1-(4-甲氧基苄基)乙胺 | 64-13-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 1-(4-甲氧基苄基)乙胺
• 中文别名: 1-(4-甲氧基苯基)-2-丙胺；苯基脲；β-苯乙胺；苯基尿素
• 英文名称: 2-amino-1-(4-methyoxyphenyl)propane
• 英文别名: para-methoxyamphetamine；4-Methoxyamphetamine；1-(4-methoxyphenyl)propan-2-amine
• CAS: 64-13-1
• 化学式: C₁₀H₁₅NO
• 分子量: 165.235
• InChiKey: NEGYEDYHPHMHGK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  2

ADMET

代谢

苯丙胺（AM）及其五种衍生物，N-乙基苯丙胺（NEA）、N-丁基苯丙胺（NBA）、4-甲氧基苯丙胺（M-AM）、4-甲氧基-N-乙基苯丙胺（M-NEA）和4-甲氧基-N-丁基苯丙胺（M-NBA）与表达人类CYP2D6酶的细胞微粒体准备物一起孵化，以确定该酶是否能够催化所有底物的直接环氧化；NEA、NBA、M-NEA和M-NBA的N-脱烷基化；以及M-AM、M-NEA和M-NBA的O-去甲基化。检查的六种化合物中没有一种发生了任何程度的N-脱烷基化。由AM、NEA和NBA产生的唯一代谢物是相应的环4-羟基化合物，且形成速率较低。所有环4-甲氧基化底物都被CYP2D6有效地O-去甲基化为相应的酚。N-烷基团的大小影响了这些酚胺的形成速率。与2-和3-甲氧基苯丙胺的报道发现不同，在CYP2D6酶系统中，没有任何4-甲氧基苯丙胺被环氧化为2-或3-羟基-4-甲氧基苯丙胺或二羟基苯丙胺。

Amphetamine (AM) and five amphetamine derivatives, N-ethylamphetamine (NEA), N-butylamphetamine (NBA), 4-methoxyamphetamine (M-AM), 4-methoxy-N-ethylamphetamine (M-NEA) and 4-methoxy-N-butylamphetamine (M-NBA) were incubated with microsomal preparations from cells expressing human CYP2D6 to determine whether the enzyme was capable of catalyzing the direct ring oxidation of all substrates; the N-dealkylation of NEA, NBA, M-NEA and M-NBA; and the O-demethylation of M-AM, M-NEA and M-NBA. None of the six compounds examined was N-dealkylated to any extent. The only metabolites produced from AM, NEA and NBA were the corresponding ring 4-hydroxylated compounds, and the rates of formation were low. All ring 4-methoxylated substrates were efficiently O-demethylated by CYP2D6 to their corresponding phenols. The size of the N-alkyl group influenced the rates of formation of these phenolamines. In contrast to reported findings with 2- and 3-methoxyamphetamines, none of the 4-methoxyamphetamines was ring-oxidized in the CYP2D6 enzyme system to 2- or 3-hydroxy-4-methoxyamphetamines or to dihydroxyamphetamines.

来源:Hazardous Substances Data Bank (HSDB)

代谢

p-甲氧基苯丙胺在狗和猴子尿液中的代谢物通过气液相色谱法作为三氟乙酰衍生物进行分离，并通过将这些衍生物的色谱和质谱行为与真实合成化合物的行为进行比较来鉴定。在狗和猴子中确定的三种新的代谢物是3-O-甲基-α-甲基多巴胺、4-羟基-3-甲氧基苄基甲基酮和4-羟基苄基甲基酮。在没有适当的标准品的情况下，第四种新的代谢物被暂时鉴定。

Metabolites of p-methoxyamphetamine in the urine of dogs and monkeys were separated by gas-liquid chromatography as their trifluoroacetyl derivatives, and identified by comparison of the chromatographic and mass spectrometric behavior of these derivatives with those of authentic synthetic compounds. The three new metabolites identified in both dogs and monkeys were 3-O-methyl-alpha-methyldopamine, 4-hydroxy-3-methoxybenzyl methyl ketone, and 4-hydroxybenzyl methyl ketone. A fourth new metabolite was tentatively identified in the absence of the appropriate reference standard.

