The chemical synthesis of human milk oligosaccharides: Lacto-N-neotetraose (Galβ1→4GlcNAcβ1→3Galβ1→4Glc)

The discovery of innovative methods that offer new capabilities for obtaining individual oligosaccharides from human milk will help to improve understanding their roles and boost practical applications. The total chemical synthesis of lacto-N-neotetraose (LNnT) has been completed using both linear and convergent strategies. The donor and acceptor protecting and leaving group combinations were found to be of paramount significance to successful couplings. [Display omitted] •The total synthesis of lacto-N-neotetraose has been completed using both linear and convergent synthesis approaches.•New synthetic protocols for different glycosidic linkages have been developed and refined.•Aglycone transfer was encountered, and has been solved by tuning the donor-acceptor protecting-leaving group combinations others are within the limit.•New methods for obtaining individual HMO help to improve understanding their roles and boost practical applications.