pinacolyl methylphosphonochloridate | 7040-57-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: pinacolyl methylphosphonochloridate
• 英文别名: 1,2,2-Trimethylpropyl methylphosphonochloridate；O-pinacolyl methylphosphonochloridate；Pinacolyl-methylphosphonsaeurechlorid；Methylphosphonsaeure-(1,2,2-trimethyl-propylester)-chlorid；Methylphosphonsaeure-pinacolylester-chlorid；Chlorosoman；3-[chloro(methyl)phosphoryl]oxy-2,2-dimethylbutane
• CAS: 7040-57-5
• 化学式: C₇H₁₆ClO₂P
• 分子量: 198.63
• InChiKey: XVNBZVNXJMOQEX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  11
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

ADMET

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中毒物洗消。如果患者停止呼吸，立即开始人工呼吸，最好使用需求阀复苏器、袋阀面罩装置或口袋面罩，按培训操作。根据需要执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果患者呕吐，让患者身体前倾或置于左侧卧位（如果可能的话，头部向下），以保持呼吸道畅通，防止吸入性肺炎。保持患者安静，维持正常体温。寻求医疗帮助。 /神经毒剂/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand-valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR as necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Nerve Agents/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。可能需要积极控制气道。观察呼吸不足的迹象，如有必要，协助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，如有必要，进行治疗……。监测休克，如有必要，进行治疗……。预期可能出现癫痫，如有必要，进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在转运过程中，用0.9%的生理盐水（NS）连续冲洗每只眼睛……。/神经毒剂/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Aggressive airway control may be needed. Watch for signs of respiratory insufficiency and assist ventilations it necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . /Nerve Agents/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 高级治疗：对于无意识、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩的正压通气技术可能有益。初始通气可能困难。由于分泌物和支气管收缩，气道阻力可能较高（50至70 cm H2O）。可能需要频繁抽吸。监测心率和必要时治疗心律失常...开始静脉输注D5W /SRP: "保持开放"，最小流量/。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸林格液（LR）。对于伴有低血容量迹象的低血压，谨慎给予液体。如果病人在正常血容量时低血压，考虑使用血管加压药。注意液体过载的迹象...给予阿托品。在给药前纠正低氧血症...对于严重中毒的病人，给予氯磷定（2-PAM）。...用适量的阿托品化、纠正低氧血症和必要时使用地西泮（安定）或劳拉西泮治疗癫痫...在大规模伤亡事件中建议使用自动注射器阿托品和2-PAM。这些自动注射器被称为Mark I ket。也有自动注射器地西泮可用...。给予缩瞳剂和眼痛的homatropine滴眼液...。使用丙美卡因氢氯化物协助眼部冲洗...。/神经毒剂/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag-valve-mask device may be beneficial. Initial ventilation may be difficult. Airway resistance may be high (50 to 70 cm H2O) because of secretions and bronchoconstriction. Frequent suctioning may be necessary. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Consider vasopressors if patient is hypotensive with a normal fluid volume. Watch for signs of fluid overload ... . Administer atropine. Correct hypoxia before administration ... . In severely poisoned patients, administer pralidoxime chloride (2-PAM). ... Treat seizures with adequate atropinization, correction of hypoxia, and diazepam (Valium) or lorazepam as necessary ... . In mass casualty events the use of auto-injector atropine and 2-PAM is advised. These auto-injectors are know as the Mark I ket. An auto-injector diazepam is also available ... . Administer homatropine drops for miosis and eye pain ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Nerve Agents/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

在本研究中，研究了14C标记的松香醇甲基磷酰氯(PiCl)与牛胸腺DNA的体外结合。数据显示，在PiCl浓度为0.038-0.26 mM时，结合是迅速的，并且在每2000个核苷酸修饰一个PiCl分子的程度上是可饱和的。相似的PiCl浓度范围具有毒性，但在鼠伤寒沙门氏菌TA100和TA98中并未产生显著的突变增加。这些结果对于评估体外梭曼样有机磷化合物及其相关杀虫剂的突变风险具有重要意义。

/GENOTOXICITY/ In the present study, in vitro binding of 14C-labeled pinacolyl methylphosphonochloridate (PiCl) to calf-thymus DNA has been investigated. The data reveal that, at PiCl concentrations of 0.038-0.26 mM, the binding is rapid and saturable at the extent of modification of 1 PiCl molecule per 2000 nucleotides. A similar range of PiCl concentrations was toxic, but did not produce a significant increase in mutagenicity in Salmonella typhimurium TA100 and TA98. /The/ results are of relevance with regard to the in vitro assessment of Soman-like organophosphates and the mutagenic risk of these agents and related pesticides.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性值

LD50（小白鼠皮下注射）185毫克/千克 这里的LD50指的是半数致死剂量，即能够导致50%的实验动物死亡的剂量。小白鼠皮下注射指的是实验中给药的方式。185毫克/千克则是给药剂量与实验动物体重的比例。

