Sugars trimethylsilylation

Trichloroacetonitrile reacts with glycosidic hydroxy groups of protected sugars to form glycosyl trichloroacetimidates (R. R. Schmidt, 1980, 1984,1985,1986 B. Wegmann, 1988). The imidate is substituted by alcohols in the presence of trimethylsilyl trifluoromethanesulfonate... 

Etherification. The reaction of alkyl haUdes with sugar polyols in the presence of aqueous alkaline reagents generally results in partial etherification. Thus, a tetraaHyl ether is formed on reaction of D-mannitol with aHyl bromide in the presence of 20% sodium hydroxide at 75°C (124). Treatment of this partial ether with metallic sodium to form an alcoholate, followed by reaction with additional aHyl bromide, leads to hexaaHyl D-mannitol (125). Complete methylation of D-mannitol occurs, however, by the action of dimethyl sulfate and sodium hydroxide (126). A mixture of tetra- and pentabutyloxymethyl ethers of D-mannitol results from the action of butyl chloromethyl ether (127). Completely substituted trimethylsilyl derivatives of polyols, distillable in vacuo, are prepared by interaction with trim ethyl chi oro s il an e in the presence of pyridine (128). Hexavinylmannitol is obtained from D-mannitol and acetylene at 25.31 MPa (250 atm) and 160°C (129). 

Polarimetric analysis of sorbitol and mannitol in the presence of each other and of sugars is possible because of their enhanced optical rotation when molybdate complexes are formed and the higher rotation of the mannitol molybdate complex under conditions of low acidity (194). The concentration of a pure solution of sorbitol may be determined by means of the refractometer (195). Mass spectra of trimethylsilyl ethers of sugar alcohols provide unambiguous identification of tetritols, pentitols, and hexitols and permit determination of molecular weight (196). 

The 4,6-O-benzylidene group is also cleaved under these conditions, but the anomeric linkage between sugars is not affected. Anomeric trimethylsilyl-... 

The mono-silylated or free acetamides, which are liberated during silylation with 22 a, can, furthermore, interfere with any subsequent reaction, e.g. with electrophiles. Thus in the one-pot/one-step silylation, Friedel-Crafts catalyzed, nucleoside synthesis starting from protected sugar derivatives and pyrimidine or purine bases, the mono- or bis-silylated amides such as 22 a can compete with less reactive silylated heterocycHc bases for the intermediate electrophilic sugar cation to form protected 1-acetylamino sugars in up to 49% yield [42, 47]. On silylation with trimethylsilylated urea 23 a the Hberated free urea is nearly insoluble in most solvents, for example CH2CI2, and thus rapidly precipitated [43]. 

Because activated 4-0-trimethylsilylated-2, 3, 5 -0-acyluridines such as 3 are also obtained as reactive intermediates in the Friedel-Crafts-catalyzed silyl-Hilbert-Johnson reaction [59, 59 a] of persilylated uracils or 6-azauracils such as 227 with sugars such as l-0-acetyl-2,3,5-tri-0-benzoyl-/9-D-ribofuranose 228 in the presence of SnCl4, treatment of the reactive intermediate 229 with a large excess of pyrrolidine neutralizes the SnCLi. used and aminates 229 to afford the protected 6-aza-cytidine 230, although in 57% yield only [49, 59] (Scheme 4.20). 

Different kinds of nucleosides (778) were prepared by condensation of compound 400 (see Section 11,3) with trimethylsilylated uracils under Lewis acid catalysis, and removal of one fluorine atom at C-2 of the sugars. Uridine 5 -(2-acetamido-2,4-dideoxy-4-fluoro-a-D-galactopyranosyl di-... 

Mateo, R., Bosch, G., Pastor, A., and Jimenez, M. (1987). Capillary column gas chromatographic identification of sugars in honey as trimethylsilyl derivatives. /. Chromatogr. A 410, 319-328. 

Because of the high stability of the triphenylmethyl carbocation, the reductive ether cleavage of trityl ethers with EtySiH/trimethylsilyl triflate (TMSOTf) is highly successful. This reaction even occurs in the presence of highly reactive sugar ketals, leaving the ketals intact (Eq. 126).269... 

