2-amino-3-phenylpropanenitrile | 159517-27-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-amino-3-phenylpropanenitrile
• 英文别名: (R)-2-amino-3-phenylpropanenitrile；D-phenylalaninonitrile；(R)-2-amino-3-phenylpropionitrile；(2R)-2-Amino-3-phenylpropanenitrile
• CAS: 159517-27-8
• 化学式: C₉H₁₀N₂
• 分子量: 146.192
• InChiKey: AVXNAHRDJXOJHT-SECBINFHSA-N

物化性质

• 沸点：
  285.2±28.0 °C(Predicted)
• 密度：
  1.073±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-amino-3-phenylpropanenitrile 在 ZIRCONIUM(IV) TERT-BUTOXIDE 作用下， 以 甲苯 为溶剂， 反应 24.0h， 生成 2-amino-3-phenylpropanenitrile
  参考文献：
  名称：

  [EN] PROCESS FOR THE RACEMISATION OF ENANTIOMERICALLY ENRICHED ALPHA-AMINO NITRILES
  [FR] METHODE DE RACEMISATION D'ALPHA-AMINONITRILES ENRICHIS D'ENANTIOMERES

  摘要：

  对富集对映体的α-氨基腈进行消旋的过程特点在于将富集对映体的α-氨基腈与路易斯酸催化剂接触。最好使用无水溶剂。路易斯酸催化剂最好包括从周期表（CAS版本）的主族元素IA-IVA、过渡金属和镧系元素中选择的金属，特别是铝、钛、锆或镧系元素。例如，催化剂具有一般结构MnXpSqLr，最好从铝烷氧化物、铝烷基、镧系烷氧化物和镧系烷基中选择。消旋可以与分离过程结合进行，例如与酶法或结晶诱导的分离过程结合，最好是原位的，例如在结晶诱导的不对称转化过程中原位进行。

  公开号：

  WO2004046088A1
• 作为产物：
  描述：

  (2R,3S)-2-cyano-3-phenylaziridine 在 palladium on activated charcoal 氢气 作用下， 生成 2-amino-3-phenylpropanenitrile
  参考文献：
  名称：

  手性3-乙酰氧基氨基-3,4-二氢喹唑啉-4-酮在烯烃的叠氮化中的试剂控制的非对映选择性：1'-（叔丁基二甲基甲硅烷氧基）乙基为喹唑啉酮上的手性2-取代基

  摘要：

  3-乙酰氧基氨基喹唑啉酮3中的t BuMe 2 SiOCH （Me）CN单元内的构象偏爱导致H，Me和OSiMe 2 t Bu在过渡态的确定位置偏爱，因此与它的反应具有非对映选择性。 β-三甲基甲硅烷基苯乙烯4得到氮丙啶5。

  DOI：

  10.1016/0040-4039(96)01055-6

文献信息

• Regioselective Hydration and Deprotection of Chiral, Dissymmetric Iminodinitriles in the Scope of an Asymmetric Strecker Strategy
  作者：Jean-Christophe Rossi、Marc Marull、Laurent Boiteau、Jacques Taillades

  DOI：10.1002/ejoc.200600294

  日期：2007.2

  alpha-aminonitrile. In addition to the use of quite simple, cheap cyclic ketones (e.g. carvone derivatives) as chiral auxiliaries, another great advantage of this strategy is that step (iii) enables the recovery of the chiral ketone and hence its reuse. While our previous investigations on step (iii) under various conditions, either preceded or followed by the hydration of the secondary nitrile group

  式 RCH(CN)–NH–C(CN)R'R″（被视为 N 保护的 α-氨基腈）的不对称亚氨基二腈 (DIDN) 的受控选择性分解是先前原始不对称 Strecker 策略的关键问题我们概述了氨基酸的对映选择性合成。该策略源自 Harada 的工作，涉及 (i) 手性酮 R'R″CO 与 NH3 和 HCN 的立体选择性 Strecker 缩合，然后是 (ii) 与醛 RCHO 和 HCN 的立体选择性 Strecker 缩合，然后（ iii) DIDN 中间体的区域选择性逆向 Strecker 分解以释放目标 α-氨基腈。除了使用非常简单、廉价的环酮（例如香芹酮衍生物）作为手性助剂外，该策略的另一个巨大优势是步骤 (iii) 能够回收手性酮并因此对其进行再利用。虽然我们之前在各种条件下对步骤 (iii) 的研究，无论是在仲腈基团 RH(CN)- 水合成酰胺之前还是之后，都表明选择性不足，但我
• Process for the preparation of enantiomerically enriched compounds
  申请人：Dassen Nicolaas Bernardus Hedricus

  公开号：US20050215822A1

  公开（公告）日：2005-09-29

  Process for the preparation of enantiomerically enriched amino aldehydes and amino alcohols, wherein a corresponding enantiomerically enriched amino nitrile is subjected to hydrogenation in the presence of hydrogen, a hydrogenation catalyst, preferably a Pd-catalyst and a mineral acid. For the preparation of an amino aldehyde hydrogen preferably is present at a hydrogen-pressure between 0.1 and 2 MPa, in particular between 0.5 and 1 MPa. The amino aldehyde preferably is isolated in the form of a chemically and configurationally stable derivative. For the preparation of an amino alcohol, preferably at least during part of the hydrogenation hydrogen is present at a hydrogen-pressure between 2 and 10 MPa, in particular between 4 and 6 MPa. In a preferred embodiment the hydrogen-pressure initially is between 0.5 and 2 MPa and subsequently, after most of the nitrile starting material is converted, the hydrogen pressure is increased to a value between 2 and 10 MPa. The enantiomerically enriched nitrile starting material may a.o. be prepared by enzymatic resolution, classical resolution, resolution via preferential crystallization, diastereomeric synthesis, catalytic asymmetric synthesis or dehydratation of amino acid amides.