LD50 Mouse sc 185 mg/kg

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  pinacolyl methylphosphonochloridate 在 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 生成 N-hydroxy-4-nitrobenzimidic (3,3-dimethylbutan-2-yl methylphosphonic) anhydride
  参考文献：
  名称：

  有机磷化合物的反应性。第二十七部分。烷基膦酸氢烷基酯与对硝基苯甲腈氧化物的反应：酸性水解得到的α-羟基亚氨基对硝基苯甲酸烷基膦酸酯的无规辅助的P-O裂变

  摘要：

  p -Nitrobenzonitrile与烷基氢烷基膦容易氧化物反应（I; R 1 =我，R 2 =甲基，乙基，镨，镨我，卜吨CH 2，或卜吨CHME）和（I; R 1 =的Et，卜t或Ph; R 2 = Et），磷酸二乙基氢和二乙基次膦酸氢生成相应的1：1加合物，即烷基α-羟基亚氨基-对硝基苄基烷基膦酸酯（II; R 1 = Me; R 2 = Me，乙基，丙基，镨我，卜吨CH 2，或卜吨CHME）和（II; R 1=的Et，卜吨或pH; [R 2 = ET），二乙基α羟基亚p硝基苄酯（II; R 1 =环氧乙烷，R 2 = ET），和α羟基亚p分别硝基苄二乙基次膦酸（III）。除了在酸性条件下稳定的最后一种情况外，加合物在稀有的二恶烷水溶液中在pH 2-3·5的条件下，以非常快速的，通过手性辅助的方式发生了P–O裂变（动力学研究表明，其快约10 7，比在相似条件下经历烷基-氧裂变的简单

  DOI：

  10.1039/j29710001988
• 作为产物：
  描述：

  甲基膦酞二氯 、 3,3-二甲基-2-丁醇 在 三乙胺 作用下， 以 苯 为溶剂， 以71%的产率得到pinacolyl methylphosphonochloridate
  参考文献：
  名称：

  磷酸化肽的固相合成

  摘要：

  我们报告了使用 Fmoc 保护的氨基酸固相合成两个系列的膦酰化肽。这些肽对应于丁酰胆碱酯酶活性位点中含有磷酸化 Ser195 和人血清白蛋白 Tyr411 的区域。磷酸化 Fmoc 保护的氨基酸用于固相肽合成以制备肽。具有苄酯保护的 Fmoc-丝氨酸和 Fmoc-酪氨酸用烷基甲基膦酸一氯化物处理以膦酰化侧链羟基。膦酰化肽被设计为模拟蛋白质暴露于有机磷试剂后的蛋白质区域。

  DOI：

  10.1055/s-0030-1258132

文献信息

• Analogues with Fluorescent Leaving Groups for Screening and Selection of Enzymes That Efficiently Hydrolyze Organophosphorus Nerve Agents
  作者：Luis Briseño-Roa、Jim Hill、Stuart Notman、David Sellers、Andy P. Smith、Christopher M. Timperley、Janet Wetherell、Nichola H. Williams、Gareth R. Williams、Alan R. Fersht、Andrew D. Griffiths

  DOI：10.1021/jm050518j

  日期：2006.1.1

  and dimefox, and the nerve agents DFP, tabun, sarin, cyclosarin, soman, VX, and Russian-VX. Data from inhibition of acetylcholinesterase, in vivo toxicity tests of a representative analogue (cyclosarin), and kinetic studies with phosphotriesterase (PTE) from Pseudomonas diminuta, and a mammalian serum paraoxonase (PON1), confirmed that the analogues mimic the parent nerve agents effectively. They are

  有效水解剧毒有机磷神经毒剂的酶可能被用作医疗对策。由于目前尚不清楚足够活跃的酶，我们合成了十二种具有 3-氯-7-氧基-4-甲基香豆素离去基团的有机磷神经毒剂荧光类似物作为高通量酶筛选的探针。这组包括杀虫剂对氧磷、对硫磷和二甲硫磷的类似物，以及神经毒剂 DFP、塔崩、沙林、环沙林、索曼、VX 和俄罗斯-VX。来自乙酰胆碱酯酶抑制的数据、代表性类似物（环沙林）的体内毒性试验以及来自 Pseudomonas diminuta 的磷酸三酯酶 (PTE) 和哺乳动物血清对氧磷酶 (PON1) 的动力学研究证实，这些类似物有效地模拟了亲本神经毒剂。
• Fragmentation mechanisms in mass spectrometry of organophosphorus compounds: implications for analysis in chemical weapons convention framework
  作者：Hamid Saeidian、Mansour Sarabadani

  DOI：10.1007/s13738-014-0563-y

  日期：2015.6

  Detection and identification of chemical warfare agents and their precursors/reaction products in various environmental matrices are important tasks which are considered in chemical weapons convention (CWC). 2-[(2-chloroethyl)(alkyl)amino]ethyl alkyl methylphosphonates I and N-alkyl bis(2-(alkoxy-methylphosphoryloxy)amines II are covered under schedule 2.B.4 of CWC and have structures closely related

