Mass spectrometry carbohydrate fragmentation

Harvey, D.J. (2000) Electrospray Mass Spectrometry and Fragmentation of n-linked Carbohydrates Derivatized at the Reducing Terminus. J. Am. Soc. Mass Spectrom. 11 900-915. 

Harvey DJ. Electrospray mass spectrometry and fragmentation of n-linked carbohydrates derivatized at the reducing terminus. J Am Soe Mass Speetrom. 2000 11 900-95. 

A number of reviews of mass spectra of carbohydrates have been published from which references to the original papers are available (4, 9, 11, 24, 26). The application of mass spectrometry to this field was initially limited by the relatively low volatility of free carbohydrates and by the complex spectra obtained from some derivatives. These limitations have been partially overcome by new inlet techniques and by pioneering studies on classes and derivatives in order to understand the characteristic fragmentations and rearrangements of the molecular ions of a wide range of carbohydrates. 

In principle, mass spectrometry is not suitable to differentiate enantiomers. However, mass spectrometry is able to distinguish between diastereomers and has been applied to stereochemical problems in different areas of chemistry. In the field of chiral cluster chemistry, mass spectrometry, sometimes in combination with chiral chromatography, has been extensively applied to studies of proton- and metal-bound clusters, self-recognition processes, cyclodextrin and crown ethers inclusion complexes, carbohydrate complexes, and others. Several excellent reviews on this topic are nowadays available. A survey of the most relevant examples will be given in this section. Most of the studies was based on ion abundance analysis, often coupled with MIKE and CID ion fragmentation on MS " and FT-ICR mass spectrometric instruments, using Cl, MALDI, FAB, and ESI, and atmospheric pressure ionization (API) methods. 

Mass spectrometry of carbohydrates has become of interest, and offers potential for the identification of naturally occurring carbohydrates.254 This method may also be applicable in analyzing fragmentation products of polyglycoses. 

Application of mass spectrometry to carbohydrate derivatives has been reviewed in this Series. Although no example of its application to sugar sulfonates was cited, such experiments have undoubtedly been performed samples having very low volatility may be examined after direct introduction into the ion-source chamber. Sulfonates of 6-chloro-6-deoxy sugars were first identified in this way, and interpretation of the mass spectra was aided by the presence of fragments containing C1 and C1. 

The application of electron-impact mass spectrometry (e.i.m.s.) to carbohydrate compounds has been discussed in this Series by Kochetkov and Chizhov. The presence of the 2-acetamido-N-(L-aspart-4-oyl)-2-deoxy-)3-D-glucopyranosylamine (11), carbohydrate-peptide linkage in N-glycoproteins was demonstrated by e.i.m.s. The fragmentation patterns of synthetic glycopeptides containing an N-(L-aspart-4-oyl)glyco-... 

Much of the earlier work on the mass spectrometry of carbohydrates was discussed in this Series by Kochetkov and Chizhov, and the same authors have presented certain practical aspects of the technique. Hanessian described the application of mass spectrometry to natural products containing sugars, and other reviews have been written by Rosenthal and Heyns and coworkers. Lindberg and coworkers discussed the combined use of gas-liquid chromatography and mass spectrometry (g.l.c.-m.s.) with reference to alditol acetates and, elsewhere in this Series (see Vol. 29, Chapter 3), Ldnngren and Svensson amplified this topic. The purpose of the present Section is to collate those literature reports relevant to the determination of polysaccharide structures, but not to discuss such matters as the mechanism by which the fragments are formed, information on which can be found in the reviews and articles mentioned. 

The use of alditol acetates for the separation of mixtures of partially methylated sugars not only simplifies the g.l.c. but also the mass spectra, because such compounds contain carbon to carbon bonds of only three types those between (a) carbon atoms that each carries a methoxyl group, or (b) each bears an acetoxyl group, or (c) adjacent carbon atoms having one substituent of each type. Mass spectrometry of partially methylated alditol acetates thus gives rise to relatively few primary fragments that are characteristic of the pattern of substitution. This technique was introduced to carbohydrate chemistry by Lindberg and his associates, and has been employed extensively by them in subsequent structural studies, some of which are discussed next others are listed in Table XXXI (see p. 103). 

Much of our knowledge on the fragmentation patterns of carbohydrate derivatives arises from studies on methylated monosaccharides, but in structural investigations, such compounds are seldom subjected to mass spectrometry. On the other hand, the molecular weight of a permethylated oligosaccharide is significantly less than that of the per(trimethylsilyl) derivative. For this reason, the mass spectra of disaccharides as -their permethylated alditols have been determined by Chizhov and coworkers, Karkkainen, and Krone and Beckey. Trisaccharides have also been studied by Karkkainen, either as permethylated glycosides or as alditols. ... 

The use of mass spectrometry in the structural analysis of carbohydrates, first reported in 1958 (114), was developed in detail by Kochetkov and Chizhov (115). They showed that, under electron impact, the acetylated and methyl ether derivatives of monosaccharides provided a wealth of structural information through analysis of typical fragmentation pathways of the initial molecular ion. This has proved of enormous utility in the structural elucidation of polysaccharides and complex oligosaccharides sequential permethylation, hydrolysis, reduction to the alditol, and acetylation, affords mixtures of peracetylated, partially methylated alditol acetates that can be separated and analyzed by use of a gas chromatograph coupled directly to a mass spectrometer (25). The mass spectra of stereoisomers are normally identical, while the gas chromatographic retention times readily permit differentiation of stereoisomers. 

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