氟乙酸 | 144-49-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 氟乙酸
• 中文别名: 氟醋酸；一氟醋酸；一氟乙酸
• 英文名称: Fluoroacetic acid
• 英文别名: 2-fluoroacetic acid；monofluoroacetic acid
• CAS: 144-49-0
• 化学式: C₂H₃FO₂
• mdl: MFCD00039529
• 分子量: 78.043
• InChiKey: QEWYKACRFQMRMB-UHFFFAOYSA-N

物化性质

• 熔点：
  35.2 °C
• 沸点：
  165 °C
• 密度：
  1.3693 g/cm3(Temp: 36 °C)
• 物理描述：
  Fluoroacetic acid appears as a colorless crystalline solid. May be toxic by ingestion. Used to make other chemicals.
• 颜色/状态：
  Needles
• 溶解度：
  Miscible with water (1.0X10+6 mg/L) at 25 °C
• 蒸汽压力：
  1.27 mm Hg at 25 °C
• 亨利常数：
  1.24e-08 atm-m3/mole
• 稳定性/保质期：
  1. 稳定性：稳定。 2. 禁配物：强氧化剂、碱类。 3. 避免接触的条件：受热。 4. 聚合危害：不聚合。 5. 分解产物：氟化氢。
• 分解：
  When heated to decomposition, it emits highly toxic fumes of /hydrogen fluoride and sodium oxides/.
• 解离常数：
  pKa = 2.59

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  5
• 可旋转键数：
  1
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  3

ADMET

代谢

氟乙酸被代谢转化为氟柠檬酸，后者抑制三羧酸循环，导致细胞缺氧。

/Fluoroacetic acid is/ metabolically converted to fluorocitrate which inhibits the tricarboxylic acid cycle resulting in cellular hypoxia.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在大鼠中，肾皮质线粒体积极产生的氟柠檬酸盐比对照组高出700%以上。确定了氟柠檬酸盐激活的两条途径。1与丙酮酸代谢相关，不依赖于氧化磷酸化能量；另一条与乙酸盐代谢相关，且依赖于ATP。

In rats, mitochondria from kidney cortex actively produced fluorocitrate more than 700% above control. Two pathways of fluorocitrate activation identified. 1 associated with pyruvate metabolism and not dependent on oxidative phosphorylation energy /and another/ associated with acetate metabolism and is ATP dependent.

来源:Hazardous Substances Data Bank (HSDB)

代谢

氟乙酸盐通过腹腔注射给予大鼠和小鼠后，会被脱氟生成氟离子，这在尿液和肾脏中通过^19F NMR检测到。使用^13C-2-、^13C-1,2-和^14C-1,2-氟乙酸盐...揭示了尿液中存在复杂的代谢物混合物，包括在大鼠和小鼠中的S-(羧甲基)结合复合物以及在大鼠中的亚磺酰化产物...。...在用^13C-2-氟乙酸盐处理后，胆汁中出现了S-(羧甲基)谷胱甘肽或相关结合物以及氟乙酸盐的O-结合物。将^13C-氟乙酸盐与大鼠和小鼠肝脏细胞溶质一起培养，会形成S-((^13C-羧甲基))谷胱甘肽和氟离子。氟柠檬酸也在小鼠肝脏细胞溶质与氟乙酸盐培养中被检测到。腹腔注射氟乙酰胺给大鼠和小鼠后，会通过氟乙酸盐在尿液中形成氟离子，这是在有机磷酸盐敏感的酰胺酶水解作用下释放的。(^19)F NMR...显示氟乙酰胺的其他代谢物与小鼠肝脏中的氟乙酰羟胺酸一致，以及大鼠尿液中的氟柠檬酸。氟乙醇在大鼠和小鼠中产生尿液中氟乙酸盐和氟离子，并且通过小鼠和大鼠肝脏微粒体转化为氟乙醛。(-)-和(+)-苏式-氟柠檬酸通过腹腔注射给予大鼠后，在6小时内主要在尿液中排出母体化合物，此后氟离子的量逐渐增加。...大鼠和小鼠肝脏细胞溶质脱氟(-)-苏式-氟柠檬酸。代谢脱氟和猪心肌酶也能脱氟(-)-苏式-氟柠檬酸。因此，氟乙酸盐及其前身氟乙酰胺和氟乙醇的代谢脱氟可归因于氟乙酸盐与谷胱甘肽的结合以及转化为(-)-苏式-氟柠檬酸，后者既是酶的抑制剂也是底物。...用氟乙酸盐或(-)-苏式-氟柠檬酸中毒的大鼠和小鼠的尿液中，柠檬酸和葡萄糖含量升高，尿素含量降低，这与三羧酸循环和氨代谢的紊乱一致。

