N-[diethoxyphosphoryl(naphthalen-2-yl)methyl]-1-naphthalen-2-ylmethanimine | 909722-69-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-[diethoxyphosphoryl(naphthalen-2-yl)methyl]-1-naphthalen-2-ylmethanimine
• CAS: 909722-69-6
• 化学式: C₂₆H₂₆NO₃P
• 分子量: 431.471
• InChiKey: NAGAZNWAMYKLCV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.38
• 重原子数：
  31.0
• 可旋转键数：
  8.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  47.89
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  N-[diethoxyphosphoryl(naphthalen-2-yl)methyl]-1-naphthalen-2-ylmethanimine 在 盐酸 作用下， 以 乙醚 为溶剂， 反应 2.0h， 生成 Diethoxyphosphoryl(naphthalen-2-yl)methanamine;hydrochloride
  参考文献：
  名称：

  Novel Coumarin-Containing Aminophosphonatesas Antitumor Agent: Synthesis, Cytotoxicity, DNA-Binding and Apoptosis Evaluation

  摘要：

  合成了一系列含有香豆素结构的α-氨基膦酸酯类新化合物，并评估了它们对体外人结直肠癌（HCT-116）、人鼻咽癌（人KB）和人肺腺癌（MGC-803）细胞系的抗癌活性。与7-羟基-4-甲基香豆素（4-MU）相比，大多数衍生物显示出增强的抗癌活性。化合物8j（二乙基1-（3-（4-甲基-2-氧-2H-色烯-7-基氧）丙酰胺基）-1-苯乙基膦酸酯），对HCT-116细胞系的IC50值为8.68 μM，是其未取代母体化合物的约12倍。机制研究表明，8c、8d、8f和8j通过诱导G1期细胞周期阻滞来实现细胞凋亡。此外，进一步揭示了化合物8j诱导HCT-116细胞凋亡的机制，表明化合物8j通过激活caspase-9和caspase-3引起细胞凋亡，并改变抗凋亡和促凋亡蛋白。DNA结合实验表明，某些衍生物通过嵌插与DNA结合。结果似乎暗示了香豆素和氨基膦酸酯之间存在重要的协同效应，这可能有助于氨基膦酸酯部分的强螯合特性。

  DOI：

  10.3390/molecules200814791
• 作为产物：
  描述：

  2-萘甲醛 、 亚磷酸二乙酯 在 ammonium hydroxide 作用下， 反应 5.0h， 生成 N-[diethoxyphosphoryl(naphthalen-2-yl)methyl]-1-naphthalen-2-ylmethanimine
  参考文献：
  名称：

  TMSCl-Promoted Addition of Diethyl Phosphite to an Imine for the Synthesis of Bis[1-diethoxyphosphorylalkyl]amines

  摘要：

  已开发出一种简便的制备双[1-二乙氧基膦酰基烷基]胺类化合物的方法。将芳香醛与氨反应，再与二乙基亚磷酸酯反应，得到二乙基芳基[(芳基亚甲基)氨基]甲基膦酸酯，这些化合物在氯三甲基硅烷存在下可轻松与二乙基亚磷酸酯反应，生成双[1-二乙氧基膦酰基烷基]胺。该方法简便、快速且产率高，适合从简单原料合成双[1-二乙氧基膦酰基烷基]胺。

  DOI：

  10.1055/s-2006-942432

文献信息

• A simple and convenient procedure for the synthesis of 1-aminophosphonates from aromatic aldehydes
  作者：Babak Kaboudin、Khavar Moradi

  DOI：10.1016/j.tetlet.2005.03.037

  日期：2005.4

  A simple, efficient, possible industrial process has been developed for the synthesis of 1-aminophosphonic acids from simple starting materials. As described below, treatment of aromatic aldehydes with ammonia and reaction with diethyl phosphite gives diethyl N-(arylmethylene)-1-aminoaryl methylphosphonates, which can be easily hydrolyzed to diethyl 1-aminoarylmethylphosphonates. This method is easy

