tert-butyl N-[(2S)-6-[[2-[diethoxy(oxido)phosphaniumyl]acetyl]amino]-1-[[(2S)-1-hydroxy-3-methylbutan-2-yl]amino]-1-oxohexan-2-yl]carbamate | 1227203-75-9

• 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: tert-butyl N-[(2S)-6-[[2-[diethoxy(oxido)phosphaniumyl]acetyl]amino]-1-[[(2S)-1-hydroxy-3-methylbutan-2-yl]amino]-1-oxohexan-2-yl]carbamate
• CAS: 1227203-75-9
• 化学式: C₂₂H₄₄N₃O₈P
• 分子量: 509.58
• InChiKey: MLSZJYPGHWWNJW-ZWKOTPCHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  34
• 可旋转键数：
  18
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  158
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[(2S)-6-[[2-[diethoxy(oxido)phosphaniumyl]acetyl]amino]-1-[[(2S)-1-hydroxy-3-methylbutan-2-yl]amino]-1-oxohexan-2-yl]carbamate 在 四甲基乙二胺 、 氢溴酸 、 zinc trifluoromethanesulfonate 、 戴斯-马丁氧化剂 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 56.25h， 生成 (2S,3S)-2-(3-dodecylureido)-N-((5S,8S,E)-5-isopropyl-2,7-dioxo-1,6-diazacyclododec-3-en-8-yl)-3-methylpentanamide
  参考文献：
  名称：

  Syntheses and cytotoxicity of syringolin B-based proteasome inhibitors

  摘要：

  The concise and modular total synthesis of the bacterial natural product and irreversible proteasome inhibitor syringolin B has been achieved. This synthesis has enabled the ready preparation of three diverse, structurally modified syringolin derivatives. The actions of these compounds in inhibiting the proliferation of neuroblastoma cell lines was evaluated, and significant enhancements in potency compared to the natural product were realized. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2011.09.048
• 作为产物：
  描述：

  N-alpha-叔丁氧羰基-L-赖氨酸 在 N-羟基丁二酰亚胺 、 sodium carbonate 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 16.5h， 生成 tert-butyl N-[(2S)-6-[[2-[diethoxy(oxido)phosphaniumyl]acetyl]amino]-1-[[(2S)-1-hydroxy-3-methylbutan-2-yl]amino]-1-oxohexan-2-yl]carbamate
  参考文献：
  名称：

  Syntheses and cytotoxicity of syringolin B-based proteasome inhibitors

  摘要：

  The concise and modular total synthesis of the bacterial natural product and irreversible proteasome inhibitor syringolin B has been achieved. This synthesis has enabled the ready preparation of three diverse, structurally modified syringolin derivatives. The actions of these compounds in inhibiting the proliferation of neuroblastoma cell lines was evaluated, and significant enhancements in potency compared to the natural product were realized. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2011.09.048

文献信息

• Total Synthesis of Syringolin A and B
  作者：Michael C. Pirrung、Goutam Biswas、Tannya R. Ibarra-Rivera

  DOI：10.1021/ol100761z

  日期：2010.5.21

  Total syntheses of two recently discovered proteasome inhibitors, syringolin A and B, are reported. The key to our approach was creation of the α,β-unsaturated 12-membered lactam via intramolecular Horner−Wadsworth−Emmons reaction. Such reactions have been broadly used to prepared macrolactones, but this work presents a rarer example of its application to macrolactams. The final steps involved attachment

  据报道，两种最近发现的蛋白酶体抑制剂丁香脂素A和丁香酚B的总合成。我们方法的关键是通过分子内Horner-Wadsworth-Emmons反应生成α，β-不饱和12元内酰胺。这种反应已被广泛用于制备大内酯，但是这项工作为大内酰胺提供了一个罕见的例子。最终步骤包括使用肽偶联方法，包括基于未保护的缬氨酸N-羧酸酐的方法连接双（戊烯基）脲侧链。通过交叉复分解产生了丁香环素A的另外的烯烃。
• Syntheses and cytotoxicity of syringolin B-based proteasome inhibitors
  作者：Tannya R. Ibarra-Rivera、John Opoku-Ansah、Sudhakar Ambadi、André S. Bachmann、Michael C. Pirrung

  DOI：10.1016/j.tet.2011.09.048

  日期：2011.12

  The concise and modular total synthesis of the bacterial natural product and irreversible proteasome inhibitor syringolin B has been achieved. This synthesis has enabled the ready preparation of three diverse, structurally modified syringolin derivatives. The actions of these compounds in inhibiting the proliferation of neuroblastoma cell lines was evaluated, and significant enhancements in potency compared to the natural product were realized. (C) 2011 Elsevier Ltd. All rights reserved.