Fluoroacetate administered ip to rats and mice is defluorinated to give fluoride ion evident in urine and kidney by (19)F NMR. The use of 2-(13)C-, 1,2-(13)C-, and 1,2-(14)C-fluoroacetate, ... reveals a complex mixture of urinary metabolites including an S-(carboxymethyl) conjugate complex in rats and mice and sulfoxidation products... in rats. ...Bile, following treatment with 2-(13)C- fluoroacetate, shows the presence of S-(carboxymethyl)glutathione or a related conjugate and an O-conjugate of fluoroacetate. Incubation of (13)C-fluoroacetate with rat and mouse liver cytosol involves formation of S-((13)C-carboxymethyl) glutathione and fluoride ion. Fluorocitrate is also /detected in/ fluoroacetate incubations with mouse liver cytosol. Fluoroacetamide administered ip to rats and mice yields urinary fluoride ion formed via fluoroacetate which is liberated on hydrolysis by an organophosphate-sensitive amidase. (19)F NMR... of other metabolites of fluoroacetamide are consistent with fluoroacetohydroxamic acid in the liver of mice and fluorocitrate in the urine of rats. Fluoroethanol gives urinary fluoroacetate and fluoride ion in rats and mice and is converted to fluoroacetaldehyde by mouse and rat liver microsomes. (-)- and (+)-erythro- fluorocitrates administered ip to rats yield mostly the parent compounds in urine at 6 hr with increasing amounts of fluoride ion thereafter. ...Rat and mouse liver cytosols defluorinate (-)-erythro-fluorocitrate. Metabolic defluorination and pig heart aconitase also defluorinates (-)-erythro- fluorocitrate. Metabolic defluorination of fluoroacetate and its progenitors, fluoroacetamide and fluoroethanol, is therefore attributable to both conjugation of fluoroacetate with glutathione and conversion to (-)-erythro-fluorocitrate, which is both an inhibitor of and a substrate for aconitase. ...Urine of rats and mice poisoned with fluoroacetate or (-)-erythro-fluorocitrate show elevated citrate and glucose and diminished urea consistent with disruptions in the tricarboxylic acid cycle and ammonia metabolism.

来源:Hazardous Substances Data Bank (HSDB)

代谢

氟乙酸离子本身无毒，但在体内会形成氟柠檬酸，后者在柠檬酸阶段阻断细胞代谢。症状出现有延迟，但氟柠檬酸的致死合成会导致不可逆的细胞功能障碍，特别是在中枢神经系统和循环系统。中毒可以用单乙醯甘油和乙酰胺治疗。

