(1R,2R)-2-(nitromethyl)cyclohexane-1-carbaldehyde | 1292320-78-5

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: (1R,2R)-2-(nitromethyl)cyclohexane-1-carbaldehyde
• 英文别名: (1R,2R)-2-(nitromethyl)cyclohexanecarbaldehyde
• CAS: 1292320-78-5
• 化学式: C₈H₁₃NO₃
• 分子量: 171.196
• InChiKey: GFAAEFMTLJRSAH-YUMQZZPRSA-N

物化性质

• 沸点：
  291.4±13.0 °C(Predicted)
• 密度：
  1.165±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  62.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (1S,2R)-2-(nitromethyl)cyclohexanecarbaldehyde 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 生成 (1R,2R)-2-(nitromethyl)cyclohexane-1-carbaldehyde
  参考文献：
  名称：

  新的预组织 γ-氨基酸作为折叠体构建块

  摘要：

  描述了两种新的非对映体 γ-氨基酸的不对称合成。两个分子都包含一个环己基环以限制 C α -C β键的构象灵活性；它们的不同之处在于环上的顺式与反式立体化学。来自顺式γ 异构体的残基显示支持 α/γ-肽寡聚体中的螺旋二级结构。

  DOI：

  10.1021/ol3008815

文献信息

• Synthetic Studies on CP-225,917 and CP-263,114: Access to Advanced Tetracyclic Systems by Intramolecular Conjugate Displacement and [2,3]-Wittig Rearrangement
  作者：Farzad Malihi、Derrick L. J. Clive、Che-Chien Chang、Minaruzzaman

  DOI：10.1021/jo302467w

  日期：2013.2.1

  An advanced intermediate related to the structures of CP-225,917 and CP-263,114 was constructed by a sequence based on the use of Grob-like fragmentation, intramolecular conjugate displacement, and [2,3]-Wittig rearrangement. A variant of the [2,3]-Wittig rearrangement was developed.

  通过使用Grob样片段化，分子内共轭置换和[2,3] -Wittig重排的序列，构建了与CP-225,917和CP-263,114的结构相关的高级中间体。开发了[2,3] -Wittig重排的变体。
• A γ-Amino Acid That Favors 12/10-Helical Secondary Structure in α/γ-Peptides
  作者：Michael W. Giuliano、Stacy J. Maynard、Aaron M. Almeida、Li Guo、Ilia A. Guzei、Lara C. Spencer、Samuel H. Gellman

  DOI：10.1021/ja5076585

  日期：2014.10.22

  six-membered ring across its Cα-Cβ bond. These studies were made possible by the development of a stereoselective synthesis of N-protected APCH. APCH strongly enforces the α/γ-peptide 12/10-helical secondary structure, which features alternating H-bond directionality. Thus, APCH residues appear to have a conformational propensity distinct from those of other cyclically constrained γ-amino acid residues.

  常规肽中的 H 键合螺旋（仅包含同手性 α-氨基酸残基）具有一致的 H 键合方向性，N 端侧 C=O 到 C 端侧 NH。相比之下，异手性 α-肽可以形成螺旋，其中 H 键的方向性沿着主链交替，因为相邻的酰胺基团取向相反。在由非天然肽骨架形成的螺旋中也可以看到交替的 H 键方向，例如，那些含有 β- 或 γ-氨基酸残基的。在本研究中，我们使用 NMR 光谱和晶体学来评估新型 γ-氨基酸 (1R,2R,3S)-2-(1-氨基丙基)-环己烷甲酸 (APCH) 的构象偏好，其受横跨其 Cα-Cβ 键的六元环。这些研究是通过开发 N 保护的 APCH 的立体选择性合成而成为可能的。APCH 强烈执行 α/γ-肽 12/10-螺旋二级结构，具有交替的 H 键方向性。因此，APCH 残基似乎具有与其他循环受限的 γ-氨基酸残基不同的构象倾向。
• [EN] GAMMA AMINO ACID BUILDING BLOCKS<br/>[FR] ÉLÉMENTS CONSTITUTIFS DE GAMMA-AMINOACIDES
  申请人：WISCONSIN ALUMNI RES FOUND

