Dipp-Pro | 110484-56-5

• 英文名称: Dipp-Pro
• 英文别名: N-diisopropoxyphosphoryl-L-proline；O,O-diisopropyl phosphoryl-Pro；N-(Disopropyloxyphosphoryl)-L-Pro-OH；N-diisopropyloxyphosphoryl-Pro；(2S)-1-di(propan-2-yloxy)phosphorylpyrrolidine-2-carboxylic acid
• CAS: 110484-56-5
• 化学式: C₁₁H₂₂NO₅P
• 分子量: 279.273
• InChiKey: QVGHAHGFQRHMTM-JTQLQIEISA-N

物化性质

• 沸点：
  376.5±52.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  白杨素 、 Dipp-Pro 在 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以63%的产率得到5-hydroxy-4-oxo-2-phenyl-4H-chromen-7-yl (diisopropoxyphosphoryl)-L-prolinate
  参考文献：
  名称：

  磷酰氨基酸白杨素酯的合成

  摘要：

  N-磷酰基氨基酸与白杨素偶联形成磷酰基氨基酸白杨素酯。已经合成了五种新的类似物。所有新合成的白杨素衍生物的结构均通过 ESI-MS、NMR 和 IR 确认。

  DOI：

  10.1080/10426500701793204
• 作为产物：
  描述：

  亚磷酸二异丙酯 、 L-脯氨酸 在 三乙胺 作用下， 以 四氯化碳 、 乙醇 为溶剂， 以92%的产率得到Dipp-Pro
  参考文献：
  名称：

  Synthesis ofN-(Diisopropyloxyphosphoryl)amino Acids and Peptides

  摘要：

  N-(二异丙氧基磷酰基)氨基酸（N-Dipp-氨基酸）是通过二异丙基亚磷酸酯和氨基酸在混合水介质中一步制备得到的。它们可以通过二环己基碳二亚胺或其他活化剂进行活化，用于合成N-(二异丙氧基磷酰基)二肽。

  DOI：

  10.1055/s-1988-27602

文献信息

• A practical preparation of diisopropyl phosphoryl protected amino acids
  作者：K.M.J. Brands、K. Wiedbrauk、J.M. Williams、U.-H. Dolling、P.J. Reider

  DOI：10.1016/s0040-4039(98)02300-4

  日期：1998.12

  N-Diisopropyl phosphoryl protected amino acids can be prepared in high yield and without racemization by slow addition of sodium hypochlorite to a solution of the amino acid and diisopropylphosphite in water while carefully maintaining a constant pH via the addition of sodium hydroxide.

  通过将次氯酸钠缓慢添加到氨基酸和亚磷酸二异丙酯在水中的溶液中，同时通过添加氢氧化钠小心地保持恒定的pH值，可以高产率地制备N-二异丙基磷酸基保护的氨基酸，而没有消旋作用。
• Synthesis, In Vitro Anticancer Evaluation, and Interference with Cell Cycle Progression of N‐Phosphoamino Acid Esters of Zidovudine and Stavudine
  作者：Y. W. Wu、Q. Xiao、Y. Y. Jiang、H. Fu、Y. Ju、Y. F. Zhao

  DOI：10.1081/ncn-200034057

  日期：2004.1.1

  (DIPP) l‐amino acid ester prodrugs of zidovudine (AZT) (3a–3e) and stavudine (d4T) (4a–4e) has been prepared. The activity of these compounds against MCF‐7 cells (human pleural effusion breast adenocarcinoma cell line) and K562 cells (human chronic myeloid leukemia (CML) cell line) was evaluated. In difference from that of AZT amino acid phosphoramidates, the alophatic amino acid esters of AZT were found

  已经制备了一系列齐多夫定 (AZT) (3a-3e) 和司他夫定 (d4T) (4a-4e) 的 N-二异丙基磷酰 (DIPP) l-氨基酸酯前药。评估了这些化合物对 MCF-7 细胞（人胸腔积液乳腺腺癌细胞系）和 K562 细胞（人慢性粒细胞白血病 (CML) 细胞系）的活性。与 AZT 氨基酸氨基磷酸酯不同，AZT 的脂肪族氨基酸酯对 MCF-7 细胞的细胞毒性比芳香族类似物更强。发现 d4T 4b (CC50 = 83 µM) 和 4c (CC50 = 182 µM) 的两种 DIPP-l-氨基酸酯对 K562 细胞的细胞毒性比母体药物更强。研究了 MCF-7 和 K562 细胞周期紊乱，显示当暴露于具有生物活性的 AZT、3a、3b、3c、4b 和 4c 时，在 S 期可检测到阻断，表明它们通过阻断细胞周期进程来抑制细胞生长。与之前的报告一起，目前的研究结果表明 AZT 的抗乳腺癌活性可能是由于阻碍了
• Novel synthesis of steryl esteryl esters from β-sitosterol and <i>N</i>-phosphoryl amino acid under microwave irradiation
  作者：Jinwei Yuan、Liangru Yang、Yongmei Xiao、Lingbo Qu

  DOI：10.1080/10426507.2016.1206102

  日期：2016.10.2

  GRAPHICAL ABSTRACT ABSTRACT Ten novel N-phosphoryl amino acids β-sitosterol esters were synthesized by coupling the N-phosphoryl amino acids with β-sitosterol under microwave irradiation, and their structures were elucidated by IR, NMR, and HR MS. Various reaction conditions including the catalyst, solvent, temperature and time were investigated. Under the optimal conditions, the reaction was finished in

  图形摘要 摘要 通过在微波辐射下将 N-磷酰氨基酸与 β-谷甾醇偶联合成了 10 种新型 N-磷酰氨基酸 β-谷甾醇酯，并通过 IR、NMR 和 HR MS 阐明了它们的结构。研究了各种反应条件，包括催化剂、溶剂、温度和时间。在最佳条件下，在室温下使用 DCC/DMAP 作为催化剂体系，反应在 20 分钟内完成，产率为 60-87%。
• The design, synthesis, and anti-tumor mechanism study of N-phosphoryl amino acid modified resveratrol analogues
  作者：Huachen Liu、Aijun Dong、Chunmei Gao、Chunyan Tan、Hongxia Liu、Xuyu Zu、Yuyang Jiang

  DOI：10.1016/j.bmc.2008.10.022

  日期：2008.12

  A novel series of trans-N-phosphoryl amino acid modified resveratrol analogues were synthesized and evaluated in vitro for their cytotoxic effects against CNE-1 and CNE-2 cell lines. These analogues showed good anti-proliferative activity, among which 8d, 8e, 8j, and 9d displayed much stronger inhibition effect than resveratrol and 8d showed the most potent activity with IC(50) value at 3.45 +/- 0.82 mu M. The antitumor effects of 8d, 8e, 8j, and 9d were due to the induction of apoptosis, confirmed by the DNA fragmentation and flow cytometry analysis using PI (propidium iodide) staining and Annexin-V-FITC/PI staining assay. The PI staining assay also showed that 8d, 8e, 8j, and 9d caused cell cycles arrest at G(0)-G(1) phase which finally led to cell apoptosis. Further mechanism study on compound 8d against CNE-2 cells has shown the PARP cleavage, which is a hallmark of caspase-3 activation, as well as the activation of caspase-9, and the intracellular ROS generation. These results all suggest that 8d induced a mitochondrial-dependent apoptosis pathway. (c) 2008 Elsevier Ltd. All rights reserved.