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Complex Structures of Antennary Human Milk Oligosaccharides − Synthesis of a Branched Octasaccharide
Author(s) -
Knuhr Petra,
CastroPalomino Julio,
Grathwohl Matthias,
Schmidt Richard R.
Publication year - 2001
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 - 10.1002/1099-0690(200111)2001:22<4239::aid-ejoc4239>3.0.co;2-m
Subject(s) - tetrasaccharide , chemistry , retrosynthetic analysis , disaccharide , oligosaccharide , stereochemistry , glycosylation , trisaccharide , glycoside , ketose , cleavage (geology) , protecting group , total synthesis , aldose , organic chemistry , biochemistry , polysaccharide , alkyl , geotechnical engineering , fracture (geology) , engineering
We have developed a highly convergent synthetic route for the synthesis of the branched structure of human milk octasaccharide β‐ D ‐galactopyranosyl‐(1→3)‐2‐acetamido‐2‐de oxy‐β‐ D ‐glucopyranosyl‐(1→3)‐β‐ D ‐galactopyranosyl)‐(1→4)‐2‐acetamido‐2‐deoxy‐β‐ D ‐glucopyranosyl‐(1→6)‐[β‐ D ‐galactopyranosyl‐(1→3)‐2‐acetamido‐2‐deoxy‐β‐ D ‐glucopyranosyl‐(1→3)]‐β‐ D ‐galactopyranosyl‐(1→4)‐α,β‐ D glucopyranose ( 1 ). In the retrosynthetic analysis, target structure 1 was disconnected into building blocks 2−6 . Starting from only four known building blocks − 4 , 7 , 8 , and 12 − the required three disaccharide units were obtained, resulting after further protecting group manipulation and glycoside bond formation in the desired tetrasaccharides 13 and 16 . Cleavage of the TBDMS group of 13 afforded tetrasaccharide 14 , which was transformed into isolactosamine‐β‐(1→3)‐lactosamine trichloroacetimidate 15 . Removal of the 4b,6b‐ O ‐benzylidene group of tetrasaccharide 16 gave the lacto‐ N ‐tetraose acceptor 17 , to afford the protected octasaccharide 18 on glycosylation with donor 15 . Complete deprotection of the octasaccharide by way of 19 afforded target human milk oligosaccharide 1 in a short and efficient route.