来源:Hazardous Substances Data Bank (HSDB)

代谢

口服给药的4-甲氧基[14C]安非他命的尿排泄的定性和定量方面已经在老鼠、豚鼠和三名志愿者身上进行了研究，以确定不同物种和个体之间药物处置的变异。在豚鼠中，药物通过O-脱甲基作用被代谢为4-羟基安非他命，以游离形式（剂量的4%）和结合形式（73%）排出。没有检测到其他代谢物。老鼠通过O-脱烷基和侧链氧化代谢药物，产物为4-羟基安非他命（剂量的5%游离和60%结合）和1-(4'-甲氧基苯基)丙-2-酮肟（剂量的5%，游离和结合）。在人中，药物（剂量为5毫克）通过O-脱甲基和侧链氧化被代谢。在代谢物排泄的组成和数量方面观察到显著的个体间差异。两名受试者主要排泄4-羟基安非他命（游离和结合）以及较小量的1-(4'-甲氧基苯基)丙-2-酮肟和4-羟基去甲麻黄碱。然而，第三名受试者，之前已知表现出遗传决定的药物氧化缺陷，对4-甲氧基安非他命的O-脱烷基有缺陷，主要排泄产物是未改变的药物以及侧链氧化的产物，即1-(4'-甲氧基苯基)丙-2-酮肟、1-(4'-甲氧基苯基)丙-2-酮和4-甲氧基苯甲酸。

The qualitative and quantitative aspects of the urinary elimination of orally administered 4-methoxy[14C]amphetamine have been examined in the rat and guinea-pig and in three volunteer human subjects, to determine interspecies and interindividual variations in disposition of the drug. ... In the guinea-pig, the drug was metabolized by O-demethylation to give 4-hydroxyamphetamine, which was excreted free (4% dose) and conjugated (73%). No other metabolite was detected. The rat metabolizes the drug both by O-dealkylation and by side-chain oxidation, the products being 4-hydroxyamphetamine (5% of dose free and 60% conjugated) and 1-(4'-methoxyphenyl)propan-2-one oxime (5% dose, free and conjugated). In man the drug (dose 5 mg) is metabolized by O-demethylation and by side-chain oxidation. Marked intersubject variations were observed both in the array and quantitative aspects of metabolite excretion. Two subjects excreted mainly 4-hydroxyamphetamine (free and conjugated) together with smaller amounts of 1-(4'-methoxyphenyl)propan-2-one oxime and 4-hydroxynorephedrine. The third subject, however, who was previously known to exhibit a genetically determined defect in drug oxidation, was defective in O-dealkylation of 4-methoxyamphetamine, and the main excretion products were the unchanged drug together with products of side-chain oxidation, namely, 1-(4'-methoxyphenyl)propan-2-one oxime, 1-(4'-methoxyphenyl)propan-2-one and 4-methoxybenzoic acid. ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

在美国中西部最近发生了三起死亡事件，每位死者都认为自己摄入了甲氧基甲基苯丙胺（MDMA）。死者包括两名19岁和24岁的男性和一名18岁的女性，他们的死后血液中对甲氧基苯丙胺（PMA）的浓度分别为1.07、0.60和1.90毫克/升。PMA不是MDMA的污染物，在这些案例中都没有发现MDMA。PMA的主要代谢物是通过O-去甲基化产生4-羟基苯丙胺，这一反应由细胞色素P450 2D6催化。这种酶因基因多态性而闻名。那些具有“慢代谢型”表型的人可能会有更高的PMA血液峰值浓度。

