Synthesis of non-natural glycosylamino acids containing tumor-associated carbohydrate antigens

The synthesis of biologically relevant glycosylamino acids using a non-natural amino acid as the glycosyl acceptor is described. The glycosylation reaction of a monosaccharide tri-chloroacetimidate donor with Fmoc-L-hydroxynorleucine benzyl ester provided the alpha-O-linked product. Conversely, when the glycosylation reaction was carried out with a glycal epoxide donor, the beta-O-linked product predominated. We have used these two complementary glycosylation reactions to synthesize five different glycosylamino acids, each containing the Tn. TF, STn, Lewis(y) or Globo-H tumor-associated carbohydrate antigens. (C) 2003 Elsevier Ltd. All rights reserved.