(4S)-4-azido-5-tert-butoxy-5-oxopentanoic acid | 473430-10-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (4S)-4-azido-5-tert-butoxy-5-oxopentanoic acid
• 英文别名: (S)-4-azido-5-(tert-butoxy)-5-oxopentanoic acid；L-azidoglutamic acid mono-tert-butyl ester；α-azido L-glutamic acid α-tert-butyl ester；(4S)-4-azido-5-[(2-methylpropan-2-yl)oxy]-5-oxopentanoic acid
• CAS: 473430-10-3
• 化学式: C₉H₁₅N₃O₄
• 分子量: 229.236
• InChiKey: DGSYKROGSCDGNR-LURJTMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  78
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (4S)-4-azido-5-tert-butoxy-5-oxopentanoic acid 在 三氟乙酸 作用下， 反应 2.0h， 生成 (S)-2-叠氮戊二酸
  参考文献：
  名称：

  明亮，“可点击”的卟啉，用于在环境光下可视化氧合

  摘要：

  已经开发了一组新的“可点击的”和发光明亮的金属卟啉，以肉眼可视化环境光下的氧合。这些炔基封端的化合物可通过叠氮化物-炔烃点击化学快速而简便地合成氧敏感树状聚合物。由于吸收最大值与常见的商用激光源的波长重叠，因此它们很容易应用于组织氧合的生物医学成像。描述了一种有效的合成方法，该方法具有稳定的三甲基乙酰基（新戊酰基）保护基，可用于制备。包含新的，点击合成的卟啉树枝状大分子的涂有液体的绷带已用于绘制离体猪皮肤烧伤模型的氧合图。

  DOI：

  10.1002/anie.201506847
• 作为产物：
  描述：

  1-叔丁基 L-谷氨酸 在 copper(ll) sulfate pentahydrate 、 triflic azide 、 potassium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 以100%的产率得到(4S)-4-azido-5-tert-butoxy-5-oxopentanoic acid
  参考文献：
  名称：

  Design and structure activity relationship of tumor-homing histone deacetylase inhibitors conjugated to folic and pteroic acids

  摘要：

  Histone deacetylase (HDAC) inhibition has recently emerged as a novel therapeutic approach for the treatment of various pathological conditions including cancer. Currently, two HDAC inhibitors (HDACi) - Vorinostat and Romidepsin - have been approved for the treatment of cutaneous T-cell lymphoma. However, HDACi remain ineffective against solid tumors and are associated with adverse events including cardiotoxicity. Targeted delivery may enhance the therapeutic indices of HDACi and enable them to be efficacious against solid tumors. We showed herein that morphing of folic and pteroic acids into the surface recognition group of HDACi results in hydroxamate and benzamide HDACi which derived tumor homing by targeting folate receptor (FR), a receptor commonly overexpressed in solid tumors. We observed a correlation between the potency of HDAC1 inhibition and cytotoxicity as only the potent pteroate hydroxamates, 11d and 11e, displayed antiproliferative activity against two representative FR-expression cancer cells. Our observation further supports the previous results which suggest that for a drug to be successfully targeted using the FR, it must be extremely potent against its primary target as the FR has a low delivery efficiency. Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2015.04.014

文献信息

• A New Tri-Orthogonal Strategy for Peptide Cyclization
  作者：Lundquist、Jeffrey C. Pelletier

  DOI：10.1021/ol026416u

  日期：2002.9.1

  A solid phase tri-orthogonal protection/cleavage strategy that uses acidic, basic, and neutral conditions is described. Strategically protected alpha-azido-gamma-9-fluorenylmethyl-L-glutamate (1) and alpha-azido-epsilon-N-Fmoc-L-lysine (2) were incorporated into growing peptides on Wang resin using a novel azide protection strategy. These residues, separated by 1-3 monomers, were deprotected at the side chains and cyclized via lactam formation. The N-terminus was further functionalized to extend the chain. This method represents a straightforward protocol for peptide cyclization on solid support.
• Design and structure activity relationship of tumor-homing histone deacetylase inhibitors conjugated to folic and pteroic acids
  作者：Quaovi H. Sodji、James R. Kornacki、John F. McDonald、Milan Mrksich、Adegboyega K. Oyelere

  DOI：10.1016/j.ejmech.2015.04.014

  日期：2015.5

  Histone deacetylase (HDAC) inhibition has recently emerged as a novel therapeutic approach for the treatment of various pathological conditions including cancer. Currently, two HDAC inhibitors (HDACi) - Vorinostat and Romidepsin - have been approved for the treatment of cutaneous T-cell lymphoma. However, HDACi remain ineffective against solid tumors and are associated with adverse events including cardiotoxicity. Targeted delivery may enhance the therapeutic indices of HDACi and enable them to be efficacious against solid tumors. We showed herein that morphing of folic and pteroic acids into the surface recognition group of HDACi results in hydroxamate and benzamide HDACi which derived tumor homing by targeting folate receptor (FR), a receptor commonly overexpressed in solid tumors. We observed a correlation between the potency of HDAC1 inhibition and cytotoxicity as only the potent pteroate hydroxamates, 11d and 11e, displayed antiproliferative activity against two representative FR-expression cancer cells. Our observation further supports the previous results which suggest that for a drug to be successfully targeted using the FR, it must be extremely potent against its primary target as the FR has a low delivery efficiency. Published by Elsevier Masson SAS.
• Bright, “Clickable” Porphyrins for the Visualization of Oxygenation under Ambient Light
  作者：Emmanuel Roussakis、Zongxi Li、Nicholas H. Nowell、Alexander J. Nichols、Conor L. Evans

  DOI：10.1002/anie.201506847

  日期：2015.12

  A new group of “clickable” and brightly emissive metalloporphyrins has been developed for the visualization of oxygenation under ambient light with the naked eye. These alkynyl‐terminated compounds permit the rapid and facile synthesis of oxygen‐sensing dendrimers through azide–alkyne click chemistry. With absorption maxima overlapping with the wavelengths of common commercial laser sources, they are

  已经开发了一组新的“可点击的”和发光明亮的金属卟啉，以肉眼可视化环境光下的氧合。这些炔基封端的化合物可通过叠氮化物-炔烃点击化学快速而简便地合成氧敏感树状聚合物。由于吸收最大值与常见的商用激光源的波长重叠，因此它们很容易应用于组织氧合的生物医学成像。描述了一种有效的合成方法，该方法具有稳定的三甲基乙酰基（新戊酰基）保护基，可用于制备。包含新的，点击合成的卟啉树枝状大分子的涂有液体的绷带已用于绘制离体猪皮肤烧伤模型的氧合图。