methyl 2-benzyloxycarbonylamino-(1R,2S)-cyclobutane-1-carboxylate | 221158-91-4

• 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: methyl 2-benzyloxycarbonylamino-(1R,2S)-cyclobutane-1-carboxylate
• 英文别名: methyl (1R,2S)-2-benzyloxycarbonylaminocyclobutane-1-carboxylate；methyl (1R,2S)-2-(benzyloxycarbonylamino)cyclobutanecarboxylate；methyl rel-(1R,2S)-2-{[(benzyloxy)carbonyl]amino}cyclobutanecarboxylate；methyl (1R,2S)-2-(phenylmethoxycarbonylamino)cyclobutane-1-carboxylate
• CAS: 221158-91-4
• 化学式: C₁₄H₁₇NO₄
• 分子量: 263.293
• InChiKey: UOISHCCHGFCALE-NEPJUHHUSA-N

物化性质

• 沸点：
  401.9±44.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 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：

  methyl 2-benzyloxycarbonylamino-(1R,2S)-cyclobutane-1-carboxylate 在 palladium on activated charcoal 氢气 、 potassium carbonate 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、202.65 kPa 条件下， 反应 6.0h， 生成 (+/-)-cis-2-amino-1-cyclobutanecarboxylic acid
  参考文献：
  名称：

  Enantioselective synthetic approaches to cyclopropane and cyclobutane β-amino acids: synthesis and structural study of a conformationally constrained β-dipeptide

  摘要：

  Synthetic approaches to carbocyclic compounds, namely cyclopropane and cyclobutane beta -amino acids, are presented. One of them is based on enzymatic desymmetrization of meso diesters, leading to the enantioselective production of cis-hemiesters, which afforded beta -amino acids through Curtius rearrangements. The enantiomeric excess for the cyclobutane derivatives was 91% whereas the cyclopropanes were obtained in 63% ee. According to another strategy, an enantiomerically pure cyclopropane trans-beta -amino acid, bearing a quaternary center, has been synthesized from a homochiral precursor easily available from D-glyceraldehyde. The preparation and structural investigation of the first synthesized cyclobutane containing dipeptide is also described. A hairpin-like conformation of this molecule in the solid state has been demonstrated by X-ray structural analysis, showing crystal packing induced by the presence of the rigid cyclobutane moiety and the formation of intermolecular hydrogen bonds. NMR experiments confirmed that these molecules also tend to produce aggregates in solution. On the contrary, theoretical calculations suggest that intramolecular interactions are important in the gas phase, as expected. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(00)00297-4
• 作为产物：
  描述：

  methyl hydrogen (-)-(1R,2S)-cyclobutane-1,2-dicarboxylate 在 氯甲酸乙酯 、 三乙胺 作用下， 以 丙酮 为溶剂， 反应 6.5h， 生成 methyl 2-benzyloxycarbonylamino-(1R,2S)-cyclobutane-1-carboxylate
  参考文献：
  名称：

  Enantioselective synthetic approaches to cyclopropane and cyclobutane β-amino acids: synthesis and structural study of a conformationally constrained β-dipeptide

  摘要：

  Synthetic approaches to carbocyclic compounds, namely cyclopropane and cyclobutane beta -amino acids, are presented. One of them is based on enzymatic desymmetrization of meso diesters, leading to the enantioselective production of cis-hemiesters, which afforded beta -amino acids through Curtius rearrangements. The enantiomeric excess for the cyclobutane derivatives was 91% whereas the cyclopropanes were obtained in 63% ee. According to another strategy, an enantiomerically pure cyclopropane trans-beta -amino acid, bearing a quaternary center, has been synthesized from a homochiral precursor easily available from D-glyceraldehyde. The preparation and structural investigation of the first synthesized cyclobutane containing dipeptide is also described. A hairpin-like conformation of this molecule in the solid state has been demonstrated by X-ray structural analysis, showing crystal packing induced by the presence of the rigid cyclobutane moiety and the formation of intermolecular hydrogen bonds. NMR experiments confirmed that these molecules also tend to produce aggregates in solution. On the contrary, theoretical calculations suggest that intramolecular interactions are important in the gas phase, as expected. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(00)00297-4

文献信息

• [EN] TRIAZACYCLODODECANSULFONAMIDE ("TCD")-BASED PROTEIN SECRETION INHIBITORS<br/>[FR] INHIBITEURS DE SÉCRÉTION DE PROTÉINE À BASE DE TRIAZACYCLODODÉCANSULFONAMIDE ("TCD")
  申请人：KEZAR LIFE SCIENCES

  公开号：WO2019178510A1

  公开（公告）日：2019-09-19

  Provided herein are triazacyclododecansulfonamide ("TCD")-based protein secretion inhibitors, such as inhibitors of Sec61, methods for their preparation, related pharmaceutical compositions, and methods for using the same. For example, provided herein are compounds of Formula (I) and pharmaceutically acceptable salts and compositions including the same. The compounds disclosed herein may be used, for example, in the treatment of diseases including inflammation and/or cancer.

