Complex structures of antennary human milk oligosaccharides - Synthesis ofa branched octasaccharide

We have developed a highly convergent synthetic route for the synthesis of the branched structure of human milk octasaccharide beta -D-galactopyranosy l-(1 -->3)-2-acetamido-2-deoxy-beta -D-glucopyranosyl-(1 -->3)-beta -D-gala ctopyranosyl)-(1 -->4)-2-acetamido-2-deoxy-beta -D-glucopyranosyl-(1 -->6)- [beta -D-galactopyranosyl-(1 -->3) -2-acetamido-2-deoxy-beta -D-glucopyrano syl-(1 -->3)]-beta -D-galactopyranosyl-(1 -->4)-alpha,beta -D-glucopyranose (1) . In the retrosynthetic analysis, target structure I 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, resul ting after further protecting group manipulation and glycoside bond formati on in the desired tetrasaccharides 13 and 16, Cleavage of the TBDMS group o f 13 afforded tetrasaccharide 14, which was transformed into isolactosamine -beta-(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 1 5. Complete deprotection of the octasaccharide by way of 19 afforded target human milk oligosaccharide 1 in a short and efficient route.