2-((1S,2S)-2-aminocyclohexyl)acetic acid

• 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: 2-((1S,2S)-2-aminocyclohexyl)acetic acid
• 英文别名: 2-[(1S,2S)-2-Aminocyclohexyl]acetic acid
• 化学式: C₈H₁₅NO₂
• mdl: MFCD31734131
• 分子量: 157.213
• InChiKey: JZCXXLRGQVHYQJ-BQBZGAKWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.875
• 拓扑面积：
  63.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  二碳酸二叔丁酯 、 2-((1S,2S)-2-aminocyclohexyl)acetic acid 在 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 5.0h， 以96%的产率得到(rac)-cis-2-<<(1,1-dimethylethoxy)carbonyl>amino>cyclohexaneacetic acid
  参考文献：
  名称：

  Analogs of Ac-CCK-7 incorporating dipeptide mimics in place of Met28-Gly29

  摘要：

  A series of analogs of Ac-CCK-7 [Ac-Tyr(SO3H)-Met28-Gly29-Trp-Met-Asp-Phe-NH2, (1)] Were prepared in which the Met28-Gly29 dipeptide was replaced by omega-aminoalkanoic acids. Compounds were assessed in binding assays using homogenated rat pancreatic membranes and bovine striatum as the source of CCK-A and CCK-B receptors, respectively, and for anorectic activity after intraperitoneal administration to rats. The analog incorporating 4-aminobutanoic acid (5) was only 8 times less potent than 1 in the pancreatic binding assay, was more potent in the striatal binding assay, and was more potent than 1 in reducing food intake in rats. Using a bioactive cyclic analog of Ac-CCK-7 as a template, several rigid spacers were designed and tested as substitutes for the Met28-Gly29 dipeptide. The analogs incorporating 3-aminobenzoic acid (20) and (1S)-trans-2-aminocyclopentanecarboxylic acid (26) proved highly effective in the binding assays and as anorectic agents. We hypothesize that for stimulation of CCK-A receptors, the main function of the N-terminal tripeptide of Ac-CCK-7 is to orient the tyrosine sulfate with respect to Trp30 and that the bioactive arrangement of these elements lies among those which are readily available to both 20 and 26. NOESY and distance-constrained molecular dynamics experiments carried out on 20 and 26 identified conformations in which the relative orientation of the tyrosine hydroxide and the alpha-carbon atom of tryptophan were similar, providing the basis for further drug design efforts.

  DOI：

  10.1021/jm00099a005
• 作为产物：
  描述：

  2-((1S,2S)-2-aminocyclohexyl)acetamide 在 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 8.0h， 以82%的产率得到2-((1S,2S)-2-aminocyclohexyl)acetic acid
  参考文献：
  名称：

  Highly Enantioselective γ-Amination of α,β-Unsaturated Acyl Chlorides with Azodicarboxylates: Efficient Synthesis of Chiral γ-Amino Acid Derivatives

  摘要：

  The cinchona alkaloid-catalyzed gamma-amination of alpha,beta-unsaturated acyl chlorides with azodicarboxylates to give the corresponding dihydropyridazinones in good yields with high enantioselectivities has been developed. Reductive ring opening of the dihydropyridazinones afforded series of cyclic and acyclic gamma-amino acid derivatives in good yields with high enantiopurity.

  DOI：

  10.1021/ja206819y

文献信息

• Synthesis of γ-aminobutyric acid analogues of restricted conformation. Part 1. The 2-aminocycloalkylacetic acids
  作者：Peter D. Kennewell、Saroop S. Matharu、John B. Taylor、Robert Westwood、Peter G. Sammes

  DOI：10.1039/p19820002553

  日期：——

  The syntheses of cis- and trans-2-aminocyclopropyl, -cyclobutyl, -cyclopentyl, and -cyclohexylacetic acids as γ-aminobutyric acid analogues of restricted conformation are described. Mass spectral evidence fully supports the stereochemical assignments of the configurational isomers.

