(R)-2-hydroxyphosphinoylmethylpentanedioic acid dibenzyl ester | 496812-78-3

• 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: (R)-2-hydroxyphosphinoylmethylpentanedioic acid dibenzyl ester
• 英文别名: (R)-2-(2-hydroxyphosphinoylmethyl)pentanedioic acid dibenzyl ester；[(2R)-5-oxo-5-phenylmethoxy-2-phenylmethoxycarbonylpentyl]phosphinic acid
• CAS: 496812-78-3
• 化学式: C₂₀H₂₃O₆P
• 分子量: 390.373
• InChiKey: LZLYJQVFORDMDW-SFHVURJKSA-N

物化性质

• 沸点：
  556.5±60.0 °C(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  27
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  95.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (R)-2-hydroxyphosphinoylmethylpentanedioic acid dibenzyl ester 在 sodium periodate 作用下， 以 水 、 乙腈 为溶剂， 反应 3.0h， 以57%的产率得到(R)-2-(phosphonomethyl)pentanedioic acid dibenzyl ester
  参考文献：
  名称：

  Synthesis and biological evaluation of (R)- and (S)-2-(phosphonomethyl)pentanedioic acids as inhibitors of glutamate carboxypeptidase II

  摘要：

  Both enantiomers of 2-(phosphonomethyl)pentanedioic acid (2-PMPA), a potent and selective inhibitor of glutamate carboxypeptidase II (GCP II). were successfully prepared through the resolution of racemic 2-(hydroxyphosphinoylmethyl)pentanedioic acid dibenzyl ester with yohimbine and (S)-alpha-methylbenzylamine. The enantiomeric purity of the resolved phosphinic acid was measured by coupling it to (-)-menthol and analyzing the resulting ester by P-31 NMR. The absolute configuration of the 2-carbon atom in the resolved phosphinic acid was determined by X-ray crystallographic studies. Optically pure 2-PMPA was obtained by oxidation of the resolved phophinic acid to the phosphonic acid followed by catalytic hydrogenolysis. The biological activity of each enantiomer of 2-PMPA will also be described, (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(02)00412-3
• 作为产物：
  描述：

  dibenzyl 2-methylenepentanedioate 在 三甲基氯硅烷 、 ammonium hypophosphite 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 (R)-2-hydroxyphosphinoylmethylpentanedioic acid dibenzyl ester
  参考文献：
  名称：

  Synthesis and biological evaluation of (R)- and (S)-2-(phosphonomethyl)pentanedioic acids as inhibitors of glutamate carboxypeptidase II

  摘要：

  Both enantiomers of 2-(phosphonomethyl)pentanedioic acid (2-PMPA), a potent and selective inhibitor of glutamate carboxypeptidase II (GCP II). were successfully prepared through the resolution of racemic 2-(hydroxyphosphinoylmethyl)pentanedioic acid dibenzyl ester with yohimbine and (S)-alpha-methylbenzylamine. The enantiomeric purity of the resolved phosphinic acid was measured by coupling it to (-)-menthol and analyzing the resulting ester by P-31 NMR. The absolute configuration of the 2-carbon atom in the resolved phosphinic acid was determined by X-ray crystallographic studies. Optically pure 2-PMPA was obtained by oxidation of the resolved phophinic acid to the phosphonic acid followed by catalytic hydrogenolysis. The biological activity of each enantiomer of 2-PMPA will also be described, (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(02)00412-3

文献信息

• Enantiospecificity of Glutamate Carboxypeptidase II Inhibition
  作者：Takashi Tsukamoto、Pavel Majer、Dilrukshi Vitharana、Chiyou Ni、Bunda Hin、Xi-Chun M. Lu、Ajit G. Thomas、Krystyna M. Wozniak、David C. Calvin、Ying Wu、Barbara S. Slusher、David Scarpetti、George W. Bonneville

  DOI：10.1021/jm049258g

  日期：2005.4.1

  edioic acid 3, were synthesized in high optical purities (>97%ee). The two enantiomers of 2 were prepared from previously reported chiral intermediates, (R)- and (S)-2-(hydroxyphosphinoylmethyl)pentanedioic acid benzyl esters 8. The synthesis of (R)- and (S)-3 involves the hydrolysis of (R)- and (S)-3-(2-oxo-tetrahydro-thiopyran-3-yl)propionic acids, (R)- and (S)-11, the corresponding optically pure

  以高光学纯度（> 97％ee）合成了两种代表性的谷氨酸羧肽酶II（GCP II）抑制剂2-（羟基五氟苯基甲基-膦酰基甲基）戊二酸2和2-（3-巯基丙基）戊二酸3。2的两个对映异构体是由先前报道的手性中间体（R）-和（S）-2-（羟基膦酰基甲基）戊二酸苄酯8制备的。（R）-和（S）-3的合成涉及水解（R）-和（S）-3-（2-氧代-四氢-硫吡喃-3-基）丙酸，（R）-和（S）-11，通过手性色谱分离得到的相应的光学纯硫内酯外消旋体11. GCP II抑制试验表明，（S）-2的效力比（R）-2高40倍。相反，两种3的对映体均以几乎相同的效力抑制GCP II。