(S)-tert-butyl 2-hexanamido-3-methylbutanoate | 1418206-60-6

• 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
• 英文名称: (S)-tert-butyl 2-hexanamido-3-methylbutanoate
• 英文别名: tert-butyl (2S)-2-(hexanoylamino)-3-methylbutanoate
• CAS: 1418206-60-6
• 化学式: C₁₅H₂₉NO₃
• mdl: MFCD25013400
• 分子量: 271.4
• InChiKey: NVXHLYRVFXNJGK-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  19
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.866
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-tert-butyl 2-hexanamido-3-methylbutanoate 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 生成 methyl (2S)-5-(dimethylamino)-2-[[(2S)-2-(hexanoylamino)-3-methylbutanoyl]amino]-5-oxopentanoate
  参考文献：
  名称：

  Enzyme Inhibition by Hydroamination: Design and Mechanism of a Hybrid Carmaphycin-Syringolin Enone Proteasome Inhibitor

  摘要：

  Hydroamination reactions involving the addition of an amine to an inactivated alkene are entropically prohibited and require strong chemical catalysts. While this synthetic process is efficient at generating substituted amines, there is no equivalent in small molecule-mediated enzyme inhibition. We report an unusual mechanism of proteasome inhibition that involves a hydroamination reaction of alkene derivatives of the epoxyketone natural product carmaphycin. We show that the carmaphycin enone first forms a hemiketal intermediate with the catalytic Thr1 residue of the proteasome before cyclization by an unanticipated intramolecular alkene hydroamination reaction, resulting in a stable six-membered morpholine ring. The carmaphycin enone electrophile, which does not undergo a 1,4-Michael addition as previously observed with vinyl sulfone and alpha,beta-unsaturated amide-based inhibitors, is partially reversible and gives insight into the design of proteasome inhibitors for cancer chemotherapy.

  DOI：

  10.1016/j.chembiol.2014.04.010
• 作为产物：
  描述：

  L-缬氨酸叔丁酯盐酸盐 、 己酰氯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 7.0h， 以99%的产率得到(S)-tert-butyl 2-hexanamido-3-methylbutanoate
  参考文献：
  名称：

  [EN] METHODS OF PROMOTING NEURON GROWTH
  [FR] PROCÉDÉS DE FAVORISATION DE LA CROISSANCE DE NEURONES

  摘要：

  本发明提供了通过部分或完全抑制几丁质蛋白酶样蛋白酶或蛋白酶体活性来治疗、预防、逆转和/或改善神经退行性疾病或症状的方法。

  公开号：

  WO2013009923A1

文献信息

• Amide Formation in One Pot from Carboxylic Acids and Amines via Carboxyl and Sulfinyl Mixed Anhydrides
  作者：Bartosz K. Zambroń、Srinivas R. Dubbaka、Dean Marković、Elena Moreno-Clavijo、Pierre Vogel

  DOI：10.1021/ol401053y

  日期：2013.5.17

  An efficient method has been developed for the preparation of yet unknown acyclic mixed anhydrides of carboxylic and sulfinic acids. Sterically hindered 2-methylbut-3-ene-2-sulfinyl carboxylates add primary and secondary amines preferentially onto the carbonyl moieties realizing a new method for the one-pot preparation of carboxamides. It uses 1:1 mixtures of carboxylic acids and amines without a base

  已经开发了一种有效的方法来制备未知的羧酸和亚磺酸的无环混合酸酐。受位阻的2-甲基丁-3-烯-2-亚磺酰基羧酸酯优先将伯胺和仲胺添加到羰基部分上，实现了一种一锅法制备羧酰胺的新方法。它使用不带碱的1：1羧酸和胺混合物，不需要过量的试剂，仅释放挥发性副产物。通过应用该方法，可以在溶液中制备受保护的二肽和三肽，而没有差向异构化。
• [EN] METHODS OF PROMOTING NEURON GROWTH<br/>[FR] PROCÉDÉS DE FAVORISATION DE LA CROISSANCE DE NEURONES
  申请人：UNIV CREIGHTON

  公开号：WO2013009923A1

  公开（公告）日：2013-01-17

  The present invention provides methods to treat, prevent, reverse and/or ameliorate a neurodegenerative disease or condition by partially or completely inhibiting a chymotrypsin-like protease or a proteasome activity.

  本发明提供了通过部分或完全抑制几丁质蛋白酶样蛋白酶或蛋白酶体活性来治疗、预防、逆转和/或改善神经退行性疾病或症状的方法。
• Enzyme Inhibition by Hydroamination: Design and Mechanism of a Hybrid Carmaphycin-Syringolin Enone Proteasome Inhibitor
  作者：Daniela B.B. Trivella、Alban R. Pereira、Martin L. Stein、Yusuke Kasai、Tara Byrum、Frederick A. Valeriote、Dean J. Tantillo、Michael Groll、William H. Gerwick、Bradley S. Moore

  DOI：10.1016/j.chembiol.2014.04.010

  日期：2014.6

  Hydroamination reactions involving the addition of an amine to an inactivated alkene are entropically prohibited and require strong chemical catalysts. While this synthetic process is efficient at generating substituted amines, there is no equivalent in small molecule-mediated enzyme inhibition. We report an unusual mechanism of proteasome inhibition that involves a hydroamination reaction of alkene derivatives of the epoxyketone natural product carmaphycin. We show that the carmaphycin enone first forms a hemiketal intermediate with the catalytic Thr1 residue of the proteasome before cyclization by an unanticipated intramolecular alkene hydroamination reaction, resulting in a stable six-membered morpholine ring. The carmaphycin enone electrophile, which does not undergo a 1,4-Michael addition as previously observed with vinyl sulfone and alpha,beta-unsaturated amide-based inhibitors, is partially reversible and gives insight into the design of proteasome inhibitors for cancer chemotherapy.