The Tn (GalNAcα1→O-Ser/Thr) epitope is a major tumor-associated O-linked glycopeptide motive of cell surface glycoproteins, which are expressed in over 70% of human epithelial cancers such as lung, colon, stomach and breast carcinomas. In normal cells, however, the Tn antigen is cryptic, where it is further glycosylated giving rise to complex carbohydrates of the mucin-type glycoproteins. This antigen has also been identified as a partial structure of the HIV envelope glycoprotein gp120.1
Herein we report mild Pd-catalyzed method for the stereoselective synthesis of C-linked Tn-antigen, which represent stable nonhydrolyzable epitop. The synthesis starts from commercial available methyl ester 1, which was transformed to bromide derivative 2 through reduction and followed Wittig reaction with (bromomethyl)triphenylphosphonium bromide. The key step was Suzuki coupling of galactal boronate 3 with prepared bromide 2 provided enol ether 4. The final C-analog of Tn-antigen 5 was observed after several transformation steps.
Acknowledgement: This work was supported by the Grant Agency of the Czech Republic (grant No. P207/12/P713).
References
[1.] D. Urban, T. Skrydstrup, J.-M. Beau: Chem. Commun., 1998, 955.