...Fluoroacetic ion alone is non-toxic but in vivo forms fluorotricarboxylic acid, which blocks cellular metabolism at the citrate stage. Symptoms occur with a delay but lethal synthesis of fluorotricarboxylic acid leads to the irreversible cellular dysfunction, especially in CNS and circulatory system. Poisoning may be treated with monoacetin and acetamide.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别和使用：氟乙酸是一种固体。它曾用于生产高度有毒的灭鼠剂和一般哺乳动物害虫控制剂——氟乙酸钠。人类研究：估计氟乙酸对人类的致死剂量在2至10毫克/千克的范围内。在新西兰，一名兔子捕杀者在10年期间反复接触氟乙酸诱饵的准备过程中，出现了慢性中毒。他表现出严重的、进行性的肾小管上皮细胞病变，以及较轻的肝脏、神经和甲状腺功能障碍。在另一个案例中，一名化学家在潜伏期0.5至数小时后出现中毒症状，随后迅速死亡。抽搐和心律不齐是常见的死亡征兆。尸检时没有发现特定的变化。氟乙酸根离子本身无毒，但在体内会形成氟三羧酸，这会阻断细胞在柠檬酸阶段的代谢。症状出现有延迟，但致死性的氟三羧酸合成会导致不可逆转的细胞功能障碍，尤其是在中枢神经系统和循环系统中。中毒可以用单醋酸和乙酰胺进行治疗。动物研究：给予大鼠1.0-1.5毫克/千克的氟乙酸会减少牙本质的形成和牙釉质的钙化。氟乙酸在大鼠体内的低温活性（1.5-60毫克/千克，ip）与其致死效果密切相关。大鼠比小鼠更敏感。以6毫克/千克ip给予大鼠，会逐渐耗尽ATP含量，AMP和ADP水平在最初的2小时内增加，随后下降。以4.5-15微克/千克/分钟的速度将氟乙酸注入狗的左肾动脉，持续90-240分钟，会显著增加单侧利尿，由于重吸收减少，钠、钾、钙、氯和磷酸盐的排泄量增加。类似的改变在37-936微克/千克iv给药后观察到。氟乙酸毒性通常表现为癫痫发作。在静脉注射0.03毫摩尔/千克的氟乙酸的猫中，血液中的离子钙水平在注射后40分钟平均下降了27.2%。心电图上的QT间期相应延长。世界许多植物含有单氟乙酸，会导致家畜突然死亡。这些植物主要分布在非洲、澳大利亚和南美洲的南部大陆，它们对家畜生产产生了负面影响。在山羊中，主要临床体征包括运动失调、全身肌肉震颤、基底宽大的姿势、呼吸急促、心动过速、发声和呼吸窘迫。两只山羊在观察到第一个临床体征后5分钟和20分钟内死亡。生态毒性研究：在秀丽隐杆线虫（Caenorhabditis elegans）中，添加到生长培养基中的氟乙酸将第二代繁殖率降低了50%，浓度比降低24小时生存率50%的浓度低3000倍。

IDENTIFICATION AND USE: Fluoroacetic acid is a solid. It was used formerly in the production of the highly toxic rodenticide and general mammalian pest control agent sodium fluoroacetic acid. HUMAN STUDIES: Estimates of the lethal dose of fluoroacetate in humans lie in the range of 2 to 10 mg/kg. In the case of chronic human poisoning, a rabbit exterminator in New Zealand was exposed repeatedly during preparation of fluoroacetate bait over a period of 10 years. He presented with severe and progressive lesions of the renal tubular epithelium and with milder hepatic, neurologic and thyroid dysfunctions. In another case, symptoms of poisoning in a chemist began after latent period of 0.5 to several hr followed rapidly by death. Convulsions and arrhythmia were common terminal signs. No specific changes were noted at post mortem. Fluoroacetic ion alone is non-toxic but in vivo forms fluorotricarboxylic acid, which blocks cellular metabolism at the citrate stage. Symptoms occur with a delay but lethal synthesis of fluorotricarboxylic acid leads to the irreversible cellular dysfunction, especially in CNS and circulatory system. Poisoning may be treated with monoacetin and acetamide. ANIMAL STUDIES: Administration of 1.0-1.5 mg/kg of fluoroacetate decreased dentin formation and enamel calcification in rats. Hypothermic activity of fluoroacetic acid 1.5-60 mg/kg, ip in rats was closely related to its lethal effect. Rats were more sensitive than mice. Administration of 6 mg/kg ip to rats progressively depleted ATP content, AMP and ADP levels increased during initial 2 hr and later declined. 4.5-15 ug/kg/min fluoroacetate administration into dogs left renal artery for 90-240 min sharply increased unilateral diuresis, with increased excretion of sodium, potassium, calcium, chlorides and inorganic phosphates due to decreased reabsorption. Similar changes observed after 37-936 ug/kg iv administration. Fluoroacetic acid toxicity is often characterized by seizures. In cats intravenously injected with fluoroacetate at 0.03 mmol/kg the ionized calcium level in blood fell by an average of 27.2%, 40 minutes after injection. There was a corresponding prolongation of the QT interval of the electrocardiogram. Many plants worldwide contain monofluoroacetate and cause sudden death in livestock. These plants are primarily found in the southern continents of Africa, Australia, and South America, where they negatively affect livestock production. In goats, the main clinical signs were motor incoordination, generalized muscle tremors, broad-based posture, tachypnea, tachycardia, vocalization and respiratory distress. Two goats died 5 and 20 min after the observation of the first clinical signs. ECOTOXICITY STUDIES: In the nematode Caenorhabditis elegans, fluoroacetic acid added to the growth medium reduced reproduction in the second generation by 50% at concentrations 3,000 times lower than the concentrations that reduced 24-hour survival by 50%.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

