培磷酰胺 | 39800-16-3

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 培磷酰胺
• 中文别名: 4-过氧羟基环磷酰胺
• 英文名称: 4-hydroperoxycyclophosphamide
• 英文别名: 4-HC；4-HPC；Perfosphamide；N,N-bis(2-chloroethyl)-4-hydroperoxy-2-oxo-1,3,2λ5-oxazaphosphinan-2-amine
• CAS: 39800-16-3
• 化学式: C₇H₁₅Cl₂N₂O₄P
• 分子量: 293.087
• InChiKey: VPAWVRUHMJVRHU-UHFFFAOYSA-N

物化性质

• 熔点：
  100-103°C
• 沸点：
  419.9±55.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于丙酮（少量）、氯仿（少量）、甲醇（少量）、DCM

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

安全信息

• 储存条件：
  -20°C，密闭保存，置于干燥处

SDS

Name:	4-Hydroxyperoxycyclophophamide Material Safety Data Sheet
Synonym:	None Known
CAS:	39800-16-3

Section 1 - Chemical Product MSDS Name:4-Hydroxyperoxycyclophophamide Material Safety Data Sheet
Synonym:None Known

---

Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
39800-16-3	4-Hydroxyperoxycyclophophamide	ca. 100	unlisted

Hazard Symbols: None Listed.
Risk Phrases: None Listed.

---

Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
The toxicological properties of this material have not been fully investigated.
Potential Health Effects
Eye:
May cause eye irritation.
Skin:
May cause skin irritation. May be harmful if absorbed through the skin.
Ingestion:
May cause irritation of the digestive tract. The toxicological properties of this substance have not been fully investigated. May be harmful if swallowed.
Inhalation:
May cause respiratory tract irritation. The toxicological properties of this substance have not been fully investigated. May be harmful if inhaled.
Chronic:
No information found.

---

Section 4 - FIRST AID MEASURES
Eyes: In case of contact, immediately flush eyes with plenty of water for at least 15 minutes. Get medical aid.
Skin:
In case of contact, flush skin with plenty of water. Remove contaminated clothing and shoes. Get medical aid if irritation develops and persists. Wash clothing before reuse.
Ingestion:
If swallowed, do not induce vomiting unless directed to do so by medical personnel. Never give anything by mouth to an unconscious person. Get medical aid.
Inhalation:
If inhaled, remove to fresh air. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical aid.
Notes to Physician:
Treat symptomatically and supportively.

---

Section 5 - FIRE FIGHTING MEASURES
General Information:
As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear. During a fire, irritating and highly toxic gases may be generated by thermal decomposition or combustion.
Extinguishing Media:
Use water spray, dry chemical, carbon dioxide, or appropriate foam.

---

Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Clean up spills immediately, observing precautions in the Protective Equipment section. Sweep up or absorb material, then place into a suitable clean, dry, closed container for disposal. Avoid generating dusty conditions. Provide ventilation.

---

Section 7 - HANDLING and STORAGE
Handling:
Wash thoroughly after handling. Use with adequate ventilation.
Minimize dust generation and accumulation. Avoid contact with eyes, skin, and clothing. Keep container tightly closed. Avoid ingestion and inhalation.
Storage:
Store in a tightly closed container. Store in a cool, dry, well-ventilated area away from incompatible substances.

---

Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Facilities storing or utilizing this material should be equipped with an eyewash facility and a safety shower. Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 39800-16-3: Personal Protective Equipment Eyes: Wear appropriate protective eyeglasses or chemical safety goggles as described by OSHA's eye and face protection regulations in 29 CFR 1910.133 or European Standard EN166.
Skin:
Wear appropriate protective gloves to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to prevent skin exposure.
Respirators:
A respiratory protection program that meets OSHA's 29 CFR 1910.134 and ANSI Z88.2 requirements or European Standard EN 149 must be followed whenever workplace conditions warrant respirator use.

