[(1R)-1-氰基-2-苯基乙基]氨基甲酸叔丁酯 | 400652-45-1

• 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: [(1R)-1-氰基-2-苯基乙基]氨基甲酸叔丁酯
• 英文名称: (R)-tert-butyl (1-cyano-2-phenylethyl)carbamate
• 英文别名: tert-butyl N-[(1R)-1-cyano-2-phenylethyl]carbamate
• CAS: 400652-45-1
• 化学式: C₁₄H₁₈N₂O₂
• 分子量: 246.309
• InChiKey: PMCZSKSPRUQIOF-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  62.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [(1R)-1-氰基-2-苯基乙基]氨基甲酸叔丁酯 在 羟胺 作用下， 以 乙醇 、 水 为溶剂， 反应 18.0h， 生成 (R)-[1-(N-hydroxycarbamimidoyl)-2-phenylethyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  由旋光性α-氨基酸制备旋光性α-氨基4 H- [1,2,4]恶二唑-5-酮

  摘要：

  在五个合成步骤中，由旋光性α-氨基酸制备旋光性α-氨基4 H- [1,2,4]恶二唑-5-酮（恶二唑酮）。恶二唑酮部分用作羧酸的生物立体替代物。描述了将α-氨基恶二唑酮掺入代表性的二肽模拟物中。

  DOI：

  10.1016/j.tet.2009.09.045
• 作为产物：
  描述：

  Boc-D-苯丙氨酸 在 1-羟基苯并三唑 、 1,2-二氯乙烷 、 三乙胺 、 三氟乙酸酐 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.5h， 生成 [(1R)-1-氰基-2-苯基乙基]氨基甲酸叔丁酯
  参考文献：
  名称：

  Synthesis and structure-activity relationship of nitrile-based cruzain inhibitors incorporating a trifluoroethylamine-based P2 amide replacement

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2019.115083

文献信息

• One-pot conversion of aldehydes to nitriles mediated by TiCl 4
  作者：Antonella Leggio、Emilia Lucia Belsito、Sonia Gallo、Angelo Liguori

  DOI：10.1016/j.tetlet.2017.03.007

  日期：2017.4

  synthesis of nitriles from the corresponding aliphatic and aromatic aldehydes has been developed. The titanium tetrachloride assisted reaction was conducted in pyridine under mild conditions using various types of aldehyde precursors and gave the corresponding nitriles in excellent yields. The application of the adopted protocol to isolated aldoxime intermediates provided the corresponding nitriles with

  已经开发了由相应的脂族和芳族醛简单且方便的一锅合成腈。四氯化钛辅助反应是在吡啶中于温和条件下使用各种类型的醛前体进行的，并以优异的收率得到相应的腈。将所采用的方案应用于分离的醛肟中间体，可以为相应的腈提供与一锅法可比的产率。
• Phase Transfer Catalyzed Enantioselective Strecker Reactions of α-Amido Sulfones with Cyanohydrins
  作者：Raquel P. Herrera、Valentina Sgarzani、Luca Bernardi、Francesco Fini、Daniel Pettersen、Alfredo Ricci

  DOI：10.1021/jo061566u

  日期：2006.12.1

  A study into the use of a chiral phase-transfer catalyst in conjunction with acetone cyanohydrin to effect the enantioselective formation of α-amino nitriles from α-amido sulfones is described. This novel catalytic asymmetric Strecker reaction is analyzed with regard to the possible mechanistic basis.

  描述了将手性相转移催化剂与丙酮氰醇结合使用以实现由α-酰胺基砜对映选择性形成α-氨基腈的研究。就可能的机理基础分析了这种新颖的催化不对称斯特雷克反应。
• Synthesis of Enantiomerically Pure <i>N</i>-Acyl Amino Nitriles via Catalytic Dehydration of Oximes and Application in a <i>de Novo</i> Synthesis of Vildagliptin
  作者：Philipp Rommelmann、Tobias Betke、Harald Gröger

  DOI：10.1021/acs.oprd.7b00169

  日期：2017.10.20

  which are readily available from N-acyl l- or d-α-amino aldehydes through condensation with hydroxylamine, has been developed. The desired products were obtained with high conversion and in enantiomeric excesses of 97–99% ee. Furthermore, this method has been applied in the synthesis of an N-chloroacetylated 2-cyanopyrrolidine, which represents a building block for the synthesis of Vildagliptin.

  一种基于对醛肟的Cu（OAc）2催化脱水的对映异构体高度富集的N-酰基氨基腈的替代路线，该路线很容易从N-酰基l-或d -α-氨基醛中通过与羟胺缩合而获得。发达。所需的产物以高转化率和对映体过量97–99％ee获得。此外，该方法已经应用于N-氯乙酰化的2-氰基吡咯烷的合成，其代表了维格列汀的合成的基础。
• METHOD FOR PRODUCING CHIRAL AMINONITRILES
  申请人：UNIVERSITÄT BIELEFELD

  公开号：US20190185428A1

  公开（公告）日：2019-06-20

  The invention relates to a method for preparing an N-acyl- or N-sulfonyl-α-aminonitrile, comprising the following steps: a) condensation of an N-acyl- or N-sulfonyl-α-aminoaldehyde with hydroxylamine to give an aldoxime, and b) dehydration of the aldoxime obtained in step a) to give an N-acyl- or N-sulfonyl-α-aminonitrile. In an advantageous manner, the absolute configuration can be retained in the conversion to the N-acyl- or N-sulfonyl-α-aminonitrile.

  该发明涉及一种制备N-酰基或N-磺酰基-α-氨基腈的方法，包括以下步骤：a)将N-酰基或N-磺酰基-α-氨基醛与羟胺缩合，得到醛肟；b)将步骤a)得到的醛肟脱水，得到N-酰基或N-磺酰基-α-氨基腈。优点是，在转化为N-酰基或N-磺酰基-α-氨基腈时，可以保留绝对构型。
• 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.