One‐Pot Glycosylations in the Synthesis of Human Milk Oligosaccharides. Issue 15 (4th April 2014)

• Record Type: Journal Article
• Authors: Arboe Jennum, Camilla; Hauch Fenger, Thomas; Bruun, Linda M.; Madsen, Robert
• Is Part Of: European journal of organic chemistry. Issue 15(2014)
• Page Start: 3232
• Page End: 3241
• Publication Date: 2014-04-04
• Subjects: Carbohydrates -- Oligosac­charides -- Glycosylation -- Thioglycosides; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201400164
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract: 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. Abstract : A one‐pot glycosylation strategy has been developed for assembling the lactosamine–lactose backbone in human milk oligosaccharides, and applied in a concise synthesis of lacto‐ N ‐neofucopentaose I.