---

Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Solid
Color: white
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: Not available.
Autoignition Temperature: Not available.
Flash Point: Not available.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water:
Specific Gravity/Density:
Molecular Formula: C7H15Cl2N2O4P
Molecular Weight: 293.09

---

Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable at room temperature in closed containers under normal storage and handling conditions.
Conditions to Avoid:
Dust generation.
Incompatibilities with Other Materials:
Strong oxidizing agents.
Hazardous Decomposition Products:
Hydrogen chloride, nitrogen oxides, carbon monoxide, oxides of phosphorus, carbon dioxide.
Hazardous Polymerization: Has not been reported

---

Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 39800-16-3: RP5900000 LD50/LC50:
Not available.
Carcinogenicity:
4-Hydroxyperoxycyclophophamide - Not listed by ACGIH, IARC, or NTP.
Other:
See actual entry in RTECS for complete information.

---

Section 12 - ECOLOGICAL INFORMATION

---

Section 13 - DISPOSAL CONSIDERATIONS
Products which are considered hazardous for supply are classified as Special Waste and the disposal of such chemicals is covered by regulations which may vary according to location. Contact a specialist disposal company or the local waste regulator for advice. Empty containers must be decontaminated before returning for recycling.

---

Section 14 - TRANSPORT INFORMATION

IATA
Not regulated as a hazardous material.
IMO
Not regulated as a hazardous material.
RID/ADR
Not regulated as a hazardous material.

---

Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: Not available.
Risk Phrases:
Safety Phrases:
S 24/25 Avoid contact with skin and eyes.
WGK (Water Danger/Protection)
CAS# 39800-16-3: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 39800-16-3 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 39800-16-3 is not listed on the TSCA inventory.
It is for research and development use only.

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

生物活性方面，4-羟基过氧化环磷酰胺是环磷酰胺的活性代谢产物形式。它通过交联DNA诱导T细胞凋亡，这种凋亡不依赖于死亡受体激活，并可通过产生活性氧（ROS）激活线粒体死亡途径。因此，4-羟基过氧化环磷酰胺具有潜在的研究价值，可用于淋巴瘤和自身免疫性疾病的治疗。

反应信息

• 作为反应物：
  描述：

  培磷酰胺 在 三氟乙酸 、 亚磷酸三乙酯 作用下， 反应 2.0h， 生成 4-{2-[bis-(2-chloro-ethyl)-amino]-2-oxo-2λ⁵-[1,3,2]oxazaphosphinan-4-ylsulfanylmethyl}-benzoic acid
  参考文献：
  名称：

  Synthesis of activated cyclophosphamide derivatives bearing functional groups

  摘要：

  DOI：

  10.1016/s0040-4039(01)93578-6
• 作为产物：
  描述：

  环磷酰胺 在 臭氧 作用下， 生成 培磷酰胺
  参考文献：
  名称：

  活化的N-（2-氯乙基）氨基草氮磷衍生物的质谱表征。

  摘要：

  抗肿瘤药环磷酰胺（2-双（2-氯乙基）氨基四氢-2H-1,3,2-氧杂氮膦2-氧化物），异环磷酰胺（3-（2-氯乙基）-2-（ 2-氯乙基氨基）四氢-2H-1,3,1-氧杂磷膦2-氧化物）和Trofosfamide（3-（2-氯乙基）-2-（双（2-氯乙基）氨基）四氢-2H-1,3,2电子撞击和场解吸质谱法表征-氧杂氮杂膦酸2-氧化物）。该化合物是环磷酰胺（异环磷酰胺，Trofosfamide）的活化羟基化中间体的稳定衍生物，可以鉴定为4-氢过氧和4-烷硫基氧杂氮杂膦。这些产物的非对映异构体的存在通过薄层色谱法和fd质谱证实。发现用苄基硫醇衍生是从生物材料中定量分离和质谱鉴定环磷酰胺活化的代谢中间体的合适方法。使用该反应，在用3H-环磷酰胺治疗的患者的尿液和血清中检测到不稳定的4-羟基环磷酰胺及其无环互变异构体aldophosphamide。

