tert-butyl (R)-(methoxycarbonyl)(cyclohexyl)methylcarbamate | 188348-02-9

• 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: tert-butyl (R)-(methoxycarbonyl)(cyclohexyl)methylcarbamate
• 英文别名: Boc-D-Chg-Ome；methyl (2R)-2-cyclohexyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]acetate
• CAS: 188348-02-9
• 化学式: C₁₄H₂₅NO₄
• 分子量: 271.357
• InChiKey: ABLGTTUCCPCVGX-LLVKDONJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (R)-(methoxycarbonyl)(cyclohexyl)methylcarbamate 在 二异丁基氢化铝 作用下， 生成 (2R)-2-(1,1-dimethylethoxycarbonylamino)-2-cyclohexylethanal
  参考文献：
  名称：

  二氢喹唑啉衍生的强效β-分泌酶抑制剂的基于结构的设计、合成和生物学评价

  摘要：

  描述了一系列包含噻唑和吡唑衍生 P2-配体的二氢喹唑啉衍生 β-分泌酶抑制剂的基于结构的设计、合成和生物学评价。我们已鉴定出抑制剂4f，其在酶抑制 (K i  = 13 nM) 和细胞 (IC 50  = 21 nM 在神经母细胞瘤细胞中) 测定中表现出强效。基于3a结合 β-分泌酶的 X 射线结构创建了4f模型。该模型建议了活性位点中可能的相互作用。

  DOI：

  10.1016/j.bmcl.2012.07.043
• 作为产物：
  描述：

  Boc-D-苯甘氨酸 在 4-二甲氨基吡啶 、 氢气 、 N,N'-二异丙基碳二亚胺 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 80.0 ℃ 、1.01 MPa 条件下， 反应 51.08h， 生成 tert-butyl (R)-(methoxycarbonyl)(cyclohexyl)methylcarbamate
  参考文献：
  名称：

  聚硅烷固定的 Rh-Pt 双金属纳米粒子作为强大的芳烃加氢催化剂：合成、间歇和流动条件下的反应以及反应机理

  摘要：

  芳烃的氢化不仅是储氢和运输氢的重要反应，也是合成药物和生物活性化合物等功能性分子的重要反应。在这里，我们描述了非均相 Rh-Pt 双金属纳米颗粒催化剂的开发，用于以廉价的聚硅烷作为载体氢化芳烃。该催化剂可用于间歇和连续流动系统，在温和条件下具有高性能，并显示出广泛的底物通用性。在连续流动系统中，只需将底物和 1 个大气压的 H2 通过装有催化剂的柱子即可获得产物。值得注意的是，在流动系统中观察到比在间歇系统中高得多的催化性能，并且在连续流动条件下表现出极强的耐久性（> 连续运行50天；营业额 >3.4 × 105）。此外，研究了反应机理的细节以及批次和流动中不同动力学的起源，并将获得的知识应用于开发含有两个芳环的化合物的完全选择性芳烃氢化以合成活性药物成分。

  DOI：

  10.1021/jacs.8b06015

文献信息

• Design, synthesis, and structure–activity relationship study of conformationally constrained analogs of indole-3-carboxamides as novel CB1 cannabinoid receptor agonists
  作者：Takao Kiyoi、Mark York、Stuart Francis、Darren Edwards、Glenn Walker、Andrea K. Houghton、Jean E. Cottney、James Baker、Julia M. Adam

  DOI：10.1016/j.bmcl.2010.06.067

  日期：2010.8

  Novel tricyclic indole-3-carboxamides were synthesized as structurally restricted analogs of bicyclic indoles, and found to be potent CB1 cannabinoid receptor agonists. The CB1 agonist activity depended on the absolute configuration of the chiral center of the tricyclic ring. The preferred enantiomer was more potent than the structurally unconstrained lead compound. Structure–activity relationships