... Three recent fatalities that occurred in the midwestern United States in which each of the decedents believed that they were ingesting methylenedioxymethamphetamine (MDMA) /were reported/. ... The deceased, two males ages 19 and 24 and a female age 18, had postmortem blood paramethoxyamphetamine (PMA) concentrations of 1.07, 0.60, and 1.90 mg/L, respectively. PMA is not a contaminant of MDMA, and no MDMA was found in any of these cases. The primary metabolite of PMA is produced by O-demethylation to 4-hydroxyamphetamine, a reaction catalyzed by cytochrome P450 2D6. This enzyme is noted to be genetically polymorphic. Those with the "slow metabolizer" phenotype may be likely to have higher peak blood concentrations of PMA.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

在当前研究中，研究者们使用微透析技术检查了在30摄氏度升高环境温度下，同时给予MDMA或对甲氧基苯丙胺（PMA）与莫罗贝米特的联合使用对纹状体5-HT外流的影响。样品每隔30分钟收集一次，持续4小时，并通过高效液相色谱电化学检测法（HPLC-ED）进行分析。记录了5-HT对体温和行为的影响。在大鼠接受生理盐水或20 mg/kg（腹腔注射）莫罗贝米特处理后，60分钟后给予10 mg/kg（腹腔注射）MDMA、10 mg/kg（腹腔注射）PMA或生理盐水。MDMA和PMA均显著增加了5-HT的外流（分别为370%的峰值和309%的峰值，P<0.05）。MDMA和PMA显著提高了体温（分别升高2.0摄氏度和2.1摄氏度，P<0.01）和药物相关行为（P<0.05）。当MDMA或PMA与莫罗贝米特联合使用时，5-HT外流显著增加（分别为850%的峰值，P<0.01和1450%的峰值，P<0.001），而且只有MDMA显示出体温的显著增加（升高5.0摄氏度，P<0.001）。行为活动没有额外的增加。当莫罗贝米特与MDMA联合使用时，记录到的体温持续升高显著高于单独使用MDMA时，而在我们之前在正常室温下的研究中并未观察到这种增加。作者的结果表明，在升高环境温度下，与PMA相比，MDMA与莫罗贝米特联合使用时对体温调节的不良影响风险更大。

... In the present study, using microdialysis, /investigators/ examined the effects of co-administration of MDMA or para-methoxyamphetamine (PMA) with moclobemide on striatal 5-HT outflow at the elevated ambient temperatures of 30 degrees C. Samples were collected every 30 min for 4 hr and analyzed by high-performance liquid chromatography assay with electrochemical detection (HPLC-ED). 5-HT-mediated effects on body temperature and behavior were also recorded. Rats were treated with either saline or 20 mg/kg (ip) moclobemide, followed by 10 mg/kg (ip) MDMA, 10 mg/kg (ip) PMA or saline 60 min later. Both MDMA and PMA produced significant increases in 5-HT outflow (370% peak and 309% peak, respectively, P<0.05). MDMA and PMA significantly increased body temperature (+2.0 degrees C and +2.1 degrees C, respectively, P<0.01) and drug-related behaviors (P<0.05). When MDMA or PMA was co-administered with moclobemide, additional significant increases were seen in 5-HT outflow (850% peak, P<0.01 and 1450% peak, P<0.001, respectively) and only MDMA showed additional significant increase in body temperature (+5.0 degrees C, P<0.001). No additional increases were seen in behavioral activity. When moclobemide was co-administered with MDMA, sustained increases in body temperature were recorded that were significantly higher than with MDMA alone and such increases were not observed in our previous study at normal room temperature. /The authors/ results suggest greater risk of MDMA-induced adverse effects on body temperature regulation, compared with PMA, when used in combination with moclobemide at elevated ambient temperatures.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

