rac-trans-4-hydroperoxyifosfamide | 39800-28-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧氮杂膦
• 英文名称: rac-trans-4-hydroperoxyifosfamide
• 英文别名: cis-4-hydroperoxyifosfamide；3-(2-chloro-ethyl)-2c-(2-chloro-ethylamino)-2t-oxo-2λ⁵-[1,3,2]oxazaphosphinan-4r-yl hydroperoxide；(2S,4S)-N,3-bis(2-chloroethyl)-4-hydroperoxy-2-oxo-1,3,2lambda5-oxazaphosphinan-2-amine；(2S,4S)-N,3-bis(2-chloroethyl)-4-hydroperoxy-2-oxo-1,3,2λ5-oxazaphosphinan-2-amine
• CAS: 39800-28-7；59884-18-3；64858-36-2
• 化学式: C₇H₁₅Cl₂N₂O₄P
• 分子量: 293.087
• InChiKey: YGZIWEZFFBPCLN-GYKQLYQFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  71
• 氢给体数：
  2
• 氢受体数：
  6

制备方法与用途

过氧化氢一磷酰胺是一种能够穿透血脑屏障(BBB)的抗癌药物。

反应信息

• 作为反应物：
  描述：

  rac-trans-4-hydroperoxyifosfamide 在 sodium carbonate 作用下， 以 氯仿 为溶剂， 生成 (2-chloro-ethyl)-(6-oxo-(9ar)-tetrahydro-6λ⁵-[1,2,4]dioxazino[4,3-c][1,3,2]oxazaphosphinin-6t-yl)-amine
  参考文献：
  名称：

  4-氢过氧异磷酰胺（NSC-227114）及其相关化合物的合成，立体化学和抗肿瘤活性。

  摘要：

  4-羟基过氧化异磷酰胺及其类似物通过O-(3-丁烯基)-N,N'-双(2-氯乙基)磷酸二酰胺及相关O-(3-丁烯基)磷酰胺的臭氧化反应简单合成。4-羟基过氧化异磷酰胺在酸性催化下发生异构化，其磷构型反转生成2-表-4-羟基过氧化异磷酰胺。两种异构体均能通过与亲核试剂及酸反应生成C4取代的异磷酰胺衍生物。对这些异构体及其某些类似物进行了L1210抗白血病活性测试，结果显示，异磷酰胺的C4羟基过氧化改性显著增强了其活性，且磷原子上烷基化功能的立体构型反转同样有效促进了其抗肿瘤作用，作为异磷酰胺的替代激活形式。

  DOI：

  10.1248/cpb.25.1877
• 作为产物：
  描述：

  O-(but-3-enyl) N,N'-bis(2-chloroethyl)phosphorodiamidate 在 臭氧 作用下， 以25%的产率得到rac-trans-4-hydroperoxyifosfamide
  参考文献：
  名称：

  Phosphorus-31 NMR studies of the kinetics of bisalkylation by isophosphoramide mustard: comparisons with phosphoramide mustard

  摘要：

  31P nuclear magnetic resonance spectroscopy was used to measure the pKa (4.28 +/- 0.2) of isophosphoramide mustard (IPM) at 20 degrees C and to study the kinetics and products of the decomposition of IPM at a solution pH value of ca. 7.4 and at temperatures between 20 and 47 degrees C in the presence of nucleophilic trapping agents. At 37 degrees C, the half-life for the first alkylation was ca. 77 min and ca. 171 min for the second alkylation; these data may be compared with those for phosphoramide mustard (Engle, T.W.; Zon, G.; Egan, W.J. Med. Chem. 1982, 25, 1347), wherein the half-lives for the first and second alkylations are approximately the same (18 min). The rate of fragmentation of aldoifosfamide to IPM and acrolein was also studied by NMR spectroscopy (pH 7.0; 37 degrees C; 0.07 M phosphate); under the noted conditions, the half-life of aldoifosfamide was found to be ca. 60 min.

