New sialyl LewisX mimic containing an α-substituted β3-amino acid spacer

A highly convergent and efficient synthesis of a new sialyl Lewisx (sLex) mimic, which was predicted by computational studies to fulfil the spacial requirements for a selectin antagonist, has been developed. With a b2,3-amino acid residue L-galactose (bioisostere of the L-fucose moiety present in the natural sLex) and succinate are linked, leading to a mimic of sLex that contains all the required pharmacophores, namely the 3- and 4-hydroxy group of L-fucose, the 4- and 6-hydroxy group of D-galactose and the carboxylic acid of N-acetylneuraminic acid. The key step of the synthesis involves a tandem reaction consisting of a Ndeprotection and a suitable O!N intramolecular acyl migration reaction which is promoted by cerium ammonium nitrate (CAN). Finally, the new sialyl Lewisx mimic was biologically evaluated in a competitive binding assay.