Introduction into carbohydrates

Of particular significance to the methodology of fluorine introduction into carbohydrate molecules by nucleophilic substitution is the work of Morishima [61 ]. As depicted in Table 7, the DAST route (entries 6,7 and 8) gave AS [4,rO] and MS[4,rO] exclusively, whereas the triflate/TASF tandem allowed 8 2 together withAS[4,rO] (entry 5) orE[4,H-3] (entry 9). 

For mixture.s the picture is different. Unless the mixture is to be examined by MS/MS methods, usually it will be necessary to separate it into its individual components. This separation is most often done by gas or liquid chromatography. In the latter, small quantities of emerging mixture components dissolved in elution solvent would be laborious to deal with if each component had to be first isolated by evaporation of solvent before its introduction into the mass spectrometer. In such circumstances, the direct introduction, removal of solvent, and ionization provided by electrospray is a boon and puts LC/MS on a level with GC/MS for mixture analysis. Further, GC is normally concerned with volatile, relatively low-molecular-weight compounds and is of little or no use for the many polar, water soluble, high-molecular-mass substances such as the peptides, proteins, carbohydrates, nucleotides, and similar substances found in biological systems. LC/MS with an electrospray interface is frequently used in biochemical research and medical analysis. 

From among the variety of non-carbohydrate precursors, acetylenes and alkenes have found wide application as substrates for the synthesis of monosaccharides. Although introduction of more than three chiral centers having the desired, relative stereochemistry into acyclic compounds containing multiple bonds is usually difficult, the availability of such compounds, as well as the choice of methods accessible for their functionalization, make them convenient starting-substances for the synthesis. In this Section is given an outline of all of the synthetic methods that have been utilized for the conversion of acetylenic and olefinic precursors into carbohydrates. Only reactions leading from dialkenes to hexitols are omitted, as they have already been described in this Series.7... 

The subject of relative reactivities of hydroxyl groups in carbohydrates has been discussed previously in this Series.1,2 In these articles, emphasis was placed on the selective introduction of substituents into carbohydrates. A much less exploited approach for the preparation of partially substituted carbohydrates involves the selective removal of hydroxyl-protecting groups from carbohydrate derivatives. The purpose of the present article is to draw attention to this relatively neglected aspect of synthesis in the belief that the greater use of de-... 

Since the pioneering work of Karl Freudenberg on displacements of carbohydrate p-toluene-sulfonates [1-5], bimolecular nucleophilic substitutions became one of the most employed and useful reactions in carbohydrate chemistry. Indeed SN2-type reactions have allowed the introduction of a variety of heteroatoms (halogens, N-, O-, S-) into carbohydrates, and the resulting compounds have been used in many synthetic and biological contexts [6],... 

G. S. Bethell and R. J. Ferrier, The relayed introduction of alkylthio-groups into carbohydrates derivatives A novel synthesis of amicetose, J. Chem. Soc. Perkin / (1993) 1400-1405. 

Akiyama, Y., Hiramatsu, C., Fukuhara, T., and Kara, S. 2006. Selective introduction of a fluorine atom into carbohydrates and a nucleoside by ring-opening fluorination reaction of epoxides. Journal of Fluorine Chemistry, 127 920-23. 

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. 

As for the introduction of a selenium atom into carbohydrates, addition reactions to glycals are also effective. Thus, the glucal 81 can be treated with phenylselenyl chloride and gives mainly the fraws-diaxial product 153 (O Scheme 69) [112]. Similarly, azidophenylselenylation of perbenzylated glucal 104 proceeds smoothly to give 2-5 e-phenyl-2-selenoglycosylazides 154 and 155 (O Scheme 69) [113]. 

Epoxide ring opening is also an alternative route for the introduction of a phosphorus atom into carbohydrates. Thus, the U-allo epoxide 72 reacts with LiPPh2, giving an intermediate phosphine which is spontaneously oxidized to the 2-phosphonate 187 [125], whereas the isomeric D-manno epoxide 188 affords the regioisomeric 3-phosphonate 189 (O Scheme 80) [124]. 

