Oxazolines disaccharide synthesis

Compound 6-Pre closely resembles the intermediates used by Kusumoto jet al. ([this volume) and by van Boeckel et al. (16) for the preparation of disaccharide oxazolines, which were then elaborated into fully phosphorylated analogs (1,4 -diphosphates). In a formal sense, therefore, the synthesis of 6-Pw effectively constitutes a synthesis, by our revised route, or the 1,4 -bisphosphate having palmitoyl groups at positions 2, 3, 2, and 6. An additional palmitoyl group could be attached at position 4 if desired. 

Although the oxazoline method is a general procedure for the synthesis of 8-glycosides, the acylamido groups at C-2 of the starting materials are unchangeable to others. We next examined a more flexible method by which a variety of fatty acyl residues can be introduced after the formation of disaccharides (Figures 10 and 11). 

Figure 9. Synthesis of di-N-acyl disaccharide derivatives via the oxazoline route.

It is known that the hydrolysis reaction proceeds via an oxazolinium ion intermediate. Based on this Kobayashi and coworkers succeeded in designing a disaccharide oxazoline transition state analog self-condensing substrate to revert the native action of HAase towards synthesis of hyaluronan and derivatives thereof (see Figure 9.15). 

AT-Acyl Derivatives. — O-Protected 2-deoxy-2-trichloroacetamido-D-glucopyranosyl trichloroacetimidates, e.g. 54, have been used in the synthesis of -linked disaccharides with some success (see Chapter 3). The products could be converted into the corresponding 2-acetamido-derivatives by radical dechlorination (BuaSnH, AIBN). The 2-trichIoromethyl-oxazoline derivative 55, formed from 3,4,6-tri-0-acetyl-2-deoxy-2-trichloroacetamido-D-glucosyI acetate (on reaction... 

Syntheses of the oxazoline (139), a useful intermediate in the preparation of /3-glycosides from 2-acetamido-2-deoxy-D-glucopyranose, and the disaccharide oxazoline (140), a compound that may prove to be useful in the synthesis of several oligosaccharides found in human milk and the blood-group substances, have been described. 

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