(S)-benzyl tert-butyl (6-hydroxyhexane-1,5-diyl)dicarbamate | 122477-82-1

• 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: (S)-benzyl tert-butyl (6-hydroxyhexane-1,5-diyl)dicarbamate
• 英文别名: (S)-(5-Benzyloxycarbonylamino-6-hydroxy-hexyl)-carbamic acid tert-butyl ester；benzyl N-[(2S)-1-hydroxy-6-[(2-methylpropan-2-yl)oxycarbonylamino]hexan-2-yl]carbamate
• CAS: 122477-82-1
• 化学式: C₁₉H₃₀N₂O₅
• 分子量: 366.458
• InChiKey: VHMMLCXHSMDTHS-INIZCTEOSA-N

物化性质

• 沸点：
  551.4±50.0 °C(Predicted)
• 密度：
  1.122±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  26
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  96.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-benzyl tert-butyl (6-hydroxyhexane-1,5-diyl)dicarbamate 在 palladium on activated charcoal benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 二乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.5h， 生成 N-acetyl-3[2-(oxocyclohexyl)thio]-alanine-Val-Lys(Boc)-CH2OH
  参考文献：
  名称：

  Aspartic Protease Inhibitors Designed from Computer-Generated Templates Bind As Predicted

  摘要：

  [GRAPHICS]Novel tripeptide-derived peptidomimetics 1, 7ab, and 8ab, inspired by templates generated by the structure generating program GrowMol, were synthesized, shown to inhibit Rhizopus chinensis pepsin, and found by Xray crystallography to bind to the enzyme in the GrowMol-predicted mode, Repetitive evaluation of the computer generated templates for synthetic feasibility and optimal enzyme interactions led to the designed compounds.

  DOI：

  10.1021/ol016090+
• 作为产物：
  描述：

  Z-Lys-O-Suc 在 sodium tetrahydroborate 作用下， 生成 (S)-benzyl tert-butyl (6-hydroxyhexane-1,5-diyl)dicarbamate
  参考文献：
  名称：

  Inhibition ofAchromobacterProtease I by Lysinal Derivatives

  摘要：

  化学合成了 Z-Val-、Z-Pro-、Z-Leu-Leu-、Z-Leu-Pro-赖氨醛和 BZ-DL 赖氨醛，并将其作为赖氨酸特异性丝氨酸蛋白酶 Achromobacter protease I (API) 的新型抑制剂进行了测试。在测试的赖氨酸醛衍生物中，Z-缬氨酰-赖氨酸醛是最有效的竞争性抑制剂，在与 Tos-Lys-OMe 进行的酯解试验中，其 Ki 值估计为 6.5 nM。在酰胺分解试验中，Z-Leu-Leu-lysinal 是最有效的抑制剂，其明显的抑制模式是非竞争性的。其他赖氨醛衍生物在酯解和酰胺解试验中的 Kis 值都比 Leupeptin 低 103 倍以上。缺少醛基的 Z-缬氨酰赖氨酸醇是一种竞争性很差的抑制剂。这些结果表明，酰基、酰基氨基酰基和酰基肽基赖氨醇是 Achromobacter 蛋白酶 I 的过渡态抑制剂。

  DOI：

  10.1271/bbb.56.1604

文献信息

• Hydrodehalogenation of Alkyl Iodides with Base-Mediated Hydrogenation and Catalytic Transfer Hydrogenation: Application to the Asymmetric Synthesis of N-Protected α-Methylamines
  作者：Pijus K. Mandal、J. Sanderson Birtwistle、John S. McMurray

  DOI：10.1021/jo500911v

  日期：2014.9.5

  We report a very mild synthesis of N-protected α-methylamines from the corresponding amino acids. Carboxyl groups of amino acids are reduced to iodomethyl groups via hydroxymethyl intermediates. Reductive deiodination to methyl groups is achieved by hydrogenation or catalytic transfer hydrogenation under alkaline conditions. Basic hydrodehalogenation is selective for the iodomethyl group over hydrogenolysis-labile

  我们报告了从相应的氨基酸非常温和地合成 N-保护的 α-甲胺。氨基酸的羧基通过羟甲基中间体被还原为碘甲基。在碱性条件下通过氢化或催化转移氢化实现甲基的还原脱碘。碱性加氢脱卤对碘甲基的选择性高于氢解不稳定的保护基团，例如苄氧羰基、苄酯、苄醚和 9-芴氧基甲基，因此几乎可以将任何受保护的氨基酸转化为相应的 N-保护的 α-甲胺。
• Amphiphilic dendronized homopolymers
  作者：Wen Li、AFang Zhang

  DOI：10.1007/s11426-010-4136-3

  日期：2010.12

  A series of second generation of amphiphilic dendronized homopolymers are efficiently synthesized, and their thermoresponsiveness in aqueous solutions and secondary structures in methanol solutions are described. These polymers are constructed in each repeat unit with various generations of hydrophobic 4-aminoproline and hydrophilic oligoethylene glycol (OEG)-based dendrons, and their over-all hydrophilicity is tuned by varying these dendron generations. Polymers with or without the first generation of proline dendron show good water solubility at room temperature, but exhibit typical thermoresponsive behaviors at elevated temperatures as characterized by turbidity measurements using UV-vis spectroscopy, while the polymer with the secondary generation of proline dendron is not soluble in water. All polymers show ordered secondary structures as evidenced by the optical rotation and circular dichroism experiments. Finally, assembly of these amphiphilic homopolymers into porous films via breath figure (BF) technique is described, and polymer structures are found to show significant influence on the morphology of porous film.