Reviewed was the use of our newly developed Pd-catalyzed glycosylation reaction for the incorporation of rare and unnatural sugars on unique biologically relevant structures. This de novo approach for the introduction of carbohydrate structures, under non-Lewis acidic conditions, into preexisting structural motifs is unique. To date, there simply does not exist an equivalent chemical or biochemical method for the stereoselective glycosylation of under-fimctionalized D- and L-sugars, which can be elaborated into a myriad of carbohydrate analogues. Not to mention this method also allows for complete a/(3-stereocontrol. The power and uniqueness of this approach is probably best... 

The regio selectivity observed in the acylation of underivatized pyranoses in principle parallels that recorded for the classical chemical introduction of acyl groups into carbohydrates. However, if the 6-OH groups are protected first or deoxygenated, in the corresponding enzymatic reactions selectivities are observed which can not be realized with classical chemical methods. By careful choice of solvent and lipase, it is possible to rnodifiy selectively a number of C6 protected pyranoses at the secondary hydroxy groups (Table 18-2). 

Glycosylation, the introduction of carbohydrate moieties into peptides and proteins. Glycosylation is the most complex post-translational modification of proteins [H. Schachtner, Curr. Opin. Struct. Biol. 1991, 1, 755 C. Abeijon, C. B. Hirschberg, Trends Biochem. Sci. 1992, 17, 32]. 

The biochemical rationale for the introduction of fluorine into carbohydrates is presented and exemplified by a review of transport, metabolic and enzymatic studies with deoxyfluorosugars. Recent biochemical results with 3-deoxy-3-fluoro-D-glucose (3FG) and 4-deoxy-4-fluoro-D-glucose (4FG) illustrate the reactivity of the C-F bond. Thus unlike 3FG, when 4FG is incubated with Pseudomonas putida extensive fluoride ion release occurs due to the presence of an outer membrane protein. Using D-[6- H]-4FG and D-[U-... 

The rationale for the introduction of fluorine into carbohydrates has been extensively cited (i). Initially, the idea was based on the close similarity in size and electronegativity between fluorine and a hydroxyl group when attached to carbon (2). Support for this contention was provided by a comparative X-ray crystallographic... 

The natural occurrence of the C-F bond in carbohydrates is restricted to nucleocidin, an antibiotic in which the hydrogen at C-4 of this ribofuranoside is replaced by fluorine. In contrast, during the last 10 years, new synthetic methods for the introduction of both and F into carbohydrates have led to an explosive growth in the number and variety of fluorinated sugars. Therefore, compounds that were relatively rare have become readily accessible for chemical and biochemical research. 

The introduction of an amino-group into carbohydrates has been achieved by displacement of a tosyloxy or similar leaving group by participation of a neighbouring 0-carbamoyl group (—CONHR). Thus, 2-amino-l,6-anhydro-2-deoxy-j3-D-mannose was prepared from 1,6 3,4-dianhydro-2-0-tosyl- 8-D-glucopyranose as outlined in Scheme 1. A similar reaction has been proposed by Barton and Motherwell/ ... 

The introduction of electronic asymmetry into this class of bis(diaryl)phosphinites has been used to design catalysts that can afford both enantiomers of naproxen nitrile. If the carbohydrate scaffold is based on methyl o-D-fructol uranosidc (29), (i )-naproxen nitrile is produced. In a similar manner to the results above, electron-donating aryl substituents on phosphorus afford... 

In carbohydrate chemistry, the most described method for the preparation of saccharidic thionocarbamates involves preliminary introduction of the amine function on a partially or non-protected saccharidic template. The condensation of amino sugars with carbon disulfide or thiophosgene leads to cyclization in 1,3-oxazolidine- or l,3-oxazine-2-thiones. This reaction involves the formation of an intermediate isothiocyanate, which reacts further with a 3- or y-located hydroxyl group. The viability and facility of this process depends on the saccharidic ring size and the inherent strain. Some major rules can be put into light from the cases studied 30... 

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