研究了十五种苯丙胺类物质与遗传多态性酶CYP2D6的相互作用。所有测试的苯基异丙胺都是人肝微粒体中CYP2D6的竞争性抑制剂。... 对CYP2D6催化的对甲氧基苯丙胺（PMA）的O-去甲基化进行了表征（Km = 59.2 +/- 22.4微M，Vmax = 29.3 +/- 16.6 nmol/mg/hr，N = 6个肝脏）。此反应在CYP2D6缺陷的肝微粒体中可以忽略不计，可以被奎尼丁/奎宁对映体对选择性地抑制，并且与右吗啡O-去甲基化（r = 0.975）共分离。亚甲二氧基甲基苯丙胺（MDMA）的抑制效果通过预孵育微粒体得到增强，这表明MDMA可能会与CYP2D6产生一个代谢物复合物。这些发现表明，苯丙胺类药物作为一个类别，可以作为CYP2D6的底物和/或抑制剂与之相互作用。它们的使用可能会导致与其他CYP2D6底物的药物发生代谢相互作用，而通过CYP2D6进行的遗传多态性氧化可能是它们滥用潜力和毒性个体间差异的来源。

The interaction of fifteen amphetamine analogs with the genetically polymorphic enzyme CYP2D6 was examined. All ... phenylisopropylamines tested were competitive inhibitors of CYP2D6 in human liver microsomes. ... O-Demethylation of p-methoxyamphetamine (PMA) by CYP2D6 was characterized (Km = 59.2 +/- 22.4 microM, and Vmax = 29.3 +/- 16.6 nmol/mg/hr, N = 6 livers). This reaction was negligible in CYP2D6-deficient liver microsomes, was inhibited stereoselectively by the quinidine/quinine enantiomer pair, and was cosegregated with dextromethorphan O-demethylation (r = 0.975). The inhibitory effect of methylenedioxymethamphetamine (MDMA) was enhanced by preincubation with microsomes, suggesting that MDMA may produce a metabolite complex with CYP2D6. These findings suggest that phenylisopropylamines as a class interact with CYP2D6 as substrates and/or inhibitors. Their use may cause metabolic interactions with other drugs that are CYP2D6 substrates, and the potential for polymorphic oxidation via CYP2D6 may be a source of interindividual variation in their abuse liability and toxicity.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

立即急救：确保已经进行了充分去污。如果患者停止呼吸，开始人工呼吸，最好使用需求阀复苏器、气囊面罩装置或口袋面罩，按训练进行操作。如有必要，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。如果发生呕吐，让患者向前倾或将其置于左侧（如果可能，头部向下）以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗救助。/毒物A和B/

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 if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the 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. /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

基本治疗：建立专利气道（如需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。观察呼吸不足的迹象，如有需要，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……。预防癫痫发作，如有必要，进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用0.9%的生理盐水（NS）连续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能吞咽、有强烈的呕吐反射且不流口水，则用水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干性无菌敷料覆盖皮肤烧伤……。/毒物A和B/

Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. 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 ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

高级治疗：对于昏迷、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。使用气囊面罩装置的正压通气技术可能有益。考虑使用药物治疗肺水肿……。对于严重的支气管痉挛，考虑给予β受体激动剂，如沙丁胺醇……。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%的生理盐水（NS）或乳酸钠林格氏液。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象……。用地西泮或劳拉西泮治疗癫痫……。使用丙美卡因氢氯化物协助眼部冲洗……。/毒物A和B/

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. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . 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 if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

口服给予的大鼠和豚鼠以及三名志愿者体内的4-甲氧基(14C)安非他命的尿排泄的定性和定量方面已经得到了研究，以确定不同物种和个体之间药物处置的变异。大鼠和豚鼠在24小时内主要以代谢物的形式排出了70-80%的给药剂量（6 mg/kg）。在豚鼠中，药物通过O-去甲基化代谢为4-羟基安非他命，以游离（4%剂量）和结合（73%）的形式排出。没有检测到其他代谢物。大鼠通过O-去烷基化和侧链氧化代谢药物，产物为4-羟基安非他命（5%剂量游离和60%结合）和1-(4'-甲氧基苯基)丙-2-酮肟（5%剂量，游离和结合）。在人中，药物（剂量5 mg）通过O-去甲基化和侧链氧化代谢。在代谢物排泄的定性和定量方面观察到了明显的个体间差异。两名受试者主要排泄4-羟基安非他命（游离和结合），以及少量的1-(4'-甲氧基苯基)丙-2-酮肟和4-羟基去甲麻黄碱。然而，第三名受试者，之前已知表现出遗传决定的药物氧化缺陷，4-甲氧基安非他命的O-去烷基化缺陷，主要排泄产物是未改变的药物以及侧链氧化的产物，即1-(4'-甲氧基苯基)丙-2-酮肟、1-(4'-甲氧基苯基)丙-2-酮和4-甲氧基苯甲酸。

