| Summary: | The <span style="font-variant: small-caps;">d</span>-Glc<i>N</i>Ac moiety in sialyl Lewis<sup>x</sup> (sLe<sup>x</sup>, <b>1</b>) acts predominantly as a linker to position the <span style="font-variant: small-caps;">d</span>-Gal and the <span style="font-variant: small-caps;">l</span>-Fuc moieties in the bioactive spatial orientation. The hypothesis has been made that the NHAc group of Glc<i>N</i>Ac pushes the fucose underneath the galactose and, thus, contributes to the stabilization of the bioactive conformation of the core of sLe<sup>x</sup> (<b>1</b>). To test this hypothesis, Glc<i>N</i>Ac mimetics consisting of (<i>R</i>,<i>R</i>)-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 (<b>3b-n</b>) was applied. These cyclohexanediol derivatives were incorporated into the sLe<sup>x</sup> mimetics <b>2b-n</b>. For analyzing the relationship of affinity and core conformation, a <sup>1</sup>H NMR structural-reporter-group concept was applied. Thus, the chemical shift of H-C5<sup>Fuc</sup> proved to be a sensitive indicator for the degree of pre-organization of the core of this class of sLe<sup>x</sup> mimetics and therefore could be used to quantify the contribution of the R-groups.
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