  在各种环境基质中检测和识别化学战剂及其前体/反应产物是化学武器公约（CWC）中考虑的重要任务。2-[（2-氯乙基）（烷基）氨基]乙基烷基甲基膦酸酯I和N-烷基双（2-（烷氧基-甲基磷酰氧基）胺II在《化学武器公约》附表2.B.4中涵盖，其结构与神经和水泡剂密切相关。实际上，它们是这两种不同的CWC预定化合物之间的反应产物：神经毒剂和氮芥。使用电子电离质谱法研究了这些化学物质的质谱研究过程中的离子碎片。使用氘化类似物的EI-MS分析确认片段的结构。密度泛函理论也被用来显示优选的断裂途径。质谱研究揭示了一些碎片化途径，例如麦克拉菲型和氢重排以及消除了氯，氯亚甲基，烯烃和HCl。
• New simulators in the prophylaxis against soman poisoning: structural specificity for the depot site(s)
  作者：Herman P M Van Helden、Henk P Benschop、Otto L Wolthuis

  DOI：10.1111/j.2042-7158.1984.tb04379.x

  日期：2011.4.12

  The oxime HI−6 is effective as an antidote in the soman poisoned (6–8LD50) rat, however, successfully treated animals subsequently show a gradual relapse of signs of poisoning and eventually die after several hours. The relapse is caused by the reappearance of soman at specific sites, after having been elsewhere in the body. Diaphragms isolated from poisoned rats successfully treated with HI−6 also showed a ‘secondary’ relapse of poisoning. Eight compounds chemically related to soman-soman-simulators–-have been tested as prophylactic agents, for their potency in preventing the reappearance of poisoning. The idea was that such compounds may block the non-synaptic binding sites for soman. Three of the 8 compounds proved very effective, which gave some insight into the chemical structure needed for this type of prophylactic action.

  氢肟HI-6在中毒（6-8LD50）的老鼠中作为解毒剂是有效的，但成功治疗的动物随后显示出中毒症状的逐渐复发，并在几个小时后死亡。复发是由特定部位的索曼再次出现引起的，在此之前，它已经在身体的其他部位。用HI-6成功治疗的中毒老鼠分离的膈肌也显示出毒性的“次生”复发。已经测试了与索曼相关的8种化合物-索曼模拟剂-作为预防剂，以防止中毒症状的复发。这样的化合物可能会阻止索曼的非突触结合位点。其中8种化合物中的3种被证明非常有效，这为这种预防性行动所需的化学结构提供了一些见解。

• Microwave Induced Synthesis of O,O-Dialkyl Dialkylpyrophosphonates under Solvent Free Conditions: Markers of Nerve Agents
  作者：Rajesh Kumar、Deepak Pardasani、Avik Mazumder、Devendra K. Dubey、Arvind K. Gupta

  DOI：10.1071/ch07375

  日期：——

  This article describes a one pot, solvent free, microwave assisted synthesis of O,O-dialkyl dialkylpyrophosphonates (DADAPP) from O-alkyl alkylphosphonic chlorides 2a–j with 4-dimethylaminopyridine (DMAP) in the presence of water under microwave irradiation. The reaction takes place by the phosphonium salts, which are converted into the DADAPPs 4a–j. These DADAPPs are important markers of chemical

  本文介绍了在微波辐射下，在水存在下，由 O-烷基烷基膦酰氯 2a-j 与 4-二甲氨基吡啶 (DMAP) 合成 O,O-二烷基二烷基焦膦酸盐 (DADAPP) 的一锅无溶剂微波辅助合成方法。该反应由鏻盐发生，鏻盐转化为 DADAPP 4a-j。这些 DADAPP 是化学战剂沙林、梭曼和 VX 及其类似物的重要标志。与传统方法相比，该方法具有操作简单、产率高、反应时间短等优点。
• Chemical and biochemical adducts as biomarkers for organophosphate exposure
  申请人：Human BioMolucular Research Institute

  公开号：US10711037B2

  公开（公告）日：2020-07-14

  Provided are methods for identifying OP-adducted biomarkers of OP exposure as well as compounds containing OPs that can provide OP adducts and compounds of Formula 1 for eliciting antibodies that specifically and selectively bind to the OP adducts, wherein the Formula 1 compounds have the structure of OP-Peptide-Linker-CP, wherein CP is a carrier protein, OP represents a structure corresponding to that of a reactive organic phosphorous compound covalently modifying a tyrosine residue hydroxyl group of the peptide of Formula I and the other variable groups are as described herein.

  本发明提供了用于鉴定 OP 暴露的 OP 加合物生物标志物的方法以及含有 OP 的化合物，这些化合物可提供 OP 加合物和用于激发特异性和选择性结合 OP 加合物的抗体的式 1 化合物，其中式 1 化合物具有 OP-Peptide-Linker-CP 结构，其中 CP 是载体蛋白，OP 代表与共价修饰式 I 肽的酪氨酸残基羟基的活性有机磷化合物结构相对应的结构，其他可变基团如本文所述。