The qualitative and quantitative aspects of the urinary elimination of orally administered 4-methoxy(14C)amphetamine have been examined in the rat and guinea-pig and in three volunteer human subjects, to determine interspecies and interindividual variations in disposition of the drug. Both rat and guinea-pig excreted 70-80% of the administered dose (6 mg/kg) in the urine within 24 hr mainly as metabolites. In the guinea pig, the drug was metabolized by O-demethylation to give 4-hydroxyamphetamine, which was excreted free (4% dose) and conjugated (73%). No other metabolite was detected. The rat metabolizes the drug both by O-dealkylation and by side-chain oxidation, the products being 4-hydroxyamphetamine (5% of dose free and 60% conjugated) and 1-(4'-methoxyphenyl)propan-2-one oxime (5% dose, free and conjugated). In man the drug (dose 5 mg) is metabolized by O-demethylation and by side-chain oxidation. Marked intersubject variations were observed both in the array and quantitative aspects of metabolite excretion. Two subjects excreted mainly 4-hydroxyamphetamine (free and conjugated) together with smaller amounts of 1-(4'-methoxyphenyl)propan-2-one oxime and 4-hydroxynorephedrine. The third subject, however, who was previously known to exhibit a genetically determined defect in drug oxidation, was defective in O-dealkylation of 4-methoxyamphetamine, and the main excretion products were the unchanged drug together with products of side-chain oxidation, namely, 1-(4'-methoxyphenyl)propan-2-one oxime, 1-(4'-methoxyphenyl)propan-2-one and 4-methoxybenzoic acid.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  1-(4-甲氧基苄基)乙胺 在 10% palladium on active carbon 吡啶 、 盐酸 、 Candida antarctica lipase B 、 aluminum oxide 、 氢氧化钾 、 氢气 、 铁粉 作用下， 以 甲醇 、 乙醇 、 二甲基亚砜 为溶剂， 反应 94.25h， 生成 福莫特罗
  参考文献：
  名称：

  An efficient enantioselective synthesis of (R,R)-formoterol, a potent bronchodilator, using lipases

  摘要：

  0The potent beta(2)-adrenergic receptor agonist formoterol (R,R)-1 has been obtained in enantiomerically pure form by a convenient chemoenzymatic approach by coupling of epoxide (R)-6 with the unprotected primary amine (R)-9. Both chiral precursors have been prepared by enantiodifferentiation processes involving Pseudomonas cepacia (lipase PS) and Candida antarctica lipase (CALB), respectively. For the resolution of amine 9, we have found that utilization of triethylamine as non-reactive base enhances the reaction rate and the enantioselectivity of the process. The key coupling reaction of (R)-6 and (R)-9 has been conducted through derivatization of the amine with the labile trimethylsilyl group, which liberates the amino group of the resulting amino alcohol (R,R)-11 upon column chromatography purification. In this way, the overall approach is shorter than others previously described. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(00)00238-x
• 作为产物：
  描述：

  茴香烯 在 间苯二甲腈 、 1,3,5-三苯基苯 、 氨 作用下， 以 水 、 乙腈 为溶剂， 以91%的产率得到1-(4-甲氧基苄基)乙胺
  参考文献：
  名称：

  苯乙烯衍生物与氨的光胺化反应合成苯乙胺部分

  摘要：

  在二氰基苯存在下，反式-1-芳基丙烯和7-甲氧基-1,2-二氢萘与氨光胺化，得到1-芳基-2-丙胺和2-氨基-6-甲氧基-1,2,3,4-四氢萘分别。通过添加1,3,5-三苯苯或间三联苯可提高胺化化合物的收率。