  DOI：

  10.1021/jm00128a018

文献信息

• Synthesis and antitumour activity of stereoisomers of 4-hydroperoxy derivatives of ifosfamide and its bromo analogue
  作者：Konrad Misiura、Daria Szymanowicz、Halina Kusnierczyk、Joanna Wietrzyk、Adam Opolski

  DOI：10.1016/s0014-827x(02)01202-8

  日期：2002.4

  Racemic mixtures and laevorotatory enantiomers of cis- and trans-4-hydroperoxyifosfamide and 4-hydroperoxybromofosfamide possess high antitumour activity both in vitro and in vivo. However, no major differences in biological activity were observed among these stereoisomers. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved.
• Takamizawa,A. et al., Heterocycles, 1977, vol. 7, p. 1091 - 1130
  作者：Takamizawa,A. et al.

  DOI：——

  日期：——
• Synthesis, stereochemistry and antitumor activity of 4-hydroperoxyisophosphamide (NSC-227114) and related compounds.
  作者：AKIRA TAKAMIZAWA、SAICHI MATSUMOTO、TSUYOSHI IWATA、ITSUO MAKINO

  DOI：10.1248/cpb.25.1877

  日期：——

  4-Hydroperoxyisophosphamide and its analogues were simply synthesized by ozonolysis reactions of O-(3-butenyl)-N, N'-bis (2-chloroethyl) phosphorodiamidate and related O-(3-butenyl) phosphoramidates. An acid-catalyzed isomerization of 4-hydroperoxyisophosphamide proceeded with inversion of its phosphorus configuration giving 2-epi-4-hydroperoxyisophosphamide. Both isomers readily afforded C4-substituted isophosphamide derivatives by reactions with nucleophilic agents and acid. L1210 antileukemic activities were tested for the isomers and some analogues revealing that the C4-hydroperoxylation of isophosphamide resulted in a marked enhancement of its activity and that the inverted stereochemistry of an alkylating functionality at the phosphorus atom is also effective in promoting the antitumor action as an alternative activated species of isophosphamide.

  4-羟基过氧化异磷酰胺及其类似物通过O-(3-丁烯基)-N,N'-双(2-氯乙基)磷酸二酰胺及相关O-(3-丁烯基)磷酰胺的臭氧化反应简单合成。4-羟基过氧化异磷酰胺在酸性催化下发生异构化，其磷构型反转生成2-表-4-羟基过氧化异磷酰胺。两种异构体均能通过与亲核试剂及酸反应生成C4取代的异磷酰胺衍生物。对这些异构体及其某些类似物进行了L1210抗白血病活性测试，结果显示，异磷酰胺的C4羟基过氧化改性显著增强了其活性，且磷原子上烷基化功能的立体构型反转同样有效促进了其抗肿瘤作用，作为异磷酰胺的替代激活形式。
• Phosphorus-31 NMR studies of the kinetics of bisalkylation by isophosphoramide mustard: comparisons with phosphoramide mustard
  作者：Jila H. Boal、Margaret Williamson、Victoria L. Boyd、Susan M. Ludeman、William Egan

  DOI：10.1021/jm00128a018

  日期：1989.8

  31P nuclear magnetic resonance spectroscopy was used to measure the pKa (4.28 +/- 0.2) of isophosphoramide mustard (IPM) at 20 degrees C and to study the kinetics and products of the decomposition of IPM at a solution pH value of ca. 7.4 and at temperatures between 20 and 47 degrees C in the presence of nucleophilic trapping agents. At 37 degrees C, the half-life for the first alkylation was ca. 77 min and ca. 171 min for the second alkylation; these data may be compared with those for phosphoramide mustard (Engle, T.W.; Zon, G.; Egan, W.J. Med. Chem. 1982, 25, 1347), wherein the half-lives for the first and second alkylations are approximately the same (18 min). The rate of fragmentation of aldoifosfamide to IPM and acrolein was also studied by NMR spectroscopy (pH 7.0; 37 degrees C; 0.07 M phosphate); under the noted conditions, the half-life of aldoifosfamide was found to be ca. 60 min.