(E)-2-[2-methyl-4-(tetrahydropyran-2-yloxy)but-2-enyl]isoindole-1,3-dione | 196799-86-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: (E)-2-[2-methyl-4-(tetrahydropyran-2-yloxy)but-2-enyl]isoindole-1,3-dione
• 英文别名: (E)-1-[(tetrahydro-2H-pyran-2-yl)oxy]-3-methyl-4-N-phthalamido-2-butene；2-[(E)-2-methyl-4-(oxan-2-yloxy)but-2-enyl]isoindole-1,3-dione
• CAS: 196799-86-7
• 化学式: C₁₈H₂₁NO₄
• 分子量: 315.369
• InChiKey: UGARBAFKFVBKOA-UKTHLTGXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-2-[2-methyl-4-(tetrahydropyran-2-yloxy)but-2-enyl]isoindole-1,3-dione 在 磷酸 、 TEA 、 4-甲基苯磺酸吡啶 、 一水合肼 、 三氯乙腈 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 26.0h， 生成 {[(2E)-4-[(3-benzoylphenyl)formamido]-3-methylbut-2-en-1-yl phosphonato]oxy}phosphonate
  参考文献：
  名称：

  Synthesis and evaluation of benzophenone-based photoaffinity labeling analogs of prenyl pyrophosphates containing stable amide linkages

  摘要：

  The syntheses of two photoactive prenyl pyrophosphate analogs (1a and 1b) that incorporate stable amide-linked benzophenones are described. Compound 1a contains a single isoprene (C-5) unit between the pyrophosphate and benzophenone functionalities while 1b contains a geranyl (C-10) moiety. Compounds 1a and 1b are competitive inhibitors of yeast farnesyl protein transferase with respect to farnesyl pyrophosphate and have K-I values of 6000 nM and 700 nM. Upon irradiation, [P-32]-1b preferentially labels the beta-subunits of yeast farnesyl protein transferase and human geranylgeranyl protein transferase. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00373-9
• 作为产物：
  描述：

  异戊烯醇 在 叔丁基过氧化氢 、 4-甲基苯磺酸吡啶 、 硒脲酸 、 三苯基膦 、 水杨酸 、 偶氮二甲酸二乙酯 作用下， 以 二氯甲烷 为溶剂， 生成 (E)-2-[2-methyl-4-(tetrahydropyran-2-yloxy)but-2-enyl]isoindole-1,3-dione
  参考文献：
  名称：

  Synthesis and evaluation of benzophenone-based photoaffinity labeling analogs of prenyl pyrophosphates containing stable amide linkages

  摘要：

  The syntheses of two photoactive prenyl pyrophosphate analogs (1a and 1b) that incorporate stable amide-linked benzophenones are described. Compound 1a contains a single isoprene (C-5) unit between the pyrophosphate and benzophenone functionalities while 1b contains a geranyl (C-10) moiety. Compounds 1a and 1b are competitive inhibitors of yeast farnesyl protein transferase with respect to farnesyl pyrophosphate and have K-I values of 6000 nM and 700 nM. Upon irradiation, [P-32]-1b preferentially labels the beta-subunits of yeast farnesyl protein transferase and human geranylgeranyl protein transferase. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00373-9

文献信息

• Inhibition of IspH, a [4Fe–4S]²⁺ Enzyme Involved in the Biosynthesis of Isoprenoids via the Methylerythritol Phosphate Pathway
  作者：Karnjapan Janthawornpong、Sergiy Krasutsky、Philippe Chaignon、Michel Rohmer、C. Dale Poulter、Myriam Seemann

  DOI：10.1021/ja309557s

  日期：2013.2.6

  The MEP pathway, which is absent in animals but present in most pathogenic bacteria, in the parasite responsible for malaria and in plant plastids, is a target for the development of antimicrobial drugs. IspH, an oxygen-sensitive [4Fe-4S] enzyme, catalyzes the last step of this pathway and converts (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate (HMBPP) into the two isoprenoid precursors: isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). A crucial step in the mechanism of this enzyme is the binding of the C4 hydroxyl of HMBPP to the unique fourth iron site in the [4Fe-4S](2+) moiety. Here, we report the synthesis and the kinetic investigations of two new extremely potent inhibitors of E. coli IspH where the OH group of HMBPP is replaced by an amino and a thiol group. (E)-4-Mercapto-3-methylbut-2-en-1-yl diphosphate is a reversible tight-binding inhibitor of IspH with K-i = 20 +/- 2, nM. A detailed kinetic analysis revealed that (E)-4-amino-3-methylbut-2-en-1-yl diphosphate is a reversible slow-binding inhibitor of IspH with K-i = 54 +/- 19 nM. The slow binding behavior of this inhibitor is best described by a one-step mechanism with the slow step consisting of the formation of the enzyme-inhibitor (EI) complex.
• 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.
• Synthesis and evaluation of benzophenone-based photoaffinity labeling analogs of prenyl pyrophosphates containing stable amide linkages
  作者：Tammy C. Turek、Igor Gaon、Dave Gamache、Mark D. Distefano

  DOI：10.1016/s0960-894x(97)00373-9

  日期：1997.8

  The syntheses of two photoactive prenyl pyrophosphate analogs (1a and 1b) that incorporate stable amide-linked benzophenones are described. Compound 1a contains a single isoprene (C-5) unit between the pyrophosphate and benzophenone functionalities while 1b contains a geranyl (C-10) moiety. Compounds 1a and 1b are competitive inhibitors of yeast farnesyl protein transferase with respect to farnesyl pyrophosphate and have K-I values of 6000 nM and 700 nM. Upon irradiation, [P-32]-1b preferentially labels the beta-subunits of yeast farnesyl protein transferase and human geranylgeranyl protein transferase. (C) 1997 Elsevier Science Ltd.