氟乙酸酯与醋酸酯相似，醋酸酯在细胞代谢中起着关键作用。氟乙酸酯通过结合辅酶A形成氟乙酰辅酶A，从而破坏柠檬酸循环。氟乙酰辅酶A然后与柠檬酸合酶反应，产生氟柠檬酸。氟柠檬酸的一个代谢物非常紧密地结合到顺乌头酸酶上，从而停止柠檬酸循环。这种抑制作用导致血液中柠檬酸的积累，使细胞缺乏能量。

Fluoroacetate is similar to acetate, which has a pivotal role in cellular metabolism. Fluoroacetate disrupts the citric acid cycle by combining with coenzyme A to form fluoroacetyl CoA. Fluoroacetyl CoA then reacts with citrate synthase to produce fluorocitrate. A metabolite of fluorocitrate binds very tightly to aconitase, thereby halting the citric acid cycle. This inhibition results in an accumulation of citrate in the blood which deprives cells of energy. (L1713) (A2849) (A2850)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌性证据

A4：无法归类为人类致癌物。/氟化物，如F/

A4: Not classifiable as a human carcinogen. /Fluorides, as F/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌物分类

对人类无致癌性（未列入国际癌症研究机构IARC清单）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

氟乙酸对眼睛、皮肤和呼吸道具有腐蚀性。它可能对心血管系统、中枢神经系统、肾脏产生影响，导致包括心脏和肾功能衰竭在内的功能障碍。暴露可能导致死亡。

Fluoroacetic acid is corrosive to the eyes, the skin and the respiratory tract. It may cause effects on the cardiovascular system, central nervous system, kidneys, resulting in impaired functions including cardiac and renal failure. Exposure may result in death. (L1685) (L138)

来源:Toxin and Toxin Target Database (T3DB)

吸收、分配和排泄

描述了一种快速提取和鉴定组织中的氟乙酰胺和氟乙酸的方法，使用气相色谱，并以多离子监测模式的质谱仪作为检测器。在动物和人体组织研磨物中添加每种化合物后，氟乙酰胺的回收率约为30-35%，氟乙酸的回收率约为50-55%。在组织中可检测到的最低水平发现氟乙酰胺约为0.7微克/克，氟乙酸约为0.1微克/克。在因这些化合物致命中毒的豚鼠和兔子的内脏组织中，氟乙酰胺的水平约为3微克/克，氟乙酸的水平为2.5-10微克/克。

A rapid method is described for the extraction and identification of fluoroacetamide and fluoroacetic acid from tissues, by gas chromatography, using a mass spectrometer in the multiple ion monitoring mode as the detector. Recoveries from animal and human tissue macerates, after the addition of each compound, were approximately 30-35% for fluoroacetamide and 50-55% for fluoroacetic acid. Minimum detectable levels in tissues were found to be circa 0.7 ug/g for the amide and 0.1 mug/g for the acid. Visceral tissue levels were found to be approximately 3 ug/g for fluoroacetamide, and 2.5-10 ug/g fluoroacetic acid in guinea pigs and rabbits which had been fatally poisoned with these compounds.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

... (14)-氟乙酸的碳同位素在给大鼠腹腔注射后缓慢排泄。4小时后，仅有1%以(14)-二氧化碳的形式排出。... 在那时，少于1%的(14)-碳通过尿液排出，60%存在于尸体中，12%在肝脏，10%在胃肠道，4%在肺，3%在肾脏，2%在大脑中。4天后... 32%... 通过尿液排出，3%以(14)-二氧化碳形式排出，大部分剩余的碳同位素可能已经通过组织吸收而保留在体内 /来自大鼠的腹腔注射/。第四天的尿液中(14)-碳的排泄量很少（0.3%）。

... (14)-carbon-fluoroacetic acid was slowly excreted after ip administration to rats. Only 1% was excreted as (14)-carbon dioxide after 4 hr. ... At that time, less than 1% of (14)-carbon had been excreted in urine, and 60% was present in carcass, 12% in liver, 10% in GI tract, 4% in lung, 3% in kidneys, and 2% in brain. After 4 days ... 32% ... excreted in urine, 3% as (14)-carbon dioxide and much of remainder had presumably been retained by incorporation into tissues /from ip administration to rats/. Urinary excretion of (14)-carbon on fourth day was slight (0.3%).