  新型三环吲哚-3-羧酰胺被合成为双环吲哚的结构受限类似物，并被发现是有效的CB1大麻素受体激动剂。CB1激动剂活性取决于三环手性中心的绝对构型。优选的对映异构体比结构不受限制的铅化合物更有效。还研究了吲哚C-3位置酰胺侧链的结构活性关系。
• A Multikilogram-Scale Synthesis of (R)-Methyl 2-[(1r,4R)-4-(tert-Butoxy­carbonylamino)cyclohexyl]-2-(2-nitrophenylsulfonamido)acetate - A Doubly Protected Building Block with Three Points of Variation
  作者：Gregory Carr、Sam Butterworth、Phil Walker、Folkert Reck、Bolin Geng、Lakshmipathi Pandarinathan

  DOI：10.1055/s-0031-1289724

  日期：2012.3

  A robust and scalable synthesis of (R)-methyl 2-[(1r,4R)-4-(tert-butoxycarbonylamino)cyclohexyl]-2-(2-nitrophenylsulfon­amido)acetate is reported. This serves as a scaffold for the preparation of trans-substituted aminocyclohexanes. The key synthetic step is the reduction of d-4-hydroxyphenylglycine, or a protected equivalent, to achieve the required regiochemistry across the cyclohexyl ring.

  报告了 2-[(1r,4R)-4-(叔丁氧羰基氨基)环己基]-2-(2-硝基苯磺酰胺基)乙酸(R)-甲基酯的可靠且可扩展的合成方法。它是制备反式取代氨基环己烷的支架。关键的合成步骤是还原 d-4- 羟基苯甘氨酸或受保护的等价物，以实现环己基环上所需的区域化学反应。
• Synthesis of novel potent hepatitis C virus NS3 protease inhibitors: Discovery of 4-hydroxy-cyclopent-2-ene-1,2-dicarboxylic acid as a N-acyl-l-hydroxyproline bioisostere
  作者：Fredrik Thorstensson、Fredrik Wångsell、Ingemar Kvarnström、Lotta Vrang、Elizabeth Hamelink、Katarina Jansson、Anders Hallberg、Åsa Rosenquist、Bertil Samuelsson

  DOI：10.1016/j.bmc.2006.10.044

  日期：2007.1

  Potent tetrapeptidic inhibitors of the HCV NS3 protease have been developed incorporating 4-hydroxy-cyclopent-2-ene-1,2-dicarboxylic acid as a new N-acyl-L-hydroxyproline mimic. The hydroxycyclopentene template was synthesized in eight steps from commercially available, (syn)-tetrahydrophthalic anhydride. Three different amino acids were explored in the PI-position and in the P2-position the hydroxyl group of the cyclopentene template was substituted with 7-methoxy-2-phenyl-quinolin-4-ol. The P3/P4-positions were then optimized from a set of six amino acid derivatives. All inhibitors were evaluated in an in vitro assay using the full-length NS3 protease. Several potent inhibitors were identified, the most promising exhibiting a K-i value of 1.1 nM. (c) 2006 Elsevier Ltd. All rights reserved.
• Chiral electrophilic “glycinal” equivalents. New synthons for optically active α-amino acids and 4-substituted 2-oxazolidinones
  作者：Hirofumi Matsunaga、Tadao Ishizuka、Takehisa Kunieda

  DOI：10.1016/s0040-4020(96)01077-0

  日期：1997.1

  The thermal reaction of 3-[(IS)-2-alkoxy-1-apocamphanecarbonyl]-2-oxazolones (21a-c) with dialkyl azodicarboxylates (9) results in exclusive formation of [4 + 2] type cycloadducts (22 and 23) with moderate levels of diastereofacial selection (up to 72% d.e.). The diastereomers thus obtained were readily purified and subsequent treatment with acidic methanol followed by removal of the auxiliary with LiBH4/MeOH (1:2) gave optically pure 4-methoxy-5-hydrazino-2-oxazolidinones (26 and 27), which serve as alpha-aminoaldehyde templates useful for the synthesis of a wide variety of optically active alpha-amino acids as well as 4-alkyl and 4-aryl-2-oxazolidinones. (C) 1997, Elsevier Science Ltd.