In the organic synthesis of sialoconjugated glycosides, the glycosylation of sialic acid, especially the condensation with a secondary hydroxyl group has been the most difficult reaction. This may be attributable to the facts that a steric hindrance at the anomeric position of sialic acid is increased by a quaternary carbon at its position; 2,3-dehydro form is easy to produce in the condensation reaction by a deoxy at the C-3 position adjacent to the anomeric position; the participation of neighboring groups cannot be utilized in the control of stereochemistry at the anomeric position and a thermodynamically stable configuration is a non-natural .beta.-configuration. Various approaches have been used to solve those problems. An approach is to use the .alpha.-SMe form of sialic. acid as a sialic acid donor, .alpha.-galactose or .alpha.-lactose as a sugar acceptor and dimethyl(methylthio)sulfoniumtriflate as a condensing agent for the glycosylation to synthesize the sialyllactose (.alpha.-form) in a yield of 47% (T. Murase et al, Carbohydr. Res., 188, 71 (1989)). Another approach is to use the .alpha.-SPh form of sialic acid as a sialic acid donor, condensing it with d primary hydroxyl group of the sugar in the presence of PhHgOTf (Tf=trifluoromethanesulfonyl) catalyst to synthesize .alpha.-glycoside in a yield of 24% (E. Kirchner et al, J. Carbohydr. Chem., 7, 453 (1988)). However, many problems still remain in the synthesis of sialoconjugated glycosides, since saccharide chains contained in conjugated glycosides are of high diversity.
USPTO Backgrounds
USPTO Backgrounds