(2S,3S)-3-(4-{bis[(tert-butyl)oxycarbonyl]methyl}-phenyl)-2-{[(tert-butyl)oxycarbonyl]methyl}-pent-4-enoic acid | 641638-41-7

• 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: (2S,3S)-3-(4-{bis[(tert-butyl)oxycarbonyl]methyl}-phenyl)-2-{[(tert-butyl)oxycarbonyl]methyl}-pent-4-enoic acid
• CAS: 641638-41-7
• 化学式: C₂₈H₄₀O₈
• 分子量: 504.621
• InChiKey: AZHZMNUOLTWDAN-UXHICEINSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.16
• 重原子数：
  36.0
• 可旋转键数：
  9.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  116.2
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (2S,3S)-3-(4-{bis[(tert-butyl)oxycarbonyl]methyl}-phenyl)-2-{[(tert-butyl)oxycarbonyl]methyl}-pent-4-enoic acid 在 三乙基硅烷 、 N-羟基-7-氮杂苯并三氮唑 、 [((PCy₃)(Im(2,4,6-trimethylphenyl)2)Ru=CHPh)] 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 66.5h， 生成 2-{4-[(9S,10S,14S,18S)-7,16,19-triaza-18-(carbamoylmethyl)-9-carboxymethyl-14-(naphthylmethyl)-8,17,20-trioxospiro[5,14]icos-11-en-10-yl]phenyl}propanedioic acid
  参考文献：
  名称：

  Macrocyclization in the Design of Non-Phosphorus-Containing Grb2 SH2 Domain-Binding Ligands

  摘要：

  Macrocyclization from the phosphotyrosyl. (pTyr) mimetic's beta-position has previously been shown to enhance Grb2 SH2 domain-binding affinity of phosphonate-based analogues. The current study examined the effects of such macrocyclization using a dicarboxymethyl-based pTyr mimetic. In extracellular assays affinity was enhanced approximately 5-fold relative to an open-chain congener. Enhancement was also observed in whole-cell assays examining blockade of Grb2 binding to the erbB-2 protein-tyrosine kinase.

  DOI：

  10.1021/jm030510e
• 作为产物：
  描述：

  2-{4-[(1E)-3-((4S)-2-oxo-4-phenyl-(1,3-oxazolidin-3-yl))-3-oxoprop-1-enyl]phenyl}propane-1,3-dioic acid bis(1,1-dimethylethyl) ester 在 lithium hydroxide 、 双氧水 、 sodium hexamethyldisilazane 、 苯硫酚铜(I) 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 10.83h， 生成 (2S,3S)-3-(4-{bis[(tert-butyl)oxycarbonyl]methyl}-phenyl)-2-{[(tert-butyl)oxycarbonyl]methyl}-pent-4-enoic acid
  参考文献：
  名称：

  Macrocyclization in the Design of Non-Phosphorus-Containing Grb2 SH2 Domain-Binding Ligands

  摘要：

  Macrocyclization from the phosphotyrosyl. (pTyr) mimetic's beta-position has previously been shown to enhance Grb2 SH2 domain-binding affinity of phosphonate-based analogues. The current study examined the effects of such macrocyclization using a dicarboxymethyl-based pTyr mimetic. In extracellular assays affinity was enhanced approximately 5-fold relative to an open-chain congener. Enhancement was also observed in whole-cell assays examining blockade of Grb2 binding to the erbB-2 protein-tyrosine kinase.

  DOI：

  10.1021/jm030510e

文献信息

• Examination of Phosphoryl-Mimicking Functionalities within a Macrocyclic Grb2 SH2 Domain-Binding Platform
  作者：Sang-Uk Kang、Zhen-Dan Shi、Karen M. Worthy、Lakshman K. Bindu、Pathirage G. Dharmawardana、Sarah J. Choyke、Donald P. Bottaro、Robert J. Fisher、Terrence R. Burke

  DOI：10.1021/jm050059m

  日期：2005.6.1

  Reported herein are the design, synthesis, and Grb2 SH2 domain-binding affinities of several phosphoryl-mimicking groups displayed within the context of a conformationally constrained macrocyclic platform. With use of surface plasmon resonance techniques, single-digit nanomolar affinities were exhibited by phosphonic acid and malonyl-containing diacidic phosphoryl mimetics (for 4h and 4g, K-D = 1.47 and 3.62 nM, respectively). Analogues containing monoacidic phosphoryl mimetics provided affinities of K-D = 16-67 nM. Neutral phosphoryl-mimicking groups did not show appreciable binding.