Synthesis of alpha-lactosyl-(1-->3)-L-glycero-alpha-D-manno-heptopyranoside, a partial oligosaccharide structure expressed within the lipooligosaccharide produced by Neisseria gonorrhoeae strain 15253.

The glycosyl donor, hepta-O-benzyl-beta-lactosyl trichloroacetimidate (4) was prepared by treating hepta-O-benzyl-lactose with trichloroacetonitrile in the presence of potassium carbonate. The acceptor, methyl 2-O-benzyl-4,6-O-benzylidene-7,8-dideoxy-alpha-D-manno-oct-7-enopyranoside (8) was synthesized by hydrolysis of a 3,4-butane diacetal of methyl L-glycero-alpha-D-manno-oct-enopyranoside and subsequent benzylidenation. Glycosidation of the donor 4 with the acceptor 8 in 1,4-dioxane using Me(3)SiOTf as a promoter for 1 h at room temperature gave methyl (2,3,4,6-tetra-O-benzyl-beta-D-galactopyranosyl)-(1-->4)-(2,3,6-tri-O-benzyl-alpha-D-glucopyranosyl)-(1-->3)-2-O-benzyl-4,6-O-benzylidene-7,8-dideoxy-alpha-D-manno-oct-7-enopyranoside (9) as a major product (59%). The oct-enopyranoside moiety of the trisaccharide 9 was converted to a heptopyranoside (80%) by oxidative cleavage with OsO(4)-NaIO(4) and subsequent reduction. Hydrogenolysis of the resulting trisaccharide and subsequent acetylation gave the peracetate of alpha-lactosyl-(1-->3)-Hep. Deacetylation of the peracetate afforded the title trisaccharide.