ADAMS, M.A., CHEN, Z., LANDMAN, P., COLMER, T., Simultaneous determination by capillary gas chromatography of organic acids, sugars, and sugar alcohols in plant tissue extracts as their trimethylsilyl derivatives, Anal. Biochem., 1999, 266, 77-84. 

Davison, P. K., Young, R. (1964). Gas chromatography of carbohydrates the quantitative determination ofthe free sugars of plants as their trimethylsilyl ethers. Journal of Chromatography A, 41, 12-21. 

Conversion of sugars into their O-trimethylsilyl (Me3Si) derivatives is most commonly achieved by reaction in pyridine with hexamethyl-disilazane (1) and chlorotrimethylsilane (2) according to equation (I). 

In a typical procedure, 10 mg of a sugar is dissolved in 1 ml of pyridine, treated successively with 0.2 ml of hexamethyldisilazane and 0.1 ml of chlorotrimethylsilane, and the mixture shaken for a few seconds. Reaction is normally complete within 5 minutes. This treatment corresponds to the original procedure used by Sweeley and colleagues,5 and is the method used in the great majority of cases. Apart from the deliberate use of other trimethylsilylating reagents, most of the variations on this fundamental reaction have been designed to meet certain special conditions. 

With simple compounds, the trimethylsilylation reaction is rapid, but, if the reaction proceeds slowly, short reaction-times lead to incomplete substitution this is generally manifest on the gas chromatogram because of the presence of an unexpectedly large number of peaks.117 Maltose has been reported to require reaction for at least 30 minutes,118 and the time needed for complete trimethylsilylation of amino sugars has been examined by Oates and Schrager.36... 

In a study using 14C-labelled sugars, it was shown that the recovery of trimethylsilyl derivatives was approximately 25%, whereas only... 

Despite the many advantages of converting free sugars into their O-trimethylsilyl derivatives, the formation of anomeric and isomeric derivatives (see Section IV, p. 38) may constitute a problem, especially with complex mixtures. Much effort has, therefore, been expended in seeking carbohydrate derivatives, suitable for analysis, in which the anomeric center has been eliminated. This may conveniently be accomplished by oxidation to the acid or lactone, by... 

The recovery of trimethylsilyl and trifluoroacetyl derivatives has been examined by use of 14C-labelled sugars, and it has been shown that glucose trifluoroacetate is recovered208 to the extent of 3 to 5% on SF-96, or of 5 to 14% on Carbowax 20 M. 

Wood and Siddiqui233 similarly prepared butaneboronates of sugars, and these were then trimethylsilylated in the usual way. 

Although many analyses are performed on alditol acetates (see Section VII, p. 56), in order to avoid the formation of multiple peaks, such a reduction is not practical when the mixture contains ketoses, notably fructose. Such analyses are mainly encountered with medical samples and in the examination of sugars occurring free in Nature. Furthermore, the peak-area ratios may be used as a means of identification, to check on the completeness of trimethylsilylation,67,89 and, despite the complex chromatograms obtained from trimethyl-silyl derivatives, they have the merit of being rapidly formed.89 For all of these reasons, improvements in the separation of monosaccharides as their trimethylsilyl derivatives continue to be of considerable importance. 

Mason and Slover187 studied the separation of monosaccharides as the O-trimethylsilyl derivatives of the oximes, as an alternative method to analyzing for sugars in foods, and Clayton and H.G. Jones188 used trimethylsilylated D-glucose oxime. Both groups of workers referred to the instability of these derivatives, as noted in Section III (see p. 23). Laine and Sweeley189 proposed a similar method that used the methoxime derivatives. 

Preliminary work has shown that sugars may be separated directly as their butaneboronates,232 or after subsequent trimethylsilylation.233 In the former procedure, a column of 3% of OV-17 was used at 200°, and, in the latter, a column of 3% of ECNSS-M was programmed from 100° at 2° per minute. 

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