Why are the hydroxy groups of partially protected N-acetylglucosamine derivatives such poor glycosyl acceptors, and what can be done about it? A comparative study of the reactivity of N-acetyl-, N-phthalimido-, and 2-azido-2-deoxy-glucosamine derivatives in glycosylation. 2-Picolinyl ethers as reactivity-enhancing replacements for benzyl ethers.
Competition experiments were used to determine that the 4-OH of a 2-deoxy-2-azidoglucose derivative is more reactive than that of the corresponding N-phthalimido glucose derivative which, in turn, is more easily glycosylated than the N-acetyl derivative. Glycosylation of the 4-OH groups of the N,N-diacetyl and N-acetyl-N-benzyl glucosamine was also found to be superior to that of the simple N-acetyl substance. The 3-O-picolinyl ether of a 4,6-O-benzylidene-protected N-acetylglucosamine was shown to have a strong intramolecular hydrogen bond to the adjacent acetamide group. This interaction does not persist in the 3-O-picolinyl-6-O-benzyl N-acetylglucosamine derivative, owing to a probable competing hydrogen bond between the 4-OH and the picolinyl ether. However, in the 3-O-picolinyl-4-O-benzyl N-acetylglucosamine regioisomer the picolinyl-acetamide hydrogen bond persists and leads to an enhancement of reactivity of the 6-OH, over and above that in the corresponding 3-O-benzyl ether, due to disruption of the typical intermolecular amide hydrogen bonding scheme. It is demonstrated that the picolinyl ether is readily removed by hydrogenolysis at atmospheric pressure and room temperature.
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Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois 60607-7061, USA.
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D000117:Acetylglucosamine / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism*; D001386:Azides / Q000737:chemistry* / Q000378:metabolism; D001593:Benzyl Compounds / Q000737:chemistry* / Q000378:metabolism; D001667:Binding, Competitive; D004988:Ethers, Cyclic / Q000737:chemistry* / Q000378:metabolism; D006031:Glycosylation; D008738:Methyl Ethers / Q000737:chemistry* / Q000378:metabolism; D010797:Phthalimides / Q000737:chemistry* / Q000378:metabolism; D010847:Picolines / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
D001386:Azides; D001593:Benzyl Compounds; D004988:Ethers, Cyclic; D008738:Methyl Ethers; D010797:Phthalimides; D010847:Picolines; D000117:Acetylglucosamine