A Structural-Reporter Group to Determine the Core Conformation of Sialyl Lewis x Mimetics.

The d-Glc N Ac moiety in sialyl Lewis x (sLe x , 1 ) acts predominantly as a linker to position the d-Gal and the l-Fuc moieties in the bioactive spatial orientation. The hypothesis has been made that the NHAc group of Glc N Ac pushes the fucose underneath the galactose and, thus, contributes to the stabilization of the bioactive conformation of the core of sLe x ( 1 ). To test this hypothesis, Glc N Ac mimetics consisting of ( R , R )-1,2-cyclohexanediols substituted with alkyl and aryl substituents adjacent to the linking position of the fucose moiety were synthesized. To explore a broad range of extended and spatially demanding R-groups, an enzymatic approach for the synthesis of 3-alkyl/aryl-1,2-cyclohexanediols ( 3b-n ) was applied. These cyclohexanediol derivatives were incorporated into the sLe x mimetics 2b-n . For analyzing the relationship of affinity and core conformation, a 1 H NMR structural-reporter-group concept was applied. Thus, the chemical shift of H-C5 Fuc proved to be a sensitive indicator for the degree of pre-organization of the core of this class of sLe x mimetics and therefore could be used to quantify the contribution of the R-groups.