(1R,2R)-2-苯基环丙烷甲酰胺 | 939-88-8

• 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: (1R,2R)-2-苯基环丙烷甲酰胺
• 中文别名: 反式-2-苯基环丙烷-1-羧酰胺
• 英文名称: rac-(1R,2R)-2-phenylcyclopropanecarboxamide
• 英文别名: trans-2-phenylcyclopropanecarboxamide；(+/-)-trans-2-phenyl-cyclopropane-carboxylic acid-(1)-amide；(+/-)-trans-2-Phenyl-cyclopropan-carbonsaeure-(1)-amid；trans-(+/-)-2-phenyl-cyclopropanecarboxylic acid amide；trans-1-Phenyl-cyclopropan-carbonsaeure-(2)-amid；trans-2-Phenyl-cyclopropan-carbonsaeure-(1)-amid；(1S,2S)-2-phenylcyclopropane-1-carboxamide
• CAS: 939-88-8；1009-39-8；4659-85-2；58641-87-5
• 化学式: C₁₀H₁₁NO
• 分子量: 161.203
• InChiKey: IOWKRFFHXWDUIS-BDAKNGLRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  43.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (1R,2R)-2-苯基环丙烷甲酰胺 在 氯化亚砜 作用下， 生成 trans-2-phenylcyclopropanecarbonitrile
  参考文献：
  名称：

  Horak,M. et al., Collection of Czechoslovak Chemical Communications, 1963, vol. 28, p. 2280 - 2293

  摘要：

  DOI：
• 作为产物：
  描述：

  trans-2-phenyl-1-cyclopropanecarbonyl chloride 在 氨 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 生成 (1R,2R)-2-苯基环丙烷甲酰胺
  参考文献：
  名称：

  Selective 5-Hydroxytryptamine 2C Receptor Agonists Derived from the Lead Compound Tranylcypromine: Identification of Drugs with Antidepressant-Like Action

  摘要：

  We report here the design, synthesis, and pharmacological properties of a series of compounds related to tranylcypromine (9), which itself was discovered as a lead compound in a high-throughput screening campaign. Starting from 9, which shows modest activity as a 5-HT2C agonist, a series of 1-aminomethyl-2-phenylcyclopropanes was investigated as 5-HT2C agonists through iterative structural modifications. Key pharmacophore feature of this new class of ligands is a 2-aminomethyl-trans-cyclopropyl side chain attached to a substituted benzene ring. Among the tested compounds, several were potent and efficacious 5-HT2C receptor agonists with selectivity over both 5-HT2A and 5-HT2B receptors in functional assays. The most promising compound is 37, with 120- and 14-fold selectivity over 5-HT2A and 5-HT2B, respectively (EC50 = 585, 65, and 4.8 nM at the 2A, 2B, and 2C subtypes, respectively). In animal studies, compound 37 (10-60 mg/kg) decreased immobility time in the mouse forced swim test.

  DOI：

  10.1021/jm801354e

文献信息

• Highly Chemoselective Reduction of Amides (Primary, Secondary, Tertiary) to Alcohols using SmI₂/Amine/H₂O under Mild Conditions
  作者：Michal Szostak、Malcolm Spain、Andrew J. Eberhart、David J. Procter

  DOI：10.1021/ja412578t

  日期：2014.2.12

  Highly chemoselective direct reduction of primary, secondary, and tertiary amides to alcohols using SmI2/amine/H2O is reported. The reaction proceeds with C–N bond cleavage in the carbinolamine intermediate, shows excellent functional group tolerance, and delivers the alcohol products in very high yields. The expected C–O cleavage products are not formed under the reaction conditions. The observed

  据报道，使用 SmI2/胺/H2O 将伯、仲和叔酰胺高度化学选择性地直接还原为醇。该反应在甲醇胺中间体中进行 C-N 键断裂，显示出优异的官能团耐受性，并以非常高的产率提供醇产物。在反应条件下不会形成预期的 C-O 裂解产物。观察到的反应性与由 nX → π*C=O (X = O, N) 共轭产生的极性羰基的亲电性相反。机理研究表明，在四面体中间体中，Sm 与羰基和路易斯碱性氮的配位促进了电子转移并控制了 C-N/C-O 裂解的选择性。尤其，
• Mechanism of SmI₂/Amine/H₂O-Promoted Chemoselective Reductions of Carboxylic Acid Derivatives (Esters, Acids, and Amides) to Alcohols
  作者：Michal Szostak、Malcolm Spain、Andrew J. Eberhart、David J. Procter

