4-acetyloxybenzyl bis(N,N-diisopropyl)phosphoramidite | 171284-20-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 英文名称: 4-acetyloxybenzyl bis(N,N-diisopropyl)phosphoramidite
• 英文别名: acetoxybenzyl bis(diisopropylamino)phosphoramidite；4-[({bis[bis(propan-2-yl)amino]phosphanyl}oxy)methyl]phenyl acetate；4-acetoxybenzyl N,N,N’,N’-tetraisopropylphosphoramidite；[4-[Bis[di(propan-2-yl)amino]phosphanyloxymethyl]phenyl] acetate
• CAS: 171284-20-1
• 化学式: C₂₁H₃₇N₂O₃P
• 分子量: 396.51
• InChiKey: RGOJQCHLFOPSQE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  27
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  42
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-acetyloxybenzyl bis(N,N-diisopropyl)phosphoramidite 在 4,5-二氰基咪唑 作用下， 以 水 、 乙腈 为溶剂， 反应 0.75h， 生成 [4-[[(4-acetyloxyphenyl)methoxy-[hydroxy-[[(2S,5R)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-2,5-dihydrofuran-2-yl]methoxy]phosphoryl]oxyphosphoryl]oxymethyl]phenyl] dodecanoate;azane
  参考文献：
  名称：

  Nucleoside Diphosphate Prodrugs: Nonsymmetric DiPPro-Nucleotides

  摘要：

  Nonsymmetric DiPPro-nucleotides are described as nucleoside diphosphate (NDP) delivery systems. The concept is to attach different bis(acyloxybenzyl) moieties at the beta-phosphate moiety of a NDP. DiPPro compounds bearing two alkanoylbenzyl residues and DiPPro compounds bearing an alkanoylbenzyl or a benzoylbenzyl group as bioreversible prodrug moieties were studied. Compounds bearing short chain alkanoyl esters led to a fast hydrolysis by chemical or enzymatic means. The ester group in the second prodrug group comprised a long lipophilic aliphatic or an aromatic residue. The lipophilicity of this group enabled the prodrug to penetrate the cell membrane. The introduction of two different groups allowed a controlled stepwise removal of the prodrug moieties to achieve a highly selective delivery of the ND? in CEM cell extracts. The compounds were highly active against HIV even in thymidine ldnase-deficient CEM cells. Thus, the compounds, although charged at the a-phosphate group, were taken up by the cells and released NDPs.

  DOI：

  10.1021/acs.jmedchem.5b00737
• 作为产物：
  描述：

  4-乙酰氧基苄醇 、 双二异丙基氨基氯化磷 在 三乙胺 作用下， 以 乙醚 为溶剂， 生成 4-acetyloxybenzyl bis(N,N-diisopropyl)phosphoramidite
  参考文献：
  名称：

  γ-酮苄基修饰的核苷三磷酸前药作为潜在的抗病毒药

  摘要：

  核苷逆转录酶抑制剂的抗病毒活性通常受到磷酸化不足的阻碍。提出了核苷三磷酸酯类似物，其中γ-磷酸酯被非生物可逆的亲脂性4-烷基酮苄基部分共价修饰。有趣的是，使用人类免疫缺陷病毒逆转录酶（HIV-RT）和三种DNA聚合酶进行引物延伸分析显示，这些γ-修饰的核苷三磷酸作为HIV-RT的底物具有很高的选择性，而事实证明它们不是DNA-的非底物。聚合酶α，β和γ。与d4TTP相比，γ-修饰的d4TTP在细胞提取物中表现出对去磷酸化的高抗性。制备了这些γ-酮苄基核苷三磷酸的一系列酰氧基苄基前药。目的是在细胞内递送稳定的γ-修饰的三磷酸核苷，以增加此类化合物在感染细胞与未感染细胞中起作用的选择性。γ-酮苄基-d4TTP的传递已在T淋巴细胞细胞提取物中得到证实。在感染的CEM / 0细胞培养物中，前药是有效的HIV-1 / 2抑制剂，更重要的是在胸苷激酶缺陷型CD4中+ T细胞。