  一系列第二代两亲性树枝化均聚物的合成效率很高，并且描述了它们在水溶液中的热响应性和甲醇溶液中的二级结构。这些聚合物在每个重复单元中构建了不同代数的疏水性4-氨基脯氨酸和亲水性聚氧乙烯甘油（OEG）基树枝状物，并通过改变这些树枝状物的代数来调节它们的整体亲水性。含有或不含第一代脯氨酸树枝状物的聚合物在室温下表现出良好的水溶性，但在升温时表现出典型的热响应行为，这是通过紫外-可见光谱法测定浊度来表征的，而含有第二代脯氨酸树枝状物的聚合物在水中不溶。所有聚合物都显示出有序的二级结构，光学旋转和圆二色实验证明了这一点。最后，描述了这些两亲性均聚物通过呼吸图案（BF）技术组装成多孔膜，并且发现聚合物结构对多孔膜的形态有显著影响。
• Compounds and Compositions as Channel Activating Protease Inhibitors
  申请人：Tully C. David

  公开号：US20070276002A1

  公开（公告）日：2007-11-29

  The invention provides compounds and pharmaceutical compositions thereof, which are useful for modulating channel activating proteases, and methods for using such compounds to treat, ameliorate or prevent a condition associated with a channel activating protease, including but not limited to prostasin, PRSS22, TMPRSS11 (e.g., TMPRSS11B, TMPRSS11E), TMPRSS2, TMPRSS3, TMPRSS4 (MTSP-2), matriptase (MTSP-1), CAP2, CAP3, trypsin, cathepsin A, or neutrophil elastase.

  该发明提供了化合物及其药物组合物，这些化合物用于调节通道激活蛋白酶，以及使用这些化合物来治疗、改善或预防与通道激活蛋白酶相关的疾病的方法，包括但不限于前列腺素、PRSS22、TMPRSS11（例如，TMPRSS11B，TMPRSS11E）、TMPRSS2、TMPRSS3、TMPRSS4（MTSP-2）、膜联蛋白（MTSP-1）、CAP2、CAP3、胰蛋白酶、组织蛋白酶A或中性粒细胞弹性蛋白酶。
• Synthesis of Aminomethylene-<i>gem</i>-bisphosphonates Containing an Aziridine Motif: Studies of the Reaction Scope and Insight into the Mechanism
  作者：Thomas Cheviet、Suzanne Peyrottes

  DOI：10.1021/acs.joc.0c02434

  日期：2021.2.19

  Study of the reaction’s scope and additional experiments indicates that the transformation proceeds via a new mechanism involving the chelation of lithium ion. This last step is crucial for the reaction to occur and disfavors the aziridine ring-opening. A phosphonate–phosphate rearrangement from a α-hydroxybisphosphonate aziridine intermediate is also proposed for the first time. This reaction provides

  获得了广泛的N-氨基甲酰基氮丙啶，然后用二乙基膦酸根阴离子处理，得到α-亚甲基-宝石-双膦酸酯氮丙啶。对反应范围和其他实验的研究表明，转化是通过涉及锂离子螯合的新机理进行的。这最后一步对于反应的发生至关重要，不利于氮丙啶开环。还首次提出了由α-羟基双膦酸酯氮丙啶中间体进行的膦酸酯-磷酸重排。该反应提供了用于合成高度官能化的膦酰化氮丙啶基序的简单方便的方法。
• INHIBITORS OF LYSINE GINGIPAIN
  申请人：Cortexyme, Inc.

  公开号：US20160096830A1

  公开（公告）日：2016-04-07

  The present invention relates generally to therapeutics targeting the bacterium Porphyromonas gingivalis , including its protease Lysine gingipain (Kgp), and their use for the treatment of disorders associated with P. gingivalis infection, including brain disorders such as Alzheimer's disease. In certain embodiments, the invention provides compounds according to Formula I, as described herein, and pharmaceutically acceptable salts thereof.

  本发明通常涉及针对细菌牙龈脓红素Porphyromonas gingivalis及其蛋白酶赖氨酸龈蛋白酶（Kgp）的治疗方法，以及它们用于治疗与P. gingivalis感染相关的疾病，包括脑部疾病如阿尔茨海默病。在某些实施例中，本发明提供根据本文所述的I式化合物及其药用可接受的盐。