Benzyl (3S,5S,6R)-3-((((4-bis(tert-butyl)oxacarbonyl)methyl)phenyl)methyl)-6-oxo-5,6-diphenyl-4-morpholinecarboxylate | 261513-63-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: Benzyl (3S,5S,6R)-3-((((4-bis(tert-butyl)oxacarbonyl)methyl)phenyl)methyl)-6-oxo-5,6-diphenyl-4-morpholinecarboxylate
• 英文别名: benzyl (3S,5S,6R)-3-[4-(bis((tert-butyl)oxycarbonyl)methyl)phenylmethyl]-(-)-6-oxo-5,6-diphenyl-4-morpholine-carboxylate；ditert-butyl 2-[4-[[(3S,5S,6R)-2-oxo-5,6-diphenyl-4-phenylmethoxycarbonylmorpholin-3-yl]methyl]phenyl]propanedioate
• CAS: 261513-63-7
• 化学式: C₄₂H₄₅NO₈
• 分子量: 691.821
• InChiKey: DWESUPHVFCSUSE-REAFWAPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.2
• 重原子数：
  51
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  108
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Benzyl (3S,5S,6R)-3-((((4-bis(tert-butyl)oxacarbonyl)methyl)phenyl)methyl)-6-oxo-5,6-diphenyl-4-morpholinecarboxylate 在 钯 水 、 氢气 、 sodium carbonate 、 溶剂黄146 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 为溶剂， 20.0 ℃ 、310.26 kPa 条件下， 反应 24.0h， 生成 N^α-Fmoc-4-(di-tert-butoxycarbonyl-methyl)-L-phenylalanine
  参考文献：
  名称：

  Gao, Yang; Burke Jr., Terrence R., Synlett, 2000, # 1, p. 134 - 136

  摘要：

  DOI：
• 作为产物：
  描述：

  2-(4-Methylphenyl)malonic acid di-tert-butyl ester 在 N-溴代丁二酰亚胺(NBS) 、 lithium hexamethyldisilazane 、 过氧化苯甲酰 作用下， 以 四氢呋喃 、 四氯化碳 、 六甲基磷酰三胺 、 正己烷 为溶剂， 反应 2.0h， 生成 Benzyl (3S,5S,6R)-3-((((4-bis(tert-butyl)oxacarbonyl)methyl)phenyl)methyl)-6-oxo-5,6-diphenyl-4-morpholinecarboxylate
  参考文献：
  名称：

  Gao, Yang; Burke Jr., Terrence R., Synlett, 2000, # 1, p. 134 - 136

  摘要：

  DOI：

文献信息

• Design and Synthesis of 4-(α-Hydroxymalonyl)phenylalanine as a New Phosphotyrosyl Mimetic and Its Use in Growth Factor Receptor Bound 2 Src-Homology 2 (Grb2 SH2) Domain-Binding Peptides
  作者：Sang-Uk Kang、Karen M. Worthy、Lakshman K. Bindu、Manchao Zhang、Dajun Yang、Robert J. Fisher、Terrence R. Burke

  DOI：10.1021/jm050154v

  日期：2005.8.1

  A new phosphotyrosyl mimetic 4-(alpha-hydroxymalonyl)phenylalanine and its incorporation into a Grb2 SH2 domain-binding tripeptide are presented. In whole-cell studies using malonyl ethyl ester prodrug derivatives, it was observed that the 4-(alpha-hydroxymalonyl)phenylalanyl-containing peptide exhibited greater efficacy than the nonhydroxylated 4-(malonyl)phenylalanyl-containing congener in blocking the association of Grb2 with activated erbB-2 tyrosine kinase. These results are consistent with de-esterification and at least partial intracellular decarboxylation.
• Inhibition of Grb2 SH2 Domain Binding by Non-Phosphate-Containing Ligands. 2. 4-(2-Malonyl)phenylalanine as a Potent Phosphotyrosyl Mimetic
  作者：Yang Gao、Juliet Luo、Zhu-Jun Yao、Ribo Guo、Hong Zou、James Kelley、Johannes H. Voigt、Dajun Yang、Terrence R. Burke

  DOI：10.1021/jm9904248

  日期：2000.3.1

  Nonhydrolyzable phosphotyrosyl (pTyr) mimetics serve as important components of many competitive Grb2 SH2 domain inhibitors. To date, the most potent of these inhibitors have relied on phosphonate-based structures to replace the 4-phosphoryl group of the parent pTyr residue. Reported herein is the design and evaluation of a new pTyr mimetic, p-malonylphenylalanine (Pmf), which does not contain phosphorus yet, in Grb2 SH2 domain binding systems, approaches the potency of phosphonate-based pTyr mimetics. When incorporated into high affinity Grb2 SH2 domain-directed platforms, Pmf is 15-20 times more potent than the closely related previously reported pTyr mimetic, O-malonyltyrosine (OMT). Pmf-containing inhibitors show inhibition constants as low as 8 nM in extracellular Grb2 binding assays and in whole cell systems, effective blockade of both endogenous Grb2 binding to cognate erbB-2, and downstream MAP kinase activation. Evidence is provided that use of an N-alpha-oxalyl auxiliary enhances effectiveness of Pmf and other inhibitors in both extracellular and intracellular contexts. As one of the most potent Grb2 SH2 domain-directed pTyr mimetics yet disclosed, Pmf may potentially have utility in the design of new chemotherapeutics for the treatment of various proliferative diseases, including breast cancer.
• Gao, Yang; Burke Jr., Terrence R., Synlett, 2000, # 1, p. 134 - 136
  作者：Gao, Yang、Burke Jr., Terrence R.

  DOI：——

  日期：——