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

氟乙酸在注射后仅1分钟内在脑组织中被发现，即使那时，它的含量也低于注射量的15%。

Fluoroacetic acid was found in brain tissues for only 1 min after injection even then it was less than 15% of amount injected.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

大多数摄入的氟乙酸盐通过粪便和尿液排出。/氟乙酸盐/

Most of fluoroacetates ingested is eliminated in feces and urine. /Fluoroacetates/

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1
• 危险品标志：
  T+,N
• 安全说明：
  S20,S22,S26,S36/37/39,S45,S61
• 危险类别码：
  R20/21/22
• 海关编码：
  2915900090
• 包装等级：
  I
• 危险类别：
  6.1(a)
• 危险品运输编号：
  2642

SDS

国标编号:	61099
ＣＡＳ:	144-49-0
中文名称:	氟乙酸
英文名称:	fluoroacetic
别 名:	氟醋酸
分子式:	C 2 H 3 FO 2 ；CH 3 COOF
分子量:	78.04
熔 点:	33℃
密 度:
蒸汽压:
溶解性:	溶于水、乙醇
稳定性:	稳定
外观与性状:	无色或白色结晶固体
危险标记:	13(剧毒品)
用 途:	用于制造农药、杀鼠药

2.对环境的影响: 一、健康危害 侵入途径： 吸入、食入、经皮吸收。 健康危害：急性中毒以中枢神经系统和心脏损害为主。口服中毒时先有呕吐、大量流泻、麻木感、上腹痛、精神恍惚、恐惧感、肌肉震颤、视力障碍、后出现癫痫发作、呼吸抑制、心率紊乱和心搏骤停。患者可因心搏骤停、抽搐发作时窒息或呼吸衰竭而死亡。 二、毒理学资料及环境行为 毒性：高毒类。 急性毒性：LD504.6mg/Kg(大鼠经口)；0.28mg/Kg(大鼠经皮)；人口服2～10mg/kg，致死量。 危险特性：遇明火、高热可燃。受热分解放出有毒的氟化氢。 燃烧(分解)产物：一氧化碳、二氧化碳、氟化氢。 3.现场应急监测方法: 4.实验室监测方法: 城市废物焚化炉烟道气体中卤代有机酸的鉴定[刊，英]/Mowrer J.；Nordin J.//Chemosphere.-1987，16(6).-1181～1192 《分析化学文摘》1989.3 5.环境标准: 6.应急处理处置方法: 一、泄漏应急处理 隔离泄漏污染区，限制出入。建议应急处理人员戴自给正压式呼吸器，穿防毒服。不要直接接触泄漏物。小量泄漏：避免扬尘，用洁净的铲子收集于干燥、洁净、有盖的容器中。大量泄漏：用塑料布、帆布覆盖，减少飞散。然后收集、回收或运至废物处理场所处置。 二、防护措施 呼吸系统防护：可能接触其蒸气时，必须佩戴自吸过滤式防毒面具(全面罩)。可能接触其粉尘时，建议佩戴头罩型电动送风过滤式防尘呼吸器。 眼睛防护：呼吸系统防护中已作防护。 身体防护：穿连衣式胶布防毒衣。 手防护：戴橡胶耐酸碱手套。 其它：工作现场禁止吸烟、进食和饮水。工作毕，彻底清洗。工作服不准带至非作业场所。单独存放被毒物污染的衣服，洗后备用。保持良好的卫生习惯。 三、急救措施 皮肤接触：脱去被污染的衣着，用肥皂水和清水彻底冲洗皮肤，就医。 眼睛接触：提起眼睑，用流动清水或生理盐水冲洗，就医。 吸入：迅速脱离现场至空气新鲜处。保持呼吸道通畅。如呼吸困难，给输氧。如呼吸停止，立即进行人工呼吸。就医。 食入：催吐。洗胃给饮牛奶或蛋清。就医。 灭火方法：消防人员须佩戴防毒面具、穿全身消防服。灭火剂：雾状水、抗溶性泡沫、二氧化碳、砂土。