  制备对映富集的氨基醛和氨基醇的过程，其中相应的对映富集的氨基腈在氢气、氢化催化剂，优选为钯催化剂和矿酸存在下进行氢化。制备氨基醛时，氢气压力最好在0.1至2兆帕之间，特别是在0.5至1兆帕之间。氨基醛最好以化学和构型稳定的衍生物形式分离。制备氨基醇时，最好在氢气压力在2至10兆帕之间，特别是在4至6兆帕之间的部分氢化过程中存在氢气。在一种优选实施方式中，氢气压力最初在0.5至2兆帕之间，随后，在大部分腈起始物质转化后，将氢气压力增加到2至10兆帕之间。对映富集的腈起始物质可以通过酶解、经典分离、通过优先结晶分离、对映异构合成、催化不对称合成或氨基酸酰胺脱水反应等方法制备。
• Process for the racemisation of enantiomerically enriched alpha-amino nitriles
  申请人：Verzijl Karl Maria Gerardus

  公开号：US20060142610A1

  公开（公告）日：2006-06-29

  Process for the racemisation of an enantiomerically enriched α-amino nitrile characterized in that the enantiomerically enriched α-amino nitrile is contacted with a lewis acid catalyst. Preferably an aprotic solvent is used. The lewis acid catalyst preferably comprises a metal chosen from main group elements IA-IVA of the Periodic Table (CAS version), the transition metals and the lanthanides, in particular Al, Ti, Zr, or lanthanides. The catalsyt for example has the general structure MnXpSqLr, and preferably is chosen from the group of aluminum alkoxides, aluminum alkyls, lanthanide alkoxydes and lanthanocenes. The racemisation may be performed in combination with a resolution process, for instance in combination with an enzymatic or a crystallization induced resolution process, preferably in situ, for instance in situ in a crystallization induced asymmetric transformation process.

  对映体富集的 α-氨基腈的消旋化工艺，其特征在于对映体富集的 α-氨基腈与路易斯酸催化剂接触。最好使用无相溶剂。路易斯酸催化剂最好由选自元素周期表（CAS 版）主族元素 IA-IVA、过渡金属和镧系元素，特别是 Al、Ti、Zr 或镧系元素的金属组成。例如，催化剂的一般结构为 MnXpSqLr，最好选自铝烷氧基化物、铝烷基、镧烷氧基化物和镧烯类。外消旋化可以结合解析过程进行，例如结合酶解或结晶诱导解析过程，最好是原位解析， 例如在结晶诱导不对称转化过程中原位解析。
• Synthesis and structure-activity relationship of nitrile-based cruzain inhibitors incorporating a trifluoroethylamine-based P2 amide replacement
  作者：Juliana C. Gomes、Lorenzo Cianni、Jean Ribeiro、Fernanda dos Reis Rocho、Samelyn da Costa Martins Silva、Pedro Henrique Jatai Batista、Carolina Borsoi Moraes、Caio Haddad Franco、Lucio H.G. Freitas-Junior、Peter W. Kenny、Andrei Leitão、Antonio C.B. Burtoloso、Daniela de Vita、Carlos A. Montanari

  DOI：10.1016/j.bmc.2019.115083

  日期：2019.11

  The structure-activity relationship for nitrile-based cruzain inhibitors incorporating a P2 amide replacement based on trifluoroethylamine was explored by deconstruction of a published series of inhibitors. It was demonstrated that the P3 biphenyl substituent present in the published inhibitor structures could be truncated to phenyl with only a small loss of affinity. The effects of inverting the configuration of the P2 amide replacement and linking a benzyl substituent at P1 were observed to be strongly nonadditive. We show that plotting affinity against molecular size provides a means to visualize both the molecular size efficiency of structural transformations and the nonadditivity in the structure-activity relationship. We also show how the relationship between affinity and lipophilicity, measured by high-performance liquid chromatography with an immobilized artificial membrane stationary phase, may be used to normalize affinity with respect to lipophilicity.
• Optimization strategy of single-digit nanomolar cross-class inhibitors of mammalian and protozoa cysteine proteases
  作者：Lorenzo Cianni、Fernanda dos Reis Rocho、Fabiana Rosini、Vinícius Bonatto、Jean F.R. Ribeiro、Jerônimo Lameira、Andrei Leitão、Anwar Shamim、Carlos A. Montanari

  DOI：10.1016/j.bioorg.2020.104039

  日期：2020.8

  Cysteine proteases (CPs) are involved in a myriad of actions that include not only protein degradation, but also play an essential biological role in infectious and systemic diseases such as cancer. CPs also act as biomarkers and can be reached by active-based probes for diagnostic and mechanistic purposes that are critical in health and disease. In this paper, we present the modulation of a CP panel of parasites and mammals (Trypanosoma cruzi cruzain, LmCPB, CatK, CatL and CatS), whose inhibition by nitrile peptidomimetics allowed the identification of specificity and selectivity for a given CP. The activity cliffs identified at the CP inhibition level are useful for retrieving trends through multiple structure-activity relationships. For two of the cruzain inhibitors (10g and 4e), both enthalpy and entropy are favourable to Gibbs binding energy, thus overcoming enthalpy-entropy compensation (EEC). Group contribution of individual molecular modification through changes in enthalpy and entropy results in a separate partition on the relative differences of Gibbs binding energy (Delta Delta G). Overall, this study highlights the role of CPs in polypharmacology and multi-target screening, which represents an imperative trend in the actual drug discovery effort.