  DOI：

  10.1016/s0040-4039(00)60695-0
• 作为试剂：
  描述：

  (R)-α-methyl-N-(1,2,2-trimethylpropylidene)benzenemethanamine 、 1-(4-甲氧基苄基)乙胺 在 1-(4-甲氧基苄基)乙胺 作用下， 生成 (R)-3,3-二甲基-2-丁胺
  参考文献：
  名称：

  Amino-ethanol derivatives

  摘要：

  揭示了公式##STR1##的新化合物，其中R.sub.1 =H，线性或支链烷基基团，含有1至6个碳原子，含有3至6个碳原子的环烷基基团，烷基苯基基团，其中苯基可能被羟基或甲氧基取代；R.sub.2 =羟基，羟甲基 R.sub.3 =H，含有1-4个碳原子的烷基，甲酰基，碳基烷基，其中烷基基团含有1-3个碳原子，简单的碳酰胺基团或在氮原子上单取代或双取代的碳酰胺基团，含有1-3个碳原子的烷基基团。这些新化合物在治疗支气管疾病方面很有用。它们具有独特的特性，能够提供所需的支气管扩张效果，而不会引起任何伴随的心脏刺激。

  公开号：

  US04252824A1

文献信息

• Facile synthesis of controllable graphene-co-shelled reusable Ni/NiO nanoparticles and their application in the synthesis of amines under mild conditions
  作者：Jianguo Liu、Yuting Zhu、Chenguang Wang、Thishana Singh、Nan Wang、Qiying Liu、Zhibing Cui、Longlong Ma

  DOI：10.1039/d0gc02421j

  日期：——

  catalysts are stable and reusable and were successfully used for the synthesis of primary, secondary, tertiary, and N-methylamines (more than 62 examples). The reaction couples easily accessible carbonyl compounds (aldehydes and ketones) with ammonia, amines, and H2 under very mild industrially viable and scalable conditions (80 °C and 1 MPa H2 pressure, 4 h), offering cost-effective access to numerous functionalized

  化学合成中许多研究人员的主要目标是开发可回收和易于使用的催化剂。这些催化剂应优选由富含地球的金属制成，并具有用于合成药学上重要的化合物的能力。胺被列为特权化合物，并广泛用于精细和大宗化学工业以及制药和材料研究。在许多实验室和工业中，主要使用氨和H 2进行过渡金属催化的羰基化合物的还原胺化反应。但是，这些反应通常需要贵金属基催化剂或RANEY®镍，并且要求苛刻的反应条件，并且对所需产物的选择性较低。本文中，我们描述了一种简单且环保的方法，用于制备薄石墨烯球，该球体封装了使用柠檬酸镍作为前体的均匀Ni / NiO纳米合金催化剂（Ni / NiO @ C）。所得催化剂稳定且可重复使用，并且已成功用于伯，仲，叔和N-甲胺的合成（超过62个实例）。该反应在非常温和的工业可行且可扩展的条件下（80°C和1 MPa H 2）将易于获得的羰基化合物（醛和酮）与氨，胺和H 2偶联压力（4小时）后，可以经济高
• Vicinal Diamines as Smart Cosubstrates in the Transaminase-Catalyzed Asymmetric Amination of Ketones
  作者：Stefan E. Payer、Joerg H. Schrittwieser、Wolfgang Kroutil

  DOI：10.1002/ejoc.201700253

  日期：2017.5.3

  Transaminases (TAs) have recently been established as catalysts for the asymmetric, reductive amination of prochiral ketones. Depending on the ketone substrate and the amine donor (the cosubstrate), equilibrium constants may limit high conversions; thus, methods to overcome this limitation are required. Removal of the co-product from the reaction equilibrium through spontaneous, intramolecular reactions

