LC/MS) and liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) interface in natural products research. Initial studies concentrated on characterization of the interface, optimization of operational parameters and sensitivity assessment. Using a CF-FAB interface, femtomole quantities of different classes of compounds were detected, which is two orders of magnitude more sensitive than by standard FAB. Later, CF-FAB was applied to the analysis of didemnin, streptovaricin, and ecteinascidin mixtures in isocratic and/or gradient modes.
The first application led to the discovery of acyclo-desHIP-didemnin A in a mixture of didemnins, cyclic peptides of potent antitumor and antiviral activity. Although related to didemnins, the linear peptide was biologically inactive. The second application project involved streptovaricins, secondary metabolites of Streptomyces spectabilis. In the streptovaricin mixture, besides streptovaricins, protostreptovaricins III and IV were detected by LC/CF-FABMS. The presence of protostreptovaricins in the streptovaricin complex confirmed the biosynthetic pathway proposed for streptovaricin C. Even though these precursors were known previously, they were not observed as components of the mixture by standard FABMS.
When ecteinascidins were analyzed by LC/CF-FABMS, the most significant difference was the amount of structural information generated in the low mass range in comparison to the standard FAB spectra. The hydrates of structurally significant fragment ions were observed when the background was subtracted. The use of a CF-FAB interface was extended to on-line high resolution mass measurements of different components in the mixture. Mass measurements were within the range of acceptable error. On-line LC/CF-FABMS/MS was performed on the ecteinascidin mixture using B/E linked scans. Observed ions were then classified as group-characteristic or compound-specific.
Finally, CF-FAB was compared to electrospray ionization (ESI) as an LC/MS and LC/MS/MS interface with respect to sensitivity and structural information. In the selected ion chromatogram mode, the sensitivity of CF-FAB is comparable to that of LC/ESIMS. However, identification of unknowns is more feasible by LC/ESIMS than by LC/CF-FABMS. Also, the daughter ion mass spectra can be produced even on trace amounts by LC/ESIMS/MS and are of better quality than by LC/CF-FABMS/MS. In LC/ESIMS/MS, similar structural information is obtained; however, the main difference is the relative intensities of the fragment ions. Several new ecteinascidins were observed by LC/ESIMS. Their structures are proposed on the basis of LC/ESIMS/MS data.
|Rights Information:||Copyright 1995 Janota, Katarzyna|
|Date Available in IDEALS:||2011-05-07|
|Identifier in Online Catalog:||AAI9543611|