  公开号：WO2011047190A1

  公开（公告）日：2011-04-21

  The invention provides compounds and methods, for example, to carry out organocatalytic Michael additions of aldehydes to cyclically constrained nitroethylene compounds catalyzed by a pro line derivative to provide cyclically constrained α-substituted-γ-nitro-aldehydes. The reaction can be rendered enantioselective when a chiral pyrrolidine catalyst is used, allowing for Michael adducts in nearly optically pure form (e.g., 96 to >99% e.e.). The Michael adducts can bear a single substituent or dual substituents adjacent to the carbonyl. The Michael adducts can be efficiently converted to cyclically constrained protected γ- amino acid residues, which are essential for systematic conformational studies of γ-peptide foldamers. New methods are also provided to prepare other γ-amino acids and peptides. These new building blocks can be used to prepare foldamers, such as α/γ-peptide foldamers, that adopt specific helical conformations in solution and in the solid state.

  该发明提供了化合物和方法，例如，用于催化贝氏碱衍生物对环状约束硝基乙烯化合物进行醛的有机催化Michael加成，从而提供环状约束的α-取代-γ-硝基醛。当使用手性吡咯烷催化剂时，反应可以实现对映选择性，从而以几乎光学纯形式（例如，96%至>99% e.e.）获得Michael加合物。Michael加合物可以在羰基相邻处携带单取代基或双取代基。Michael加合物可以高效转化为环状约束的保护γ-氨基酸残基，这对于γ-肽折叠体系的系统构象研究至关重要。还提供了制备其他γ-氨基酸和肽的新方法。这些新的构建模块可用于制备折叠体，例如α/γ-肽折叠体，在溶液中和固态中采用特定螺旋构象。
• [EN] PROCESS FOR PREPARING LURASIDONE AND INTERMEDIATE THEREOF<br/>[FR] PROCÉDÉ DE PRÉPARATION DE LURASIDONE ET DE SON INTERMÉDIAIRE
  申请人：ZENTIVA KS

  公开号：WO2015081920A1

  公开（公告）日：2015-06-11

  A new method of synthesis of lurasidone, the substance of the chemical name (3aR,4S,7R,7aS)-2-(((1R,2R)-2-((4-(benzo [d]isothiazol-3-yl)piperazin-1 -yl)methyl)cyclohexyl)methyl)-hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione of structure 1 and its salts. Specifically, a diastereoselective method of preparation of lurasidone based on use of the new intermediate of formula (1)2. The reduction of the nitro group of the intermediate of formula (12) provides the amino intermediate of formula (13), which reacts in the next step with the anhydride of formula (14) with formation of lurasidone of formula (1), which can be further converted to any salt of lurasidone.

  一种合成氯拉西酮的新方法，该物质的化学名称为(3aR,4S,7R,7aS)-2-(((1R,2R)-2-((4-(苯并[d]异噻唑-3-基)哌嗪-1-基)甲基)环己基)甲基)-六氢-1H-4,7-甲基异喹啉-1,3(2H)-二酮结构1及其盐。具体地，一种选择性立体异构合成氯拉西酮的方法，基于使用公式(1)2的新中间体。公式(12)的中间体的硝基团还原得到公式(13)的氨基中间体，该中间体在下一步与公式(14)的酐反应生成公式(1)的氯拉西酮，进而可进一步转化为氯拉西酮的任何盐。
• GAMMA AMINO ACID BUILDING BLOCKS
  申请人：Gellman Samuel Helmer

  公开号：US20110118440A1

  公开（公告）日：2011-05-19

  The invention provides compounds and methods, for example, to carry out organocatalytic Michael additions of aldehydes to cyclically constrained nitroethylene compounds catalyzed by a proline derivative to provide cyclically constrained α-substituted-γ-nitro-aldehydes. The reaction can be rendered enantioselective when a chiral pyrrolidine catalyst is used, allowing for Michael adducts in nearly optically pure form (e.g., 96 to >99% e.e.). The Michael adducts can bear a single substituent or dual substituents adjacent to the carbonyl. The Michael adducts can be efficiently converted to cyclically constrained protected γ-amino acid residues, which are essential for systematic conformational studies of γ-peptide foldamers. New methods are also provided to prepare other γ-amino acids and peptides. These new building blocks can be used to prepare foldamers, such as α/γ-peptide foldamers, that adopt specific helical conformations in solution and in the solid state.