[[2-(4,8-二甲基壬-3,7-二烯基)-2-甲基-3-(2,6,10-三甲基十一碳-1,5,9-三烯基)环丙基]甲氧基-羟基-磷酰]氧基膦酸 | 29849-75-0

• 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
• 中文名称: [[2-(4,8-二甲基壬-3,7-二烯基)-2-甲基-3-(2,6,10-三甲基十一碳-1,5,9-三烯基)环丙基]甲氧基-羟基-磷酰]氧基膦酸
• 英文名称: (E)-presqualene
• 英文别名: (+/-)-Presqualene diphosphate；[(1S,2S,3S)-2-[(3E)-4,8-dimethylnona-3,7-dienyl]-2-methyl-3-[(1E,5E)-2,6,10-trimethylundeca-1,5,9-trienyl]cyclopropyl]methyl phosphono hydrogen phosphate
• CAS: 29849-75-0
• 化学式: C₃₀H₅₂O₇P₂
• 分子量: 586.686
• InChiKey: ATZKAUGGNMSCCY-VYCBRMPGSA-N

物化性质

• 沸点：
  665.2±63.0 °C(Predicted)
• 密度：
  1.121±0.06 g/cm3(Predicted)
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  39
• 可旋转键数：
  18
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  113
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  法尼基二磷酸-三铵盐 在 dehydrosqualene synthase 作用下， 生成 [[2-(4,8-二甲基壬-3,7-二烯基)-2-甲基-3-(2,6,10-三甲基十一碳-1,5,9-三烯基)环丙基]甲氧基-羟基-磷酰]氧基膦酸
  参考文献：
  名称：

  HIV-1 Integrase Inhibitor-Inspired Antibacterials Targeting Isoprenoid Biosynthesis

  摘要：

  We report the discovery of antibacterial leads, keto- and diketo-acids, targeting two prenyl transferases: undecaprenyl diphosphate synthase (UPPS) and dehydrosqualene synthase (CrtM). The leads were suggested by the observation that keto- and diketo-acids bind to the active site Mg2+/Asp domain in HIV-1 integrase, and similar domains are present in prenyl transferases. We report the X-ray crystallographic structures of one diketo-acid and one keto-acid bound to CrtM, which supports the Mg2+ binding hypothesis, together with the X-ray structure of one diketo-acid bound to UPPS. In all cases, the inhibitors bind to a farnesyl diphosphate substrate-binding site. Compound 45 had cell growth inhibition MIC90 values of similar to 250-500 ng/mL against Staphylococcus aureus, 500 ng/mL against Bacillus anthracis, 4 mu g/mL against Listeria monocytogenes and Enterococcus faecium, and 1 mu g/mL against Streptococcus pyogenes M1 but very little activity against Escherichia coli (DH5 alpha, K12) or human cell lines.

  DOI：

  10.1021/ml300038t

文献信息

• Enantioselective Synthesis of (+)-Presqualene Diphosphate
  作者：Daniel H. Rogers、Eugene C. Yi、C. Dale Poulter

  DOI：10.1021/jo00109a026

  日期：1995.2

  (+)-(1R,2R,3R)-Presqualene diphosphate (PSPP) is an intermediate in the biosynthesis of squalene from farnesyl diphosphate (FPP). The natural 1R,2R,3R enantiomer was synthesized from farnesol in nine steps with greater than or equal to 98% ee. The key step in the synthesis was the stereoselective intramolecular cyclopropanation of farnesyl diazoacetate (5) upon treatment with a chiral rhodium catalyst to give (-)-lactone 6.

  (+)-(1R,2R,3R)-Legalene 二磷酸（PSPP）是法呢烯二磷酸（FPP）生物合成鲨烯过程中的一个中间体。天然的1R,2R,3R 对映异构体通过从法呢醇出发的九步合成路线制得，纯度超过或等于98% ee。合成的关键步骤是法呢基叠氮醋酸酯（5）在手性铑催化剂作用下选择性的分子内环丙烷化，生成(-)-环酯6。
• MODULATION OF PHOSPHOLIPASE D FOR THE TREATMENT OF NEURODEGENERATIVE DISORDERS
  申请人：DiPaolo Gilbert

  公开号：US20120178719A1

  公开（公告）日：2012-07-12

  The present invention relates to methods of treating neurodegenerative diseases comprising administering, to a subject in need of such treatment, one or more agent that inhibits or reduces the action, including the catalytic activity, of an enzyme of the phospholipase D family, such as phospholipase D1 and/or phospholipase D2. The present invention also relates to cell-based assays which may be used to identify agents that inhibit or reduce the activity of enzymes of the phospholipase D family and that may be used in the treatment of neurodegenerative diseases.
• Modulation of Phospholipase D for the Treatment of the Acute and Chronic Effects of Ethanol
  申请人：DiPaolo Gilbert

  公开号：US20120302604A1

  公开（公告）日：2012-11-29

  The present invention relates to methods of decreasing the negative effects of alcohol on behavior as well as inhibiting the toxic effects of alcohol, comprising administering, to a subject, an effective amount of an inhibitor of phospholipase D.
• US9267122B2
  申请人：——

  公开号：US9267122B2

  公开（公告）日：2016-02-23
• HIV-1 Integrase Inhibitor-Inspired Antibacterials Targeting Isoprenoid Biosynthesis
  作者：Yonghui Zhang、Fu-Yang Lin、Kai Li、Wei Zhu、Yi-Liang Liu、Rong Cao、Ran Pang、Eunhae Lee、Jordan Axelson、Mary Hensler、Ke Wang、Katie J. Molohon、Yang Wang、Douglas A. Mitchell、Victor Nizet、Eric Oldfield

  DOI：10.1021/ml300038t

  日期：2012.5.10

  We report the discovery of antibacterial leads, keto- and diketo-acids, targeting two prenyl transferases: undecaprenyl diphosphate synthase (UPPS) and dehydrosqualene synthase (CrtM). The leads were suggested by the observation that keto- and diketo-acids bind to the active site Mg2+/Asp domain in HIV-1 integrase, and similar domains are present in prenyl transferases. We report the X-ray crystallographic structures of one diketo-acid and one keto-acid bound to CrtM, which supports the Mg2+ binding hypothesis, together with the X-ray structure of one diketo-acid bound to UPPS. In all cases, the inhibitors bind to a farnesyl diphosphate substrate-binding site. Compound 45 had cell growth inhibition MIC90 values of similar to 250-500 ng/mL against Staphylococcus aureus, 500 ng/mL against Bacillus anthracis, 4 mu g/mL against Listeria monocytogenes and Enterococcus faecium, and 1 mu g/mL against Streptococcus pyogenes M1 but very little activity against Escherichia coli (DH5 alpha, K12) or human cell lines.