Synthesis of sulfur-containing analogues of alpha GalNAc (Tn-antigen) and beta Gal1,3 alpha GalNAc (T-antigen)

A method for the preparation of thio-analogues of the T- and Tn-antigen was developed. Thus, starting from a known N-acetamido-glucoside derivative, the epidithio analogue of the Tn-antigen was accessible in a four-step reaction sequence. The corresponding epidithio analogue and the thioanhydro derivative of the T-antigen were synthesized starting from a disaccharide derivative. For the preparation of the epidithio analogue the sulfur atoms were introduced via thiocyanates in a stepwise fashion, using mesylate as the leaving group at C-6 and triflate as the leaving group at C-4 in the reducing carbohydrate moiety. The synthesis of the thioanhydro analogue was achieved by introducing a thiocyanate group at C-6 into the glucose moiety, followed by subsequent displacement of a mesylate group at C-4 under inversion of configuration utilizing sodium methoxide.