  DOI：

  10.1002/bms.1200040404

文献信息

• O-Methylhydroxylamine as a New Trapping Reagent for Quantitative Studies of 4-Hydroxycyclophosphamide and Aldophosphamide
  作者：Gerald Zon、Susan Marie Ludeman、Edward M. Sweet、William Egan、Lawrence R. Phillips

  DOI：10.1002/jps.2600710417

  日期：1982.4

  aldophosphamide) are quantitatively converted by O-methylhydroxylamine, at pH 7.4 and 37 degrees, into the E and Z isomers of aldophosphamide O-methyl oxime. These trapping products are readily extracted from aqueous media with either chloroform or ethyl acetate, are stable at pH 6-8 toward oxime hydrolysis and elimination of phosphoramide mustard (a secondary metabolite of cyclophosphamide), and showed

  31 P和1 H-NMR光谱用于证明抗癌药环磷酰胺（4-羟基环磷酰胺及其无环互变异构体，醛基磷酰胺）的主要代谢物在pH 7.4和37度下被O-甲基羟胺定量转化为E和醛磷酸酰胺O-甲基肟的Z异构体。这些捕获产物很容易用氯仿或乙酸乙酯从水性介质中提取，在pH 6-8时对肟水解和消除磷酰胺芥子（环磷酰胺的次生代谢产物）稳定，并且没有证据表明酮或醛可以进行过氧肟化接受者。所有这些特征均支持在与环磷酰胺代谢有关的定量研究中使用醛磷酸酰胺O-甲基肟。
• STEEN J. VAN DER; WESTRA J. G.; BENCKHUYSEN C.; SCHULTEN H.-R., J. AMER. CHEM. SOC., 1980, 102, NO 17, 5691-5692
  作者：STEEN J. VAN DER、 WESTRA J. G.、 BENCKHUYSEN C.、 SCHULTEN H.-R.

  DOI：——

  日期：——
• ZON, G.;LUDEMAN, S. M.;SWEET, E. M.;EGAN, W.;PHILLIPS, L. R., J. PHARM. SCI., 1982, 71, N 4, 443-446
  作者：ZON, G.、LUDEMAN, S. M.、SWEET, E. M.、EGAN, W.、PHILLIPS, L. R.

  DOI：——

  日期：——
• HIRANO TAKASHI; KLESSE W.; HEUSINGER J. H.; LAMBERT G.; RINGSDORF H., TETRAHEDRON LETT., 1979, NO 10, 883-886
  作者：HIRANO TAKASHI、 KLESSE W.、 HEUSINGER J. H.、 LAMBERT G.、 RINGSDORF H.

  DOI：——

  日期：——
• Phosphorus-31 nuclear magnetic resonance spectroscopic observation of the intracellular transformations of oncostatic cyclophosphamide metabolites
  作者：Victoria L. Boyd、Joan D. Robbins、William Egan、Susan M. Ludeman

  DOI：10.1021/jm00157a015

  日期：1986.7

  31P NMR spectroscopy was used to directly monitor, for the first time, the intracellular chemistry of the ultimate active metabolite of cyclophosphamide, namely, phosphoramide mustard. These NMR studies utilized a human histiocytic lymphoma cell line (U937), embedded in agarose gel threads, and perfused with medium containing synthetically derived metabolites (4-hydroxycyclophosphamide, aldophosphamide, and phosphoramide mustard). Metabolites 2 or 3 or both readily crossed the cell membrane; in contrast, the membrane was relatively impermeable to 4. Intracellular concentrations of 4 could, therefore, be attributed primarily to the intracellular fragmentation of 3. Signals suggestive of either carboxyphosphamide or 4-ketophosphamide were not detected. Spectral data were used to calculate a rate constant of (5.4 +/- 0.3) X 10(-3) min-1 for the intracellular disappearance of 4 at 23 degrees C. The intracellular pH was determined to be 7.1 from the chemical shift of the internal inorganic phosphate signal.