Carbohydrates, stereochemical effects

J. M. Sugihara and W. J. Teerlink, Stereochemical effects in the nucleophilic displacement reactions of primary carbohydrate benzene sulfonate esters with sodium iodide, J. Org. Chem. 29 550 (1964). 

Surprisingly, the introduction of the pyridine ring not only influences the velocity of the enzymatic transformations, but also induces promising stereochemical effects (Table 1). For instance, at 40% conversion (R)-phenylethanol is obtained from the pyridyl acetate 25 with 73 % ee, whereas the value for the corresponding phenylacetate is only 28%. Also, the secondary alcohol liberated from the ester 26 displays 98% ee at 40% conversion, whereas the respective phenylacetate leads to 1-phenylpropanol with 94% ee but at a conversion rate of 12% only [19,20]. These results demonstrate that the stereoselecting properties of penicillin acylase may be enhanced by appropriate engineering of the substrate. This is of particular interest since this enzyme has already been used for the kinetic resolution of various chiral alcohols [21-24], e.g. furyl alkyl carbinols [24], which are valuable precursors for the de novo synthesis, with moderate to high ee values, of carbohydrates. 

From this preliminary review of monosaccharide glycosides, it is possible to see that the fragmentation pattern in FAB mass spectra is governed by at least three factors whose importance may vary (1) nature of the aglycone, (2) configuration of the anomeric carbon (3) remote stereochemical effects (i.e., the relative stereochemistry of the other carbohydrate carbons). 

The amount of information available on stereochemical effects in mass spectrometry is very large. Compiling this article, however, highlighted the need for more thorough studies on given families of oxygen heterocycles. The few scattered data published to date warrant this closer examination. Carbohydrates seem to be the exception to this statement, due largely to their broad use in various applications. 

Remote Stereochemical Effect. The stereochemistry of the various chiral centers in a given carbohydrate ring may affect the spectra. This is mainly the result of the degree of binding that can be accomplished and the number of... 

A study has been carried out on the radicals derived by lead tetra-acetate treatment of ulose oximes, e.g., (6). The signals were intense and persistent and can be used to study stereochemical effects relating to the carbohydrate rings and also the oxime groups themselves. ... 

Reports of conformational control in the mass spectra of alkylated 2- and 5-methylcyclohexane-l,3-diols are of interest to carbohydrate chemists-for example, the configuration of the C-methyl group leads to secondary stereochemical effects in eliminations specific for the cis- and /m w-dioIs. ... 

The characteristics of enzymes are their catalytic efficiency and their specificity. Enzymes increase the reaction velocities by factors of at least one million compared to the uncatalyzed reaction. Enzymes are highly specific, and consequendy a vast number exist. An enzyme usually catalyzes only one reaction involving only certain substrates. For instance, most enzymes acting on carbohydrates are so specific that even the slightest change in the stereochemical configuration is sufficient to make the enzyme incompatible and unable to effect hydrolysis. 

The stereochemical outcome for addition of r-l,3-dioxolan-4-yl and oxiranyl radicals to phenyl vinyl sulfone has been probed. The results indicated that the symanti selectivity could be altered by changing the group next to the radical in the diox-olanyl case but not in the oxiranyl case (bulky groups had a large xyn-directing effect) (Scheme 39). Several alkenyl-lactones and -lactams have been subjected to hydrosilylation conditions using carbohydrate-derived thiols as homochiral polarity reversal catalysts (yields 25-96% ee 5-95%) " ... 

Substances such as carbohydrates, amino acids, and other small molecules available from natural sources are valuable starting materials for the synthesis of stereochemi-cally defined substances. Suggest a sequence of reactions which could effect the following transformations, taking particular care to ensure that the product would be obtained stereochemically pure. 

J. K. N. Jones and his colleagues have extensively studied the reaction of sulfuryl chloride with carbohydrates.21-29 This work has elucidated the stereochemical principles involved in the various transformations, and has made available a convenient and effective procedure for the preparation of chlorodeoxy sugars. Several examples of the utility of such derivatives, obtained by way of a reaction with sulfuryl chloride, in the synthesis of other rare sugars are discussed in Section III (see p. 281). In the present Section, the studies on the reaction itself are surveyed. 

Application of mass spectrometry to stereochemical analysis in the monosaccharide series is limited by the lack of experimental studies, by the absence of a generalizing, theoretical concept based upon modem conformational analysis, and by lack of precise knowledge of the mechanism and stereochemistry of the reactions taking place in the mass spectrometer. The only investigation in which a thorough study has been made of the effect of the stereochemical features of carbohydrates upon their mass spectra is that of Heyns and Scharmann, who measured the mass spectra of a number of permcthylated methyl pentopyranosides, namely, methyl tri-0-methyl-j8-D-ribo-(13), -arabino-(14), -xylo-(lS), and -lyxo-pyrano-sides (16), and of methyl tri-Omethyl-a-D-lyxopyranoside (17). 

A. S. Shashkov, G. M. Lipkind, Y. A. Knirel, and N. K. Kochetkov, Stereochemical factors determining the effects of glycosylation on the 13C chemical shifts in carbohydrates, Magn. Reson. Chem., 26 (1988) 735-747. 

The conclusions reached by Isbell8 and other workers3-4 5 thus rendered clear the possible influence of neighboring-group participation on the stereochemical path of reaction. But the really profound effect that neighboring-group participation may have on the rate of reaction was not recognized in carbohydrate chemistry until after the discovery of this phenomenon by Winstein and coworkers. For example, a study by these... 

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