trans-4-hydroxycyclophosphamide | 40277-05-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: trans-4-hydroxycyclophosphamide
• 英文别名: (S)-4-hydroxycyclophosphamide；(R,S)-4-Hydroxy Cyclophosphamide；(4S)-2-[bis(2-chloroethyl)amino]-2-oxo-1,3,2λ5-oxazaphosphinan-4-ol
• CAS: 40277-05-2；61903-29-5；61903-30-8；88852-77-1；88852-78-2
• 化学式: C₇H₁₅Cl₂N₂O₃P
• 分子量: 277.087
• InChiKey: RANONBLIHMVXAJ-CIFJEQONSA-N

物化性质

• 沸点：
  387.1±52.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  61.8
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  trans-4-hydroxycyclophosphamide 在 水 作用下， 以 甲醇 为溶剂， 生成 cis-4-hydroxycyclophosphamide
  参考文献：
  名称：

  The mechanism of activation of 4-hydroxycyclophosphamide

  摘要：

  4-Hydroxycyclophosphamide (2/3) of unknown stereochemistry is the initial metabolite formed after administration of cyclophosphamide (1). Ultimate conversion to the cytotoxic metabolite phosphoramide mustard (6) is initiated by ring opening of 4-hydroxycyclophosphamide to produce aldophosphamide (4). The ring-opening reaction and subsequent equilibration of 2-4 are subject to general-acid catalysis, and the equilibrium composition is independent of buffer structure and pH. In contrast, formation of 6 from 4 proceeds by general-base-catalyzed beta-elimination. trans-4-Hydroxycyclophosphamide undergoes ring opening ca. 4 times faster than the cis isomer, and cyclization of 4 favors the trans isomer by a factor of ca. 3 over the cis isomer. The rapid equilibration of 2-5 and the absence of elimination to give 6 at pH approximately 5 provides a convenient method to prepare a stable equilibrium mixture of activated cyclophosphamide metabolites suitable for in vitro use.

  DOI：

  10.1021/jm00385a029
• 作为产物：
  描述：

  aldophosphamide hydrate 在 水 作用下， 以 甲醇 为溶剂， 生成 trans-4-hydroxycyclophosphamide
  参考文献：
  名称：

  The mechanism of activation of 4-hydroxycyclophosphamide

  摘要：

  4-Hydroxycyclophosphamide (2/3) of unknown stereochemistry is the initial metabolite formed after administration of cyclophosphamide (1). Ultimate conversion to the cytotoxic metabolite phosphoramide mustard (6) is initiated by ring opening of 4-hydroxycyclophosphamide to produce aldophosphamide (4). The ring-opening reaction and subsequent equilibration of 2-4 are subject to general-acid catalysis, and the equilibrium composition is independent of buffer structure and pH. In contrast, formation of 6 from 4 proceeds by general-base-catalyzed beta-elimination. trans-4-Hydroxycyclophosphamide undergoes ring opening ca. 4 times faster than the cis isomer, and cyclization of 4 favors the trans isomer by a factor of ca. 3 over the cis isomer. The rapid equilibration of 2-5 and the absence of elimination to give 6 at pH approximately 5 provides a convenient method to prepare a stable equilibrium mixture of activated cyclophosphamide metabolites suitable for in vitro use.

  DOI：

  10.1021/jm00385a029

文献信息

• COMPOUNDS AND COMPOSITIONS FOR USE AS ALKYLATING AGENT SENSORS AND METHODS OF USE THEREOF
  申请人：The University of British Columbia

  公开号：US20160131641A1

  公开（公告）日：2016-05-12

  This invention provides compound having a structure of Formula I: Uses of such compounds and compositions comprising the compounds as alkylating agent sensors.

  该发明提供了具有I式结构的化合物：这些化合物的用途和包含这些化合物的组合物作为烷基化剂传感器。
• US9638690B2
  申请人：——

  公开号：US9638690B2

  公开（公告）日：2017-05-02
• The mechanism of activation of 4-hydroxycyclophosphamide
  作者：Richard F. Borch、Jo Ann Millard

  DOI：10.1021/jm00385a029

  日期：1987.2

  4-Hydroxycyclophosphamide (2/3) of unknown stereochemistry is the initial metabolite formed after administration of cyclophosphamide (1). Ultimate conversion to the cytotoxic metabolite phosphoramide mustard (6) is initiated by ring opening of 4-hydroxycyclophosphamide to produce aldophosphamide (4). The ring-opening reaction and subsequent equilibration of 2-4 are subject to general-acid catalysis, and the equilibrium composition is independent of buffer structure and pH. In contrast, formation of 6 from 4 proceeds by general-base-catalyzed beta-elimination. trans-4-Hydroxycyclophosphamide undergoes ring opening ca. 4 times faster than the cis isomer, and cyclization of 4 favors the trans isomer by a factor of ca. 3 over the cis isomer. The rapid equilibration of 2-5 and the absence of elimination to give 6 at pH approximately 5 provides a convenient method to prepare a stable equilibrium mixture of activated cyclophosphamide metabolites suitable for in vitro use.