2',3'-O,N⁴-tribenzoyl-5'-O-tert-butyldiphenylsilyl cytidine | 302346-90-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 2',3'-O,N⁴-tribenzoyl-5'-O-tert-butyldiphenylsilyl cytidine
• 英文别名: 2',3'-O,N(4)-tribenzoyl-5'-O-tert-butyldiphenylsilyl cytidine；[(2R,3R,4R,5R)-5-(4-benzamido-2-oxopyrimidin-1-yl)-4-benzoyloxy-2-[[tert-butyl(diphenyl)silyl]oxymethyl]oxolan-3-yl] benzoate
• CAS: 302346-90-3
• 化学式: C₄₆H₄₃N₃O₈Si
• 分子量: 793.948
• InChiKey: LJTDHHACTIQKEA-HFUPZSMGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.42
• 重原子数：
  58.0
• 可旋转键数：
  12.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  135.05
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  2',3'-O,N⁴-tribenzoyl-5'-O-tert-butyldiphenylsilyl cytidine 在 四丁基氟化铵 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以95%的产率得到N,2',3'-O-tribenzoylcytidine
  参考文献：
  名称：

  Synthesis and Characterization of an Anomeric Sulfur Analogue of CMP-Sialic Acid

  摘要：

  alpha-2,3-Sialyltransferase catalyzes the transfer of sialic acid from CMP-sialic acid (1) to a lactose acceptor. An analogue of 1 was synthesized in which the anomeric oxygen atom was replaced with a sulfur atom (1S). The key step in the synthesis of 1S was a tetrazole-promoted coupling of a cytidine-5'-phosphoramidite with a glycosyl thiol of a protected sialic acid. Compounds 1 and 1S were characterized for their activity in a sialyl transfer assay. The rate of solvolysis in aqueous buffer of analogue 1S was 50-fold slower than that of 1. Analogue 1S was found to be substrate for alpha-2,3-sialyltransferase. The K-m of 1S was just 3-fold higher than that of 1, while the k(cat) of 1S was 2 orders of magnitude lower compared to 1.

  DOI：

  10.1021/jo000646+
• 作为产物：
  描述：

  胞苷 在 咪唑 作用下， 以 吡啶 、 N,N-二甲基甲酰胺 为溶剂， 反应 49.0h， 生成 2',3'-O,N⁴-tribenzoyl-5'-O-tert-butyldiphenylsilyl cytidine
  参考文献：
  名称：

  Synthesis and Characterization of an Anomeric Sulfur Analogue of CMP-Sialic Acid

  摘要：

  alpha-2,3-Sialyltransferase catalyzes the transfer of sialic acid from CMP-sialic acid (1) to a lactose acceptor. An analogue of 1 was synthesized in which the anomeric oxygen atom was replaced with a sulfur atom (1S). The key step in the synthesis of 1S was a tetrazole-promoted coupling of a cytidine-5'-phosphoramidite with a glycosyl thiol of a protected sialic acid. Compounds 1 and 1S were characterized for their activity in a sialyl transfer assay. The rate of solvolysis in aqueous buffer of analogue 1S was 50-fold slower than that of 1. Analogue 1S was found to be substrate for alpha-2,3-sialyltransferase. The K-m of 1S was just 3-fold higher than that of 1, while the k(cat) of 1S was 2 orders of magnitude lower compared to 1.

  DOI：

  10.1021/jo000646+

文献信息

• Selective Inhibitors of Bacterial Phosphopantothenoylcysteine Synthetase
  作者：James D. Patrone、Jiangwei Yao、Nicole E. Scott、Garry D. Dotson

  DOI：10.1021/ja906537f

  日期：2009.11.18

  Bacterial phosphopantothenotycysteine synthetase (PPCS) catalyzes the formation of phosphopantothenoylcysteine (PPC) from (R)-phosphopantothenate, L-cysteine, and cytidine-5'-triphosphate (CTP) and has been shown to be essential for growth and survival. The reaction proceeds through a phosphopantothenoyl cytidylate, mixed anhydride intermediate. Both structural and kinetic characterization studies on PPCS have shown differences in the nucleobase binding site between the bacterial and human enzyme. We report for the first time the design and synthesis of mimics of the phosphopantothenoyl cytidylate, which proved to be potent inhibitors of PPCS. These compounds were evaluated in vitro against PPCS from human and several species of bacteria and showed marked selectivity (up to 1000-fold) toward the bacterial. enzymes. A phosphodiester intermediate mimic was the most potent of the compounds synthesized and displayed stow-onset, tight-binding kinetics toward E. faecalis PPCS.