制备方法与用途

制备方法

1. 使用氯乙酸作为原料，与氟化钾进行反应制得。
2. 采用工业生产的氟乙酸钠与硫酸混合后蒸馏得到。

合成制备方法

1. 使用氯乙酸为原料，与氟化钾反应制取。

反应信息

• 作为反应物：
  描述：

  氟乙酸 在 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 氟乙酸酐
  参考文献：
  名称：

  [EN] IMIDAZOPYRROLIDINONE DERIVATIVES AND THEIR USE IN THE TREATMENT OF DISEASE
  [FR] DÉRIVÉS IMIDAZOPYRROLIDINONE ET LEUR UTILISATION DANS LE TRAITEMENT DE MALADIES

  摘要：

  本发明提供了化合物(I)或其药学上可接受的盐；制造本发明化合物的方法及其治疗用途。本发明还提供了药理活性剂的组合和药物组合物。

  公开号：

  WO2014191894A1
• 作为产物：
  描述：

  sodium fluoroacetate 在 盐酸 作用下， 以 水 为溶剂， 以5.0 g的产率得到氟乙酸
  参考文献：
  名称：

  银催化杂芳烃与α-氟代羧酸的单氟烷基化：溶剂效应的洞察

  摘要：

  已经开发了一种温和有效的方法，用于用易于获得且廉价的 α-氟羧酸直接 C-H 单氟烷基化杂芳烃。这种银催化的反应在温和条件下以良好的收率提供单和双单氟烷基化杂芳烃，并详细讨论了溶剂对单氟烷基化反应的影响。

  DOI：

  10.1039/d1cc06466e
• 作为试剂：
  描述：

  吡啶 在 氟乙酸 作用下， 以 二氯甲烷 为溶剂， 25.0~60.0 ℃ 、90.0 kPa 条件下， 反应 5.5h， 以82.1%的产率得到2-氯吡啶
  参考文献：
  名称：

  一种合成2-氯吡啶的方法

  摘要：

  本发明公开了一种合成2-氯吡啶的方法。该方法的步骤为将吡啶和溶剂加入到500mL的容器中，压力控制在常压条件，搅拌10-20min，然后滴加醋酸氟，控制温度不超过30℃；将反应混合物移至500mL容器中，升温至50℃-70℃，真空度0.07-0.09MPa的条件下进行减压蒸馏，等到没有液体蒸出之后，剩余的物料即为2-氯吡啶。本发明方法的氯化并不需要氯气、三氯化磷、五氯化磷、三氯氧磷和光气等剧毒物质作为氯代试剂，而是用了二氯甲烷作为氯代试剂，工艺生产安全可靠；反应在常温常压下进行，2-氯吡啶的产率达到80％。

  公开号：

  CN105669534A

文献信息

• [EN] METHODS OF TREATMENT OF AMYLOIDOSIS USING ASPARTYL-PROTEASE INIHIBITORS<br/>[FR] PROCEDES DE TRAITEMENT D'AMYLOIDOSE UTILISANT DES INHIBITEURS DE PROTEASE ASPARTYLE
  申请人：ELAN PHARM INC

  公开号：WO2005070407A1

  公开（公告）日：2005-08-04

  The invention relates to acetyl 2-hydroxy-1,3-diaminospirocyclohexanes and derivatives thereof that are useful in treating diseases, disorders, and conditions associated with amyloidosis. Amyloidosis refers to a collection of diseases, disorders, and conditions associated with abnormal deposition of A-beta protein.

  这项发明涉及乙酰2-羟基-1,3-二氨基螺环己烷及其衍生物，可用于治疗与淀粉样变性相关的疾病、疾病和症状。淀粉样变性是指与A-beta蛋白异常沉积相关的一系列疾病、疾病和症状。
• Synthetic Routes towards Fluorine-Containing Amino Sugars: Synthesis of Fluorinated Analogues of Tomosamine and 4-Amino-4-deoxyarabinose
  作者：Christopher Albler、Walther Schmid

  DOI：10.1002/ejoc.201301614

  日期：2014.4

  Fluorinated analogues of bioactive amino sugars are of high interest in medicinal chemistry. We developed a straightforward synthetic route towards this class of carbohydrates by applying a titanium-mediated aldol addition. Thus, two-carbon chain elongations of serine- and threonine-derived aldehydes with a chiral fluoroacetyl-oxazolidinone could be achieved in good yields and excellent diastereoselectivities

