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One‐Pot Glycosylations in the Synthesis of Human Milk Oligosaccharides
Author(s) -
Arboe Jennum Camilla,
Hauch Fenger Thomas,
Bruun Linda M.,
Madsen Robert
Publication year - 2014
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201400164
Subject(s) - chemistry , phthalimide , glycosylation , disaccharide , lactose , tetrasaccharide , stereochemistry , total synthesis , moiety , oligosaccharide , fucose , galactose , organic chemistry , biochemistry , polysaccharide
Human milk oligosaccharides contain a well‐defined core structure that makes them interesting synthetic targets for one‐pot glycosylation strategies. In this investigation, a one‐pot procedure was studied in which a galactose thioglycoside is coupled chemoselectively to a phthalimide‐protected glucosamine thioglycoside, and the resulting disaccharide is then coupled to the 3′‐position in lactose. Very high yields of the tetrasaccharide product can be obtained when a protected lactosamine thioglycoside is formed in the first coupling. In contrast, it was not possible to extend the one‐pot process to the synthesis of the corresponding 3″‐linked structures, due to an inefficient synthesis of the lacto‐ N ‐biose thioglycoside in the first glycosylation. This is explained by the reactivity difference between the 3‐ and 4‐positions in phthalimide‐protected glucosamine. The one‐pot procedure has been applied in an efficient synthesis of the pentasaccharide lacto‐ N ‐neofucopentaose I, which is composed of N ‐acetyllactosamine, lactose, and fucose. On the other hand, a stepwise approach was found to be the preferred synthetic pathway for preparation of the isomeric lacto‐ N ‐fucopentaose I, which contains a lacto‐ N ‐biose moiety.