  转氨酶 (TA) 最近已被确定为前手性酮不对称还原胺化的催化剂。根据酮底物和胺供体（共底物），平衡常数可能会限制高转化率；因此，需要克服这种限制的方法。通过自发的分子内反应从反应平衡中去除副产物为这个问题提供了成功的解决方案。因此，这些胺供体被命名为“智能共底物”。在这里，我们比较了各种双功能胺供体，包括作为潜在结构共底物基序的连二胺。在 TA 催化的 1,2-二胺脱氨基作用后，所得 α-氨基酮的自发二聚化和氧化得到杂芳族吡嗪。
• Enzymatic enantiomeric resolution of phenylethylamines structurally related to amphetamine
  作者：Lourdes Muñoz、Anna M. Rodriguez、Gloria Rosell、M. Pilar Bosch、Angel Guerrero

  DOI：10.1039/c1ob06251d

  日期：——

  prepared in good yields and excellent enantiomeric purity by enzymatic kinetic resolution using CAL-B and ethyl methoxyacetate as the acyl donor. In the case of the 4-hydroxyderivative of amphetamine (compound 4i), the S enantiomer racemized possibly in a dynamic kinetic resolution (DKR) under the enzymatic conditions used.

  几种苯乙胺的两种对映体，在结构上与 安非他命通过CAL-B和CAL-B的酶促动力学拆分，制备了高收率和优异的对映体纯度。 甲氧基乙酸乙酯作为酰基供体。在苯丙胺的4-羟基衍生物（化合物4i）的情况下，S对映异构体在所用的酶促条件下可能以动态动力学拆分（DKR）外消旋。
• Mild dynamic kinetic resolution of amines by coupled visible-light photoredox and enzyme catalysis
  作者：Qiong Yang、Fengqian Zhao、Na Zhang、Mingke Liu、Huanhuan Hu、Jingjie Zhang、Shaolin Zhou

  DOI：10.1039/c8cc07990k

  日期：——

  Herein, we described photoenzymatic dynamic kinetic resolution (DKR) of amines under mild conditions. The racemization of amines via a photoredox-mediated hydrogen atom transfer (HAT) protocol in conjunction with an enzyme catalyst to achieve the DKR of amines allows a variety of primary amines to be converted into a single enantiomer in high yield and with excellent enantioselectivity. Notably, this

  在这里，我们描述了在温和条件下胺的光酶动力学动力学拆分（DKR）。胺通过光氧化还原介导的氢原子转移（HAT）方案与酶催化剂的外消旋作用实现胺的DKR，可以将多种伯胺以高收率和出色的对映选择性转化为单一对映体。值得注意的是，该方案还可以扩展到具有高水平的非对映和对映选择性的1,4-二胺衍生物。
• An Ammonium-Formate-Driven Trienzymatic Cascade for ω-Transaminase-Catalyzed (<i>R</i>)-Selective Amination
  作者：Fei-Fei Chen、Yu-Hui Zhang、Zhi-Jun Zhang、Lei Liu、Jian-Ping Wu、Jian-He Xu、Gao-Wei Zheng

  DOI：10.1021/acs.joc.9b02445

  日期：2019.11.15

  (R)-Amination mediated by (R)-specific ω-transaminases generally requires costly d-alanine in excess to obtain the desired chiral amines in high yield. Herein, a one-pot, trienzymatic cascade comprising an (R)-specific ω-transaminase, an amine dehydrogenase, and a formate dehydrogenase was developed for the economical and eco-friendly synthesis of (R)-chiral amines. Using inexpensive ammonium formate as the

  由（R）-特异性ω-转氨酶介导的（R）-胺化通常需要过量的昂贵的d-丙氨酸以高产率获得所需的手性胺。本文中，开发了包含（R）-特异性ω-转氨酶，胺脱氢酶和甲酸酯脱氢酶的一锅三酶级联反应，以经济和环保地合成（R）-手性胺。使用廉价的甲酸铵作为唯一的牺牲剂，已建立的级联系统实现了各种酮的高效ω-转氨酶介导的（R）胺化，具有高转化率和优异的ee（> 99％）；水和二氧化碳是唯一的废物。

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