Synthesis of CMP-sialic Acid Mimics That Have 5-Fluorouracil for Cytosine and the C-Terminal's Peptide Bond for the Phosphate Group: Targeting Inhibitors of Sialyltransferases

Novel mimics of cytidine 5'-monophosphate-sialic acid (CMP-sialic acid) were designed and synthesized for targeting inhibitors of sialyltransferases on the basis of the phenomenon that the tautomerization of 5-fluorouracil from the lactam to the lactim form produces a structure similar to that of cytosine, and the C-terminal's peptide bond can be a bioisoster of a phosphate group. Since y-N 1 -(5-fluorouracilyl)-β-hydroxy-a-L-amino acid, a key synthetic intermediate, was easily prepared using the enzyme-catalyzed aldol reaction, the synthesis of the mimics of the CMP-sialic acid was attained in a short step.