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

• DOI: 10.3987/com-04-10009
• Publication Date: 2009-03-05T07:31:45Z
• Authors: Tsuyoshi Miura; Shinji Nakahara; Toru Tanaka; Kazuharu Noguchi; Kenji Nozaki; Shuichi Tsuji; Tetsuya Kajimoto
• Keywords: Cytosine

Novel mimics of cytidine 5'-monophosphate-sialic acid (CMP-sialic acid) were designed and synthesized for targeting inhibitors sialyltransferases on the basis phenomenon that tautomerization 5-fluorouracil from lactam to lactim form produces a structure similar cytosine, C-terminal's peptide bond can be bioisoster phosphate group.Since γ-N 1 -(5-fluorouracilyl)-β-hydroxy-α-L-amino acid, key synthetic intermediate, was easily prepared using enzyme-catalyzed aldol reaction, synthesis CMP-sialic attained in short step.Sialyl oligosaccharides, which sialic acids link non-reducing ends glycoconjugates cell surfaces, play important roles differentiation, immune responses, bacterial viral infections, other cell-cell recognition events. Therefore, toward transfer 5'-phospho-β-D-ribose-sialic acid: 1) galactose or residues oligosaccharides would excellent candidates as anti-inflammatory agents, anti-metastastic agents auto-immune diseases. 2Despite number analogs being few them exhibited potent inhibitory activities, routes required very tedious procedures provide sufficient amount HN