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

Abstract

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 α- O-linked product. Conversely, when the glycosylation reaction was carried out with a glycal epoxide donor, the β- 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.