Reactions at the anomeric center of sugars are of immense importance in virtually all areas of chemistry-organic, biological theoretical, physical, and medicinal. For example, it is increasingly apparent that an glycoproteins the """"""""glyco"""""""" may be more important that the """"""""protein"""""""" and the """"""""glyco"""""""" is full of anomeric centers. Oligosaccharides are now known to be important immunodeterminants. Glycolytic enzymes work on anomeric centers. Therefore, not surprisingly, chemists have invested enormous effort in synthetic, theoretical, and physical studies of the anomeric center, and its importance has been enshrined in concepts such as the anomeric effect and stereoelectronic control. Nevertheless, the more the phenomenon is studied, the more gaps and shortcomings are revealed. We have recently discovered a reaction which promises to accommodate a broad spectrum of investigations dealing with the anomeric center. The process in question occurs chemospecifically when n-pentenyl glycosides are treated with halonium ions. Among the reactions occurring are (1) hydrolysis of the glycoside under neutral conditions, (2) specific deprotection of the anomeric center in the presence of other protecting groups, specific activation for (3) glycoside exchange or (4) oligosaccharide couplings, and (5) arming or disarming the glycosidic group by changing the C2 substituent from an ester to an ether. Each of the first four attributes has precedent. However, the n-pentenyl glycoside is the only sugar derivative that incorporates all four. Even more important is the unique, overriding, and unprecedented attribute (5). Particular appeal arises from the simplicity of the technique. The group is easy to install by using a commercially available reagent, and utilizes classical methods. Being an O-alkyl glycoside, it is sturdy, stable, and inherits the enormous body of """"""""know-how"""""""" on handling this class of compounds. The advantages for oligosaccharide synthesis are obvious, and because the oxidative process is neutral, it is particularly advantageous for dealing with sensitive molecules. From the standpoint of mechanism, the postulated intermediate carries an oxonium ion at the anomeric center similar to that postulated for protonated glycosides. Therefore, oxidative deglycosidation can be used as a model for studying enzymatic glycolytic cleavage, the neutral oxidative conditions being more appealing than the acid catalyzed models traditionally employed. Concepts of stereoelectronic control can also be tested under neutral conditions.
|Schofield, L; McConville, M J; Hansen, D et al. (1999) CD1d-restricted immunoglobulin G formation to GPI-anchored antigens mediated by NKT cells. Science 283:225-9|
|Debenham, J S; Debenham, S D; Fraser-Reid, B (1996) N-Tetrachlorophthaloyl (TCP) for ready protection/deprotection of amino sugar glycosides. Bioorg Med Chem 4:1909-18|