5′-[benzyl-N,N-bis(1-methylethyl)phosphoramidite]-N⁴-2′,3′-O-tris-benzyloxycarbonyl cytidine | 1120346-92-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: 5′-[benzyl-N,N-bis(1-methylethyl)phosphoramidite]-N⁴-2′,3′-O-tris-benzyloxycarbonyl cytidine
• 英文别名: 5'-(benzyl-N,N-bis(1-methylethyl)phosphoramidite)-N⁴,2',3'-O-tris-benzyloxycarbonylcytidine；benzyl [(2R,3R,4R,5R)-2-[[[di(propan-2-yl)amino]-phenylmethoxyphosphanyl]oxymethyl]-5-[2-oxo-4-(phenylmethoxycarbonylamino)pyrimidin-1-yl]-4-phenylmethoxycarbonyloxyoxolan-3-yl] carbonate
• CAS: 1120346-92-0
• 化学式: C₄₆H₅₁N₄O₁₂P
• 分子量: 882.904
• InChiKey: JOXHUVASFCNRTC-RGXHQTEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  63
• 可旋转键数：
  24
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  173
• 氢给体数：
  1
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  5′-[benzyl-N,N-bis(1-methylethyl)phosphoramidite]-N⁴-2′,3′-O-tris-benzyloxycarbonyl cytidine 在 四氮唑 、 水 作用下， 以 乙腈 为溶剂， 反应 0.08h， 生成
  参考文献：
  名称：

  AP（V）–N活化核苷多磷酸盐合成的策略

  摘要：

  已经开发了由4，5-二氰基咪唑（DCI）促进的受保护的核苷5'-磷酸哌啶酸酯合成核苷5'-三磷酸酯（NTPs）和核苷5'-二磷酸酯（NDP）的通用且高产率的方法。31 P NMR示踪实验表明，顺序的脱保护和偶联反应非常干净。磷酸哌啶酯对DCI促进的NTP / NDP合成显示出优于常规磷酸吗啉酸酯的反应性。实验结果表明，取决于焦磷酸盐和磷酸盐的不同亲核性，DCI激活的机制对于NTP和NDP合成可能是独特的。

  DOI：

  10.1021/jo4011156
• 作为产物：
  描述：

  胞苷 在 吡啶 、 四氮唑 、 4-二甲氨基吡啶 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 58.0h， 生成 5′-[benzyl-N,N-bis(1-methylethyl)phosphoramidite]-N⁴-2′,3′-O-tris-benzyloxycarbonyl cytidine
  参考文献：
  名称：

  Transition State-Based Sialyltransferase Inhibitors: Mimicking Oxocarbenium Ion by Simple Amide

  摘要：

  In the new transition-state based sialyltransferase inhibitors, an amide group was placed at the corresponding C-2 position of CMP-sialic acid to mimic the geometry and charge distribution in the transition state, and simple aromatic or aliphatic rings were used instead of the sialic acid moiety. All synthetic compounds exhibited excellent a(2-6)-sialyltransferase inhibition, resulting in up to a 2600-fold higher affinity for the enzyme than CMP-Neu5Ac, suggesting that amide is a key element for simulating transition-state

  DOI：

  10.1021/acs.jmedchem.6b01644

文献信息

• Highly Substituted Cyclopentane–CMP Conjugates as Potent Sialyltransferase Inhibitors
  作者：Wenming Li、Youhong Niu、De-Cai Xiong、Xiaoping Cao、Xin-Shan Ye

  DOI：10.1021/acs.jmedchem.5b01181

  日期：2015.10.22

  Sialylconjugates on cell surfaces are involved in many biological events such as cellular recognition, signal transduction, and immune response. It has been reported that aberrant sialylation at the nonreducing end of glycoconjugates and overexpression of sialyltransferases (STs) in cells are correlated with the malignance, invasion, and metastasis of tumors. Therefore, inhibitors of STs would provide valuable leads for the discovery of antitumor drugs. On the basis of the transition state of the enzyme-catalyzed sialylation reaction, we proposed that the cydopentane skeleton in its two puckered conformations might mimic the planar structure of the donor (CMP-Neu5Ac) in the transition state. A series of cydopentane-containing compounds were designed and synthesized by coupling different cydopentane alpha-hydroxyphosphonates with cytidine phosphoramidite. Their inhibitory activities against recombinant human ST6Gal-I were assayed, and a potent inhibitor 481 with a K-i of 0.028 +/- 0.006 mu M was identified. The results show that the cydopentanoid-type compounds could become a new type of sialyltransferase inhibitors as biological probes or drug leads.