  本文提供了基于三氮杂环十二烷磺酰胺（"TCD"）的蛋白质分泌抑制剂，例如Sec61的抑制剂，其制备方法，相关的药物组合物，以及使用它们的方法。例如，本文提供了符合Formula（I）的化合物及其药用盐和包括它们的组合物。本文披露的化合物可以用于治疗炎症和/或癌症等疾病。
• ORNITHINE DERIVATIVE
  申请人：Astellas Pharma Inc.

  公开号：EP2141147A1

  公开（公告）日：2010-01-06

  Provided is a compound which is useful as a therapeutic agent for chronic renal insufficiency and a therapeutic agent for diabetic nephropathy. The present inventors have made extensive studies on an ornithine derivative having an antagonistic action against an EP4 receptor, and as a result, they have found that by introducing cycloalkanediyl at a C terminal of the ornithine part of the compound of the present invention, the physicochemical properties such as solubility, and the like can be improved, thereby giving further preferred properties as a pharmaceutical. Therefore, they have completed the present invention. The compound of the present invention exhibits a good antagonistic action against an EP4 receptor, and thus, it is useful as a therapeutic agent for chronic renal insufficiency and diabetic nephropathy.

  提供了一种化合物，可用作慢性肾功能不全的治疗剂和糖尿病肾病的治疗剂。目前的发明人对具有对EP4受体拮抗作用的鸟氨酸衍生物进行了广泛研究，结果发现通过在目前发明的化合物的鸟氨酸部分的C末端引入环烷基，可以改善物理化学性质，如溶解性等，从而赋予其作为药物的更优越性质。因此，他们完成了这项发明。目前发明的化合物对EP4受体表现出良好的拮抗作用，因此，它可用作慢性肾功能不全和糖尿病肾病的治疗剂。
• Diastereodivergent Synthesis of Chiral<i>vic</i>-Disubstituted-Cyclobutane Scaffolds: 1,3-Amino Alcohol and 1,3-Diamine Derivatives - Preliminary Use in Organocatalysis
  作者：Enric Mayans、Albert Gargallo、Ángel Álvarez-Larena、Ona Illa、Rosa M. Ortuño

  DOI：10.1002/ejoc.201201307

  日期：2013.3

  The synthesis of chiral cyclobutane containing 1,3-amino alcohols and 1,3-diamines has been accomplished in an efficient and diastereodivergent manner from a common chiral precursor. Regioselective manipulation of functional groups in the prepared products provides an easy entry to several derivatives, such as thioureas. Preliminary results on the use of these compounds as bifunctional organocatalysts

  含有 1,3-氨基醇和 1,3-二胺的手性环丁烷的合成是从常见的手性前体以有效和非对映发散的方式完成的。对制备的产品中的官能团进行区域选择性操作，可以轻松获得几种衍生物，例如硫脲。报道了将这些化合物用作双功能有机催化剂的初步结果。
• Ornithine derivative
  申请人：Astellas Pharma Inc.

  公开号：US08030489B2

  公开（公告）日：2011-10-04

  Provided is a compound which is useful as a therapeutic agent for chronic renal insufficiency and a therapeutic agent for diabetic nephropathy. The present inventors have made extensive studies on an ornithine derivative having an antagonistic action against an EP4 receptor, and as a result, they have found that by introducing cycloalkanediyl at a C terminal of the ornithine part of the compound of the present invention, the physicochemical properties such as solubility, and the like can be improved, thereby giving further preferred properties as a pharmaceutical. Therefore, they have completed the present invention. The compound of the present invention exhibits a good antagonistic action against an EP4 receptor, and thus, it is useful as a therapeutic agent for chronic renal insufficiency and diabetic nephropathy.

  提供的是一种化合物，可用作慢性肾功能不全的治疗剂和糖尿病肾病的治疗剂。本发明人对具有对抗EP4受体作用的鸟氨酸衍生物进行了广泛的研究，结果发现通过在化合物的鸟氨酸部分的C末端引入环状烷基，可以改善其物理化学性质，例如溶解度等，从而赋予其更优越的药物特性。因此，他们完成了本发明。本发明的化合物显示出良好的对抗EP4受体的作用，因此可用作慢性肾功能不全和糖尿病肾病的治疗剂。
• Stereoselective synthesis of (−)-(1R,2S)-2-aminocyclobutane-1-carboxylic acid, a conformationally constrained β-amino acid
  作者：Marta Martı́n-Vilà、Cristina Minguillón、Rosa M. Ortuño

  DOI：10.1016/s0957-4166(98)00462-5

  日期：1998.12

  The title compound as well as some derivatives have been synthesized for the first time in optically active form by means of a chemoenzymatic transformation used to induce asymmetry in achiral precursors. The enantio- and diastereomeric purity has been determined by HPLC and NMR techniques. (C) 1998 Elsevier Science Ltd. All rights reserved.