  DOI：

  10.1021/acs.jmedchem.0c01293

文献信息

• Synthesis and Cellular Labeling of Caged Phosphatidylinositol Derivatives
  作者：Rainer Müller、Mevlut Citir、Sebastian Hauke、Carsten Schultz

  DOI：10.1002/chem.201903704

  日期：2020.1.7

  Phosphatidylinositol (PI) is the biosynthetic precursor for seven phosphoinositides, important signaling lipids in cells. A membrane-permeant caged PI derivative featuring a photo-removable coumarinyl group masking the negative charge of the phosphate, as well as two enzymatically removable butyrate esters for increased lipophilicity and for preventing phosphate migration, were synthesized. Rapid cell

  磷脂酰肌醇（PI）是7种磷酸肌醇的生物合成前体，这是细胞中重要的信号脂质。合成了具有光可去除香豆素基团的膜渗透性笼状PI衍生物，该衍生物可掩蔽磷酸的负电荷，以及两种可酶去除的丁酸酯，可增加亲脂性并防止磷酸盐迁移。通过可光交联的二嗪胺，然后通过点击化学使荧光团附着，证明了固定细胞中的快速细胞进入和细胞标记。使用该技术，我们发现多功能笼状PI衍生物主要位于内膜，但在解开后迅速变为质膜。因此，
• Prometabolites of 5-Diphospho-<i>myo</i>-inositol Pentakisphosphate
  作者：Igor Pavlovic、Divyeshsinh T. Thakor、Laurent Bigler、Miranda S. C. Wilson、Debabrata Laha、Gabriel Schaaf、Adolfo Saiardi、Henning J. Jessen

  DOI：10.1002/anie.201503094

  日期：2015.8.10

  involves the generation of precursors in which the negative charges are masked with biolabile groups. A PP‐InsPy prometabolite would require twelve to thirteen biolabile groups, which need to be cleaved by cellular enzymes to release the parent molecules. Such densely modified prometabolites of phosphate esters and anhydrides have never been reported to date. This study discloses the synthesis of such

  二磷酸肌醇磷酸酯 (PP-InsPy )是一类重要的细胞信使。到目前为止，还没有将 PP-InsP y转运到活细胞中的方法。由于其高负电荷密度，PP-InsP y不会穿过细胞膜。规避这个问题的策略涉及产生前体，其中负电荷被生物不稳定基团掩盖。PP-InsP y前代谢物需要 12 到 13 个生物不稳定基团，这些基团需要被细胞酶切割以释放母体分子。迄今为止，从未报道过磷酸酯和酸酐的这种密集修饰的前代谢物。该研究公开了此类试剂的合成以及通过凝胶电泳分析它们在组织匀浆中的代谢。乙酰氧基苄基保护的系统能够在几分钟内在哺乳动物细胞/组织匀浆中释放 5-PP-InsP 5，并可用于在细胞内释放 5-PP-InsP 5。这些分子将作为开发研究 PP-InsP y生理学所需的基本工具的平台。
• Synthesis, Bioactivation and Anti-HIV Activity of 4-Acyloxybenzyl<i>bis</i>(Nucleosid-5′-yl) Phosphates
  作者：Anne Routledge、Ian Walker、Sally Freeman、Alan Hay、Naheed Mahmood

  DOI：10.1080/15257779508009491

  日期：1995.9

  4-Acyloxybenzyl bis(nucleosid-5'-yl) phosphates 7a-c and 9a-c were prepared as potential prodrugs of the anti-HIV nucleosides 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxyinosine (ddI) or their 5'-monophosphates.The anti-HIV activities of these triesters were determined in two T-cell lines. In a C8165 cell line they displayed activities comparable to and in some cases superior to AZT, but they also exhibited an increase in cytotoxicity. In a thymidine kinase deficient JM T-cell line the activity was reduced but was still superior to AZT. In the presence of porcine liver carboxyesterase (PLCE), triester 7b biodegrades to the diester 10 which, with phosphodiesterase, gives initially AZT monophosphate 3 and AZT.