  描述了作为受限构象的γ-氨基丁酸类似物的顺式和反式-2-氨基环丙基，-环丁基，-环戊基和-环己基乙酸的合成。质谱证据完全支持构型异构体的立体化学分配。
• Asymmetrische reduktive Aminierung von Cycloalkanonen, 9. Mitt.: Die asymmetrische Synthese GABA-verwandter cycloaliphatischer Aminosäuren
  作者：Farghaly Omar、August W. Frahm

  DOI：10.1002/ardp.19893220803

  日期：——

  wird die asymmetrische Synthese von optisch aktiven cis‐1‐ Aminocyclopentan‐ bzw. cyclohexan‐2‐essig‐ und ‐2‐propionsäure‐Hydrochloriden 5 beschrieben. In einem vierstufigen Verfahren werden die racem. 1‐Cycloalkanon‐2‐essigsäure‐ und 2‐propionsäure‐Derivate 1 mit den chiralen Hilfsaminen R‐(+)‐ und S‐(‐)‐1‐Phenylethylamin zuerst in die Imin‐Isomerengemische 2 überführt, die nach Hydrierung über Raney‐Nickel

  Es wird die asymmetrische Synthese von optisch aktiven cis-1- Aminocyclopentan-bzw。环己-2-essig-和-2-propionsäure-Hydrochloriden 5 beschrieben。在 einem vierstufigen Verfahren werden die racem。1-Cycloalkanon-2-essigsäure- und 2-propionsäure-Derivate 1 mit den chiralen Hilfsaminen R-(+)- und S-(-)-1-Phenylethylamin zuerst in die Imin-Isomerengemische 2 überführt, ung die n Nickel die cis-konfigurierten sekundären
• Analogs of Ac-CCK-7 incorporating dipeptide mimics in place of Met28-Gly29
  作者：Jefferson W. Tilley、Waleed Danho、Shian Jan Shiuey、Irina Kulesha、Joseph Swistok、Raymond Makofske、Joseph Michalewsky、Joseph Triscari、David Nelson

  DOI：10.1021/jm00099a005

  日期：1992.10

  A series of analogs of Ac-CCK-7 [Ac-Tyr(SO3H)-Met28-Gly29-Trp-Met-Asp-Phe-NH2, (1)] Were prepared in which the Met28-Gly29 dipeptide was replaced by omega-aminoalkanoic acids. Compounds were assessed in binding assays using homogenated rat pancreatic membranes and bovine striatum as the source of CCK-A and CCK-B receptors, respectively, and for anorectic activity after intraperitoneal administration to rats. The analog incorporating 4-aminobutanoic acid (5) was only 8 times less potent than 1 in the pancreatic binding assay, was more potent in the striatal binding assay, and was more potent than 1 in reducing food intake in rats. Using a bioactive cyclic analog of Ac-CCK-7 as a template, several rigid spacers were designed and tested as substitutes for the Met28-Gly29 dipeptide. The analogs incorporating 3-aminobenzoic acid (20) and (1S)-trans-2-aminocyclopentanecarboxylic acid (26) proved highly effective in the binding assays and as anorectic agents. We hypothesize that for stimulation of CCK-A receptors, the main function of the N-terminal tripeptide of Ac-CCK-7 is to orient the tyrosine sulfate with respect to Trp30 and that the bioactive arrangement of these elements lies among those which are readily available to both 20 and 26. NOESY and distance-constrained molecular dynamics experiments carried out on 20 and 26 identified conformations in which the relative orientation of the tyrosine hydroxide and the alpha-carbon atom of tryptophan were similar, providing the basis for further drug design efforts.
• Highly Enantioselective γ-Amination of α,β-Unsaturated Acyl Chlorides with Azodicarboxylates: Efficient Synthesis of Chiral γ-Amino Acid Derivatives
  作者：Li-Tao Shen、Li-Hui Sun、Song Ye

  DOI：10.1021/ja206819y

  日期：2011.10.12

  The cinchona alkaloid-catalyzed gamma-amination of alpha,beta-unsaturated acyl chlorides with azodicarboxylates to give the corresponding dihydropyridazinones in good yields with high enantioselectivities has been developed. Reductive ring opening of the dihydropyridazinones afforded series of cyclic and acyclic gamma-amino acid derivatives in good yields with high enantiopurity.