An efficient synthesis of a biantennary sialooligosaccharide analog using a 1,6-anhydro-β-lactose derivative as a key synthetic block

An efficient and versatile method for the synthesis of a biantennary octasaccharide derivative was established by combined chemical and enzymatic manipulations of 1,6-anhydro-β-lactose as a key starting material. A key 1,6-anhydro-β-lactose derivative having two unprotected hydroxyl groups at C-3′ and C-6′ positions was prepared and employed for the chemical coupling reaction with a known 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-β-d-glucopyranosyl imidate to afford a tetrasaccharide derivative with two GlcNAc branches in 69% yield. Enzymatic galactosylation using UDP-Gal with a bovine milk β1,4-galactosyltransferase and subsequent sialylation with a recombinant α2,3-sialyltransferase in the presence of CMP-Neu5Ac proceeded smoothly and gave a desired model compound, a bivalent sialooctasaccharide (), in 73% overall yield from the tetrasaccharide intermediate.