(E)-4-(3'-benzoylbenzyloxy)-3-methyl-2-buten-1-ol | 344558-14-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (E)-4-(3'-benzoylbenzyloxy)-3-methyl-2-buten-1-ol
• 英文别名: [3-[[(E)-4-hydroxy-2-methylbut-2-enoxy]methyl]phenyl]-phenylmethanone
• CAS: 344558-14-1
• 化学式: C₁₉H₂₀O₃
• 分子量: 296.366
• InChiKey: PJEKHCNVZKDTEL-XNTDXEJSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-4-(3'-benzoylbenzyloxy)-3-methyl-2-buten-1-ol 在 四溴化碳 、 zinc diacetate 、 三苯基膦 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 正丁醇 为溶剂， 反应 4.0h， 生成 (S)-2-[(S)-2-((S)-2-{(R)-3-[(E)-4-(3-Benzoyl-benzyloxy)-3-methyl-but-2-enylsulfanyl]-2-[2-(5-dimethylamino-naphthalene-1-sulfonylamino)-acetylamino]-propionylamino}-3-methyl-butyrylamino)-3-methyl-pentanoylamino]-propionic acid
  参考文献：
  名称：

  Synthesis of Farnesyl Diphosphate Analogues Containing Ether-Linked Photoactive Benzophenones and Their Application in Studies of Protein Prenyltransferases

  摘要：

  Protein prenylation is a posttranslational lipid modification in which C-15 and C-20 isoprenoid units are linked to specific protein-derived cysteine residues through a thioether linkage. This process is catalyzed by a class of enzymes called prenyltransferases that are being intensively studied due to the finding that Pas protein is farnesylated coupled with the observation that mutant forms of Pas are implicated in a variety of human cancers. Inhibition of this posttranslational modification may serve as a possible cancer chemotherapy. Here, the syntheses of two new farnesyl diphosphate (FPP) analogues containing photoactive benzophenone groups are described. Each of these compounds was prepared in six steps from dimethylallyl alcohol. Substrate studies, inhibition kinetics, photoinactivation studies, and photolabeling experiments are also included; these experiments were performed with a number of protein prenyltransferases from different sources. A X-ray crystal structure of one of these analogues bound to rat farnesyltransferase illustrates that they are good substrate mimics. Of particular importance, these new analogues can be enzymatically incorporated into Pas-based peptide substrates allowing the preparation of molecules with photoactive isoprenoids that may serve as valuable probes for the study of prenylation function. Photoaffinity labeling of human protein geranylgeranyltransferase with P-32-labeled forms of these analogues suggests that the C-10 locus of bound geranylgeranyl diphosphate (GGPP) is in close proximity to residues from the beta -subunit of this enzyme. These results,clearly demonstrate the utility of these compounds as photoaffinity labeling analogues for the study of a variety of protein prenyltransferases and other enzymes that employ FPP or GGPP as their substrates.

  DOI：

  10.1021/jo991130x
• 作为产物：
  描述：

  1-[(tetrahydro-2H-pyran-2-yl)oxy]-3-methyl-2-butene 在 叔丁基过氧化氢 、 4-甲基苯磺酸吡啶 、 硒脲酸 、 sodium hydride 、 水杨酸 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 19.0h， 生成 (E)-4-(3'-benzoylbenzyloxy)-3-methyl-2-buten-1-ol
  参考文献：
  名称：

  Synthesis of Farnesyl Diphosphate Analogues Containing Ether-Linked Photoactive Benzophenones and Their Application in Studies of Protein Prenyltransferases

  摘要：

  Protein prenylation is a posttranslational lipid modification in which C-15 and C-20 isoprenoid units are linked to specific protein-derived cysteine residues through a thioether linkage. This process is catalyzed by a class of enzymes called prenyltransferases that are being intensively studied due to the finding that Pas protein is farnesylated coupled with the observation that mutant forms of Pas are implicated in a variety of human cancers. Inhibition of this posttranslational modification may serve as a possible cancer chemotherapy. Here, the syntheses of two new farnesyl diphosphate (FPP) analogues containing photoactive benzophenone groups are described. Each of these compounds was prepared in six steps from dimethylallyl alcohol. Substrate studies, inhibition kinetics, photoinactivation studies, and photolabeling experiments are also included; these experiments were performed with a number of protein prenyltransferases from different sources. A X-ray crystal structure of one of these analogues bound to rat farnesyltransferase illustrates that they are good substrate mimics. Of particular importance, these new analogues can be enzymatically incorporated into Pas-based peptide substrates allowing the preparation of molecules with photoactive isoprenoids that may serve as valuable probes for the study of prenylation function. Photoaffinity labeling of human protein geranylgeranyltransferase with P-32-labeled forms of these analogues suggests that the C-10 locus of bound geranylgeranyl diphosphate (GGPP) is in close proximity to residues from the beta -subunit of this enzyme. These results,clearly demonstrate the utility of these compounds as photoaffinity labeling analogues for the study of a variety of protein prenyltransferases and other enzymes that employ FPP or GGPP as their substrates.

  DOI：

  10.1021/jo991130x

文献信息

• Synthesis of Farnesyl Diphosphate Analogues Containing Ether-Linked Photoactive Benzophenones and Their Application in Studies of Protein Prenyltransferases
  作者：Tammy C. Turek、Igor Gaon、Mark D. Distefano、Corey L. Strickland

  DOI：10.1021/jo991130x

  日期：2001.5.1

  Protein prenylation is a posttranslational lipid modification in which C-15 and C-20 isoprenoid units are linked to specific protein-derived cysteine residues through a thioether linkage. This process is catalyzed by a class of enzymes called prenyltransferases that are being intensively studied due to the finding that Pas protein is farnesylated coupled with the observation that mutant forms of Pas are implicated in a variety of human cancers. Inhibition of this posttranslational modification may serve as a possible cancer chemotherapy. Here, the syntheses of two new farnesyl diphosphate (FPP) analogues containing photoactive benzophenone groups are described. Each of these compounds was prepared in six steps from dimethylallyl alcohol. Substrate studies, inhibition kinetics, photoinactivation studies, and photolabeling experiments are also included; these experiments were performed with a number of protein prenyltransferases from different sources. A X-ray crystal structure of one of these analogues bound to rat farnesyltransferase illustrates that they are good substrate mimics. Of particular importance, these new analogues can be enzymatically incorporated into Pas-based peptide substrates allowing the preparation of molecules with photoactive isoprenoids that may serve as valuable probes for the study of prenylation function. Photoaffinity labeling of human protein geranylgeranyltransferase with P-32-labeled forms of these analogues suggests that the C-10 locus of bound geranylgeranyl diphosphate (GGPP) is in close proximity to residues from the beta -subunit of this enzyme. These results,clearly demonstrate the utility of these compounds as photoaffinity labeling analogues for the study of a variety of protein prenyltransferases and other enzymes that employ FPP or GGPP as their substrates.