  生物活性氨基糖的氟化类似物在药物化学中具有很高的兴趣。我们通过应用钛介导的羟醛添加，开发了一种直接合成此类碳水化合物的路线。因此，丝氨酸和苏氨酸衍生的醛与手性氟乙酰-恶唑烷酮的双碳链延长可以以良好的产率和优异的非对映选择性实现，以产生含氟代醇的碳骨架。一个短的脱保护序列随后分别提供了各种 4-氨基-2-氟戊糖和-己糖的吡喃形式。天然丰富的 4-氨基-4-脱氧阿拉伯糖和 4-氨基-4,6-二脱氧半乳糖（tomosamine）的立体选择性合成证明了该策略的多功能性。
• Organocatalytic Enantioselective Synthesis of α-Fluoro-β-amino Acid Derivatives
  作者：Matthew R. Straub、Vladimir B. Birman

  DOI：10.1021/acs.orglett.8b03297

  日期：2018.12.7

  catalyst HBTM-2 generates 3-fluoro-β-lactams with high enantio- and diastereoselectivity. These reactive compounds are opened with alcohols or amines to produce the corresponding α-fluoro-β-amino acid derivatives in moderate yields.

  由异硫脲催化剂HBTM-2促进的N-磺酰亚胺类化合物与氟乙酸的不对称环缩合生成具有高对映体和非对映体选择性的3-氟-β-内酰胺。这些反应性化合物用醇或胺打开，以中等产率产生相应的α-氟-β-氨基酸衍生物。
• Hapten Design and Monoclonal Antibody to Fluoroacetamide, a Small and Highly Toxic Chemical
  作者：Ling Yang、Xiya Zhang、Dongshuai Shen、Xuezhi Yu、Yuan Li、Kai Wen、Jianzhong Shen、Zhanhui Wang

  DOI：10.3390/biom10070986

  日期：——

  Fluoroacetamide (FAM) is a small (77 Da) and highly toxic chemical, formerly used as a rodenticide and potentially as a poison by terrorists. Poisoning with FAM has occurred in humans, but few reliably rapid detection methods and antidotes have been reported. Therefore, producing a specific antibody to FAM is not only critical for the development of a fast diagnostic but also a potential treatment

  氟乙酰胺（FAM）是一种小型（77 Da）的剧毒化学品，以前用作杀鼠剂，并有可能被恐怖分子用作毒药。FAM中毒已在人类中发生，但几乎没有可靠的快速检测方法和解毒剂的报道。因此，产生针对FAM的特异性抗体不仅对快速诊断的发展至关重要，而且对潜在治疗也至关重要。但是，实现这一目标是一个巨大的挑战，主要是由于FAM的分子量非常低。在这里，我们首次设计了两组FAM半抗原，借助线性脂肪族或苯基间隔基臂最大限度地暴露了氟或氨基。有趣的是，在半抗原末端带有氟的半抗原并未诱导针对FAM的抗体反应，在远端带有氨基的半抗原和含苯基的间隔臂触发了明显的特异性抗体反应。最后，使用IC成功获得了名为5D11的单克隆抗体（mAb）50的值为97μgmL -1，与其他9个功能和结构类似物的交叉反应性可忽略不计。
• Synthetic Methods and Reactions. Part 106. Suppression of anchimerically assisted rearrangement products in the synthesis of ?-fluorocarboxylic acids from ?-amino acids with 48:52 (w/w) hydrogen fluoride/pyridine [1]
  作者：George A. Olah、G. K. Surya Prakash、Yah Li Chao

  DOI：10.1002/hlca.19810640806

  日期：1981.12.16

  Anchimerically assisted rearrangement, observed in the fluorination of some α-amino acids with 70 : 30 (w/w) hydrogen fluoride/pyridine (by weight) in the presence of NaNO2, is substantially or fully suppressed by using the less acidic reagent 48 : 52 (w/w) hydrogen fluoride/pyridine.

  Anchimerically辅助重排，在一些α氨基酸的氟化观察到70：纳米的存在30（重量/重量）氟化氢/吡啶（按重量计）2，通过使用更少的酸性试剂48基本上或完全抑制：52（w / w）氟化氢/吡啶。

表征谱图