6-N-acetyl-2',3'-di-O-benzoyl-8-oxoadenosine 5'-[2-(trimethylsilyl)ethyl N,N-diisopropylphosphoramidite] | 297731-15-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 6-N-acetyl-2',3'-di-O-benzoyl-8-oxoadenosine 5'-[2-(trimethylsilyl)ethyl N,N-diisopropylphosphoramidite]
• 英文别名: [(2R,3R,4R,5R)-5-(6-acetamido-8-oxo-7H-purin-9-yl)-4-benzoyloxy-2-[[[di(propan-2-yl)amino]-(2-trimethylsilylethoxy)phosphanyl]oxymethyl]oxolan-3-yl] benzoate
• CAS: 297731-15-8
• 化学式: C₃₇H₄₉N₆O₉PSi
• 分子量: 780.89
• InChiKey: OXUZESUSZWSKQH-SYBXZEODSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.14
• 重原子数：
  54
• 可旋转键数：
  18
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  171
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  N-[4,4',4''-tris(benzoyloxy)trityl]-L-prolinamide 、 6-N-acetyl-2',3'-di-O-benzoyl-8-oxoadenosine 5'-[2-(trimethylsilyl)ethyl N,N-diisopropylphosphoramidite] 在 5-(3,5-dinitrophenyl)-1H-tetrazole 、 叔丁基过氧化氢 作用下， 以 乙腈 为溶剂， 反应 0.25h， 生成 (2S)-N-[[(2R,3R,4R,5R)-3,4-dibenzoyloxy-5-[8-hydroxy-6-(1-hydroxyethylideneamino)purin-9-yl]oxolan-2-yl]methoxy-oxido-(2-trimethylsilylethoxy)phosphaniumyl]-1-[tris(4-benzoyloxyphenyl)methyl]pyrrolidine-2-carboximidic acid
  参考文献：
  名称：

  膦酰胺及其相关化合物的首次合成及其抗癌活性。

  摘要：

  本文描述了膦酰胺和膦嘧啶B的首次合成，即由8-氧代腺苷和L-脯氨酸组成的核苷酸抗生素，它们通过独特的N-酰基氨基磷酸酯键连接。膦酰胺在N-酰基氨基磷酸酯键的磷原子上具有尚未确定的手性中心。磷肌苷B是一种脱磷的磷肌苷衍生物，在磷上没有手性。在5-（3,5-二硝基苯基）-1H-四唑存在下，N-乙酰基-8-氧代腺苷5'-O-亚磷酰胺衍生物与N-保护的脯氨酰胺反应成功地合成了肌苷B。通过使用叔丁氧羰基（Boc）基团可以成功合成膦嘧啶 发现它被选择性地引入到8-氧代腺苷的7-NH官能团中，并由于其空间效应而以未保护的6-氨基未被磷酸化的方式用作假保护基团。8-氧代腺苷5'-亚磷酰胺衍生物与N-三苯甲基脯氨酰胺的最终偶联反应，然后完全脱保护，得到膦酰胺及其非对映异构体的混合物。非对映异构体的（13）C NMR光谱表明，缓慢洗脱的非对映异构体1b是天然存在的膦酰胺。通过MTT分析评价了膦肌苷1b，其非对

  DOI：

  10.1021/jo016176g
• 作为产物：
  描述：

  8-氧腺苷 在 吡啶 、 4-二甲氨基吡啶 、 pyridine amine 、 二异丙基铵盐四氮唑 、 四丁基氟化铵 、 sodium acetate 、 溶剂黄146 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 38.5h， 生成 6-N-acetyl-2',3'-di-O-benzoyl-8-oxoadenosine 5'-[2-(trimethylsilyl)ethyl N,N-diisopropylphosphoramidite]
  参考文献：
  名称：

  Synthesis and antitumor activities of phosmidosine A and its N-acetylated derivative

  摘要：

  A new antitumor active phosmidosine A, which was isolated from Streptomyces sp., was successfully synthesized by a series of reactions involving construction of the N-acyl phosphoramidate linkage which was achieved by the reaction of the 5'-O-phosphoramidite derivative with a prolinamide derivative in the presence of 5-(3,5-dinitrophenyl)-1H-tetrazole. The growth inhibitory effect of phosmidosine A and its N-acetyl analog on the various human cell lines was examined. These results showed that both compounds have a significant growth inhibitory activity and that the 6-amino group is not required for the growth inhibitory activity of phosmidosine A. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(00)00926-6

文献信息

• First Synthesis and Anticancer Activity of Phosmidosine and Its Related Compounds
  作者：Tomohisa Moriguchi、Norio Asai、Kazuhisa Okada、Kohji Seio、Takuma Sasaki、Mitsuo Sekine

  DOI：10.1021/jo016176g

  日期：2002.5.1

  the presence of 5-(3,5-dinitrophenyl)-1H-tetrazole. The successful synthesis of phosmidosine was achieved by use of a tert-butoxycarbonyl (Boc) group, which was found to be selectively introduced into the 7-NH function of 8-oxoadenosine and to serve as a pseudo-protecting group due to its steric effect in such manner that the unmasked 6-amino group was not phosphitylated. Final coupling reaction of the

  本文描述了膦酰胺和膦嘧啶B的首次合成，即由8-氧代腺苷和L-脯氨酸组成的核苷酸抗生素，它们通过独特的N-酰基氨基磷酸酯键连接。膦酰胺在N-酰基氨基磷酸酯键的磷原子上具有尚未确定的手性中心。磷肌苷B是一种脱磷的磷肌苷衍生物，在磷上没有手性。在5-（3,5-二硝基苯基）-1H-四唑存在下，N-乙酰基-8-氧代腺苷5'-O-亚磷酰胺衍生物与N-保护的脯氨酰胺反应成功地合成了肌苷B。通过使用叔丁氧羰基（Boc）基团可以成功合成膦嘧啶 发现它被选择性地引入到8-氧代腺苷的7-NH官能团中，并由于其空间效应而以未保护的6-氨基未被磷酸化的方式用作假保护基团。8-氧代腺苷5'-亚磷酰胺衍生物与N-三苯甲基脯氨酰胺的最终偶联反应，然后完全脱保护，得到膦酰胺及其非对映异构体的混合物。非对映异构体的（13）C NMR光谱表明，缓慢洗脱的非对映异构体1b是天然存在的膦酰胺。通过MTT分析评价了膦肌苷1b，其非对
• Synthesis and antitumor activities of phosmidosine A and its N-acetylated derivative
  作者：Tomohisa Moriguchi、Norio Asai、Takeshi Wada、Kohji Seio、Takuma Sasaki、Mitsuo Sekine

  DOI：10.1016/s0040-4039(00)00926-6

  日期：2000.7

  A new antitumor active phosmidosine A, which was isolated from Streptomyces sp., was successfully synthesized by a series of reactions involving construction of the N-acyl phosphoramidate linkage which was achieved by the reaction of the 5'-O-phosphoramidite derivative with a prolinamide derivative in the presence of 5-(3,5-dinitrophenyl)-1H-tetrazole. The growth inhibitory effect of phosmidosine A and its N-acetyl analog on the various human cell lines was examined. These results showed that both compounds have a significant growth inhibitory activity and that the 6-amino group is not required for the growth inhibitory activity of phosmidosine A. (C) 2000 Elsevier Science Ltd. All rights reserved.