  已经开发了一种简单，有效，可能的工业方法，用于从简单的起始原料合成1-氨基膦酸。如下所述，用氨处理芳族醛并与亚磷酸二乙酯反应得到N-（芳基亚甲基）-1-氨基芳基甲基膦酸二乙酯，其可以容易地水解为1-氨基芳基甲基膦酸二乙酯。从简单的起始原料合成1-氨基烷基膦酸酯的方法简便，快速且产率高。
• Surface-Mediated Solid Phase Reactions: A Simple and New Method for the Synthesis of<i>α</i>-Aminophosphonates under Solvent-Free Conditions
  作者：Babak Kaboudin

  DOI：10.1246/cl.2001.880

  日期：2001.9

  Alumina-supported ammonium formate was found to be an efficient reagent for the synthesis of 1-aminophosphonates from aldehydes and diethyl phosphite. This method is an easy, rapid and high-yieldin...

  发现氧化铝负载的甲酸铵是从醛和亚磷酸二乙酯合成 1-氨基膦酸酯的有效试剂。这种方法是一种简单、快速和高产...
• A Novel Synthesis of Diethyl 1-Aminoarylmethylphosphonates on the Surface of Alumina
  作者：A.R Sardarian*、B Kaboudin

  DOI：10.1016/s0040-4039(97)00396-1

  日期：1997.4

  A novel route has been devised for the preparation of a series of diethyl 1-aminoarylmethylphosphonates. The route involves facile reaction among aromatic aldehydes, diethyl hydrogen phosphite and HMDS on the surface of alumina. (C) 1997 Published by Elsevier Science Ltd.
• Coumarin-containing aminophosphonates bridged with chiral side chain: synthesis and influence of chirality on cytotoxicity and DNA binding
  作者：Ya-Jun Li、Man-Yi Ye、Ri-Zhen Huang、Gui-Yang Yao、Ying-Ming Pan、Zhi-Xin Liao、Heng-Shan Wang

  DOI：10.1007/s00044-013-0899-3

  日期：2014.6

  A series of novel coumarin-containing alpha-aminophosphonates with two chiral centers were synthesized and a single-crystal structure of compound 8g (8g', (R)-diethyl ((S)-2-(4-methyl-2-oxo-2H-chromen-7-yloxy)propanamido)(2-bromophenyl)methylphosphonate) was obtained. The in vitro antitumor activities of compound 8a-8g' against human pulmonary carcinoma cell line (A549), human nasopharyngeal carcinoma (human KB), and human lung adenocarcinoma (MGC-803) cell lines were evaluated. Some compounds showed relatively high cytotoxicity. Compared with 8g, 8g' exhibited an improved activity against three tumor cells, which was evidenced by the IC50 that was four- to five-fold lower than those for 8g. The influence of chirality was also observed in DNA-binding assay of 8g and 8g'. 8g' exhibited higher binding constant (1.96 x 10(3) M-1) as compared to 8g (1.69 x 10(3) M-1).
• Synthesis and antitumor activities of novel rhein α-aminophosphonates conjugates
  作者：Gui-yang Yao、Man-yi Ye、Ri-zhen Huang、Ya-jun Li、Ying-ming Pan、Qing Xu、Zhi-Xin Liao、Heng-shan Wang

  DOI：10.1016/j.bmcl.2013.12.030

  日期：2014.1

  Several rhein alpha-aminophosphonates conjugates (5a-5q) were synthesized and evaluated for in vitro cytotoxicity against HepG-2, CNE, Spca-2, Hela and Hct-116 cell lines. Some compounds showed relatively high cytotoxicity. Especially, compound 5i exhibited the strongest cytotoxicity against Hct-116 cells (IC50 was 5.32 mu M). All the synthesized compounds exhibited low cytotoxicity against HUVEC cells. The mechanism of compound 5i was preliminarily investigated by Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining and flow cytometry, which indicated that the compound 5i induced apoptosis in Hct-116 cancer cells. Cell cycle analysis showed that these compound 5i mainly arrested Hct-116 cells in G1 stage. The effects of 5i on the activation of caspases expression indicated that 5i might induce apoptosis via the membrane death receptor pathways. In addition, the binding properties of a model analog 5i to DNA were investigated by methods (UV-vis, fluorescence, CD spectroscopy and FRET-melting) in compare with that of rhein. Results indicated that 5i showed moderate ability to interact ct-DNA. (C) 2013 Elsevier Ltd. All rights reserved.