  DOI：10.1021/jo5018525

  日期：2014.12.19

  Samarium(II) iodide–water–amine reagents have emerged as some of the most powerful reagents (E° = −2.8 V) for the reduction of unactivated carboxylic acid derivatives to primary alcohols under single electron transfer conditions, a transformation that had been considered to lie outside the scope of the classic SmI2 reductant for more than 30 years. In this article, we present a detailed mechanistic

  single（II）碘化物-水-胺试剂已成为一些最强大的试剂（E °= -2.8 V），可在单电子转移条件下将未活化的羧酸衍生物还原为伯醇。超过经典SmI 2还原剂的使用范围已超过30年。在本文中，我们提供了使用SmI 2还原未活化的酯，羧酸和酰胺的详细机理研究-水-胺试剂，我们在其中比较三个官能团的反应性。已使用以下方法研究了该机理：（i）动力学，（ii）反应性，（iii）自由基钟和（iv）同位素标记实验。动力学数据表明，对于三个官能团，所有反应组分（SmI 2，胺，水）都包含在速率方程中，并且碱辅助的水去质子化促进了电子转移的速率。值得注意的是，本文给出的机理细节表明SmI 2之间的复合，水和胺类可产生一类结构多样，热力学强大的还原剂，可将电子有效转移到各种羧酸衍生物中。这些观察结果将对涉及Sm（II）还原酮基还原反应的新工艺的设计和优化产生重要影响。
• A novel approach to enantiopure cyclopropane compounds from biotransformation of nitrilesElectronic supplementary information (ESI) available: preparation of racemic nitrile, amides and acids; spectroscopic data of racemic nitriles; biotransformation of racemic amides; chiral HPLC analyses of nitriles, amides, acids and amines. See http://www.rsc.org/suppdata/nj/b2/b200110a/
  作者：Mei-Xiang Wang、Guo-Qiang Feng

  DOI：10.1039/b200110a

  日期：2002.10.30

  Rhodococcus sp. AJ270, a powerful and versatile nitrile hydratase/amidase containing microbial whole-cell system, catalyzed the enantioselective hydrolysis of both racemic trans- and cis-2-arylcyclopropanecarbonitriles to afford the corresponding amides and acids with enantiomeric excesses as high as >99%. The reaction rate and enantioselectivity observed for both nitrile hydratase and amidase were also strongly dependent upon the nature of the substituent and substitution pattern on the benzene ring of the substrates. The application of and the advantages of biotransformation of nitriles were demonstrated by preparing (1S,2R)-2-phenylcyclopropylamine and (1R,2R)-2-phenylcyclopropylmethylamine through facile and straightforward chemical manipulations of (1S,2S)-2-phenylcyclopropanecarboxylic acid and (1R,2R)-2-phenylcyclopropanecarboxamide, respectively.

  Rhodococcus sp. AJ270 是一种功能强大、用途广泛的腈水解酶/酰胺酶，含有微生物全细胞系统，可催化外消旋反式和顺式-2-芳基环丙烷甲腈的对映选择性水解，生成相应的酰胺和酸，对映过量高达 99%以上。腈水解酶和酰胺酶的反应速率和对映体选择性还与底物苯环上取代基的性质和取代模式密切相关。通过对(1S,2S)-2-苯基环丙烷羧酸和(1R,2R)-2-苯基环丙烷甲酰胺进行简单直接的化学处理，分别制备出(1S,2R)-2-苯基环丙胺和(1R,2R)-2-苯基环丙基甲胺，证明了腈类生物转化的应用和优势。
• Reactions of amines. XVIII. Oxidative rearrangement of amides with lead tetraacetate
  作者：Henry E. Baumgarten、Howard L. Smith、Andris Staklis

  DOI：10.1021/jo00912a019

  日期：1975.11
• Inhibition of the mammalian .beta.-lactamase renal dipeptidase (dehydropeptidase-I) by Z-2-(acylamino)-3-substituted-propenoic acids
  作者：Donald W. Graham、Wallace T. Ashton、Louis Barash、Jeannette E. Brown、Ronald D. Brown、Laura F. Canning、Anna Chen、James P. Springer、Edward F. Rogers

  DOI：10.1021/jm00389a018

  日期：1987.6

  The title enzyme deactivates the potent carbapenem antibiotic imipenem in the kidney, producing low antibiotic levels in the urinary tract. A series of (Z)-2-(acylamino)-3-substituted-propenoic acids (3) are specific, competitive inhibitors of the enzyme capable of increasing the urinary concentration of imipenem in vivo. Many of the compounds were prepared in one step from an alpha-keto acid and a primary amide. The optimum R2 groups are 2,2-dimethyl, -dichloro, and -dibromocyclopropyl. With R2 = 2,2-dimethylcyclopropyl (DMCP), a wide variety of R3 groups including alkyl, oxa- and thiaalkyl, and alkyl groups containing acidic, basic, and neutral substituents give effective inhibitors with Ki values of 0.02-1 microM and a range of pharmacokinetic properties. By resolution of enantiomers and X-ray crystallography, the enzyme-inhibitory activity of the DMCP group was found to reside with the 1S isomer. The cysteinyl compound 176 (cilastatin, MK-0791) has the desired pharmacological properties and has been chosen for combination with imipenem.