Anomeric oxazolines

Nucleophile attack becomes a more facile process when the 5-position is activated by an electron-donating group. This strategy has been used extensively in glycoside synthesis, whereby an anomeric oxazoline is used as a glycopyranosyl... 

Other applications of oxazolines have also been discovered. Anomeric oxazolines have now emerged as useful glycosyl acceptors in the glycosylation of sugars. 2-Alkenyloxazolines have been found to undergo asymmetric Michael addition and hetero-Diels-Alder reactions. Further explorations in these areas of oxazoline chemistry will undoubtedly continue and the list of new applications will grow. 

Fused or spiro sugar oxazolines have been synthesized by treating D-fructopyranose or D-fructofuranose 1,2-0-acetonides with nitriles in triflic acid773 (Scheme 5.73). First the activation of the anomeric center takes place with simultaneous isopropy-lidene cleavage to form the oxocarbenium ion intermediate, which is attacked by the nitrile. The resulting nitrilium ion is then trapped by the hydroxyl group in an intramolecular Ritter-like reaction to yield the final product. 

All of the three mentioned mechanisms involve oxocarbenium ion-like transition states and a pair of carboxylic acids at the active site however, they differ in several aspects. The inverting mechanism is a one-step reaction that results in the formation of a product with inverted stereochemistry at the anomeric center. The other two alternatives are retaining in stereochemistry at the anomeric center and differ from each other primarily in the nature of the intermediate in the second mechanism, this species is a covalent enzyme adduct, whereas in the third case it is believed to be a bicyclic oxazoline or oxazolinium ion. ... 

Fig. 8. Alternative catalytic nucleophiles, (a) Tyrosine functions as the catalytic nucleophile in Clan GH-E sialidases and trans-silalidases, with the assistance of a proximal carboxylate amino acid side chain, (b) Anchimeric assistance in hexosaminidases involving reaction of the A -acetyl group of the substrate with the anomeric carbon to form an oxazoline intermediate in the enzyme active site, (c) Sugar thiazolines are noncleavable S-linked inhibitors of hexosaminidases that use an oxazoline intermediate. Enz5mie selectivity can be further tuned by varying i . ...

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