The Total Chemical Synthesis of Tumor-Associated Forssman Antigen

Forssman antigen is a common heterophile antigen which is a glycosphingolipid with the alphaGalNAc(1→3)betaGalNAc(1→3)alphaGal(1→3)alphaGal(1→4)betaGlcl→Ceramide sequence. Studies by immunohistochemical staining method using both monoclonal and polyclonal antibodies have confirmed that this antigen is absent from normal human tissues. However, Forssman antigen is found in several forms of human cancer, including gastric, colon, and lung cancers, making it a tumor-specific antigen. Consequently, the development of an immune response against the carbohydrate portion of Forssman antigen could be highly valuable for cancer immunotherapy. The present thesis describes an investigation toward the total chemical synthesis of Forssman antigen for potential immunological studies.;The target pentasaccharide was prepared from commercially available mono- and disaccharides. Two approaches to assemble the pentasaccharide have been explored using either an iterative 2+1+1+1 or a more converging 3+2 strategy. In the meantime, an efficient and practical chemical conversion of N-acetyl-D-glucosamine to N-acetyl-D-galactosamine has been developed.