(S)-2-amino-N-(naphthalene-1-yl)-3-phenylpropanamide | 112077-80-2

• 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: (S)-2-amino-N-(naphthalene-1-yl)-3-phenylpropanamide
• 英文别名: (2S)-2-amino-N-naphthalen-1-yl-3-phenylpropanamide
• CAS: 112077-80-2
• 化学式: C₁₉H₁₈N₂O
• 分子量: 290.365
• InChiKey: SQDPSDKXONPFBJ-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-2-amino-N-(naphthalene-1-yl)-3-phenylpropanamide 在 N-甲基吗啉 、 盐酸 、 氯甲酸异丁酯 、 亚硝酸异戊酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 ((S)-1-(4-Hydroxy-benzyl)-2-{(S)-2-[(S)-1-(naphthalen-1-ylcarbamoyl)-2-phenyl-ethylcarbamoyl]-pyrrolidin-1-yl}-2-oxo-ethyl)-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Development of Potent Bifunctional Endomorphin-2 Analogues with Mixed μ-/δ-Opioid Agonist and δ-Opioid Antagonist Properties

  摘要：

  The C terminus of endomorphin-2 (EM-2) analogues (Tyr-Pro-Phe-NH-X) was modified with aromatic, heteroaromatic, or aliphatic groups (X = phenethyl,benzyl, phenyl, naphthyl, pyridyl, quinolyl, isoquinolyl, tert-butyl, cyclohexyl, or adamantyl; 3-18) to study their effect on opioid activity. Only 9 (1-naphthyl), 11 (5-quinolyl), 16 (cyclohexyl), and 18 (2-adamantyl) exhibited mu-opioid receptor affinity in the nanomolar range (K-i = 2.41-6.59 nM), which, however, was 3- to 10-fold less than the parent peptide. Replacement of Tyr(1) by Dmt (2',6'-dimethyl-L-tyrosine) (19-32) exerted profound effects: (i) acquisition of high mu-opioid receptor affinity (K-i = 0.11-0.52 nM) except 23 (Ph); (ii) presence of potent functional mu-opioid receptor agonism (IC50 < 1 nM) for 19 ([Dmt(1)]EM-2), 27 (1-naphthyl), 29 (5-quinolyl), and 32 (5-isolquinolyl); (iii) association of weak delta-opioid antagonist activity (pA(2) = 5.41-7.18) except 19 ([Dmt(1)]EM-2), 20 (H), 27 (1-naphthyl), and in particular 29 (5-quinolyl) with its potent delta-agonism (IC50 = 0.62 nM, pA(2) = 5.88); (iv) production of antinociception after ic administration of 32 (5-isoquinolyl) in mice, a bioactivity absent in the corresponding Tyr(1) analogue (14); and (v) preferential cis orientation (cis/trans = 3:2 to 7:3) at the Dmt-Pro amide bond, in contrast to the Tyr-Pro amide trans orientation (cis/trans = 1:2 to 1:3). Thus, [Dmt(1)]EM-2 analogues with hydrophobic C-terminal extensions provide model compounds with potent mu-opioid receptor bioactivity and dual functional agonism.

  DOI：

  10.1021/jm030649p
• 作为产物：
  描述：

  N-苄氧羰基-L-苯丙氨酸 N-羟基琥珀酰亚胺酯 在 氢溴酸 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 生成 (S)-2-amino-N-(naphthalene-1-yl)-3-phenylpropanamide
  参考文献：
  名称：

  Nickel complexes from α-amino amides as efficient catalysts for the enantioselective Et2Zn addition to benzaldehyde

  摘要：

  Ni2+ complexes derived from simple alpha-amino amides catalyze very efficiently the addition of Et2Zn to benzaldehyde, giving (S)-1-phenylethanol as the major isomer in most cases (94% yield, 97% ee for R=Bn). The nature of the substituent on the amide nitrogen atom seems to play a key role in determining the asymmetric induction observed. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(03)01705-2

文献信息

• Amino Amide Organocatalysts for Asymmetric Michael Addition of β-Keto Esters with β-Nitroolefins
  作者：Isiaka Alade Owolabi、Madhu Chennapuram、Chigusa Seki、Yuko Okuyama、Eunsang Kwon、Koji Uwai、Michio Tokiwa、Mitsuhiro Takeshita、Hiroto Nakano

  DOI：10.1246/bcsj.20180302

  日期：2019.3.15

  Asymmetric Michael addition of β-keto esters with trans-β-nitroolefins using chiral amino amide organocatalyst was tried and afforded synthetically useful chiral Michael adducts in both excellent c...

  使用手性氨基酰胺有机催化剂尝试了β-酮酯与反式-β-硝基烯烃的不对称迈克尔加成，并以两种优异的方式提供了合成有用的手性迈克尔加合物。
• Enantioselective nickel-catalyzed conjugate addition of dialkylzinc to chalcones using chiral α-amino amides
  作者：Jorge Escorihuela、M. Isabel Burguete、Santiago V. Luis

  DOI：10.1016/j.tetlet.2008.09.120

  日期：2008.11

  A series of alpha-amino amides derived from natural amino acids (alanine, valine, phenylalanine, isoleucine, and phenylglycine) have been synthesized and fully characterized. Their Ni(II) complexes prepared from Ni(acac)(2) catalyze the enantioselective conjugate addition of diethylzinc to chalcones in high yields and in good enantioselectivities (up to 84%). The side chain of the amino acid and the substituents in the amide nitrogen govern the enantioselectivity of the catalytic process. (c) 2008 Elsevier Ltd. All rights reserved.
• Development of Potent Bifunctional Endomorphin-2 Analogues with Mixed μ-/δ-Opioid Agonist and δ-Opioid Antagonist Properties
  作者：Yoshio Fujita、Yuko Tsuda、Tingyou Li、Takashi Motoyama、Motohiro Takahashi、Yoshiro Shimizu、Toshio Yokoi、Yusuke Sasaki、Akihiro Ambo、Atsuko Kita、Yunden Jinsmaa、Sharon D. Bryant、Lawrence H. Lazarus、Yoshio Okada

  DOI：10.1021/jm030649p

  日期：2004.7.1

  The C terminus of endomorphin-2 (EM-2) analogues (Tyr-Pro-Phe-NH-X) was modified with aromatic, heteroaromatic, or aliphatic groups (X = phenethyl,benzyl, phenyl, naphthyl, pyridyl, quinolyl, isoquinolyl, tert-butyl, cyclohexyl, or adamantyl; 3-18) to study their effect on opioid activity. Only 9 (1-naphthyl), 11 (5-quinolyl), 16 (cyclohexyl), and 18 (2-adamantyl) exhibited mu-opioid receptor affinity in the nanomolar range (K-i = 2.41-6.59 nM), which, however, was 3- to 10-fold less than the parent peptide. Replacement of Tyr(1) by Dmt (2',6'-dimethyl-L-tyrosine) (19-32) exerted profound effects: (i) acquisition of high mu-opioid receptor affinity (K-i = 0.11-0.52 nM) except 23 (Ph); (ii) presence of potent functional mu-opioid receptor agonism (IC50 < 1 nM) for 19 ([Dmt(1)]EM-2), 27 (1-naphthyl), 29 (5-quinolyl), and 32 (5-isolquinolyl); (iii) association of weak delta-opioid antagonist activity (pA(2) = 5.41-7.18) except 19 ([Dmt(1)]EM-2), 20 (H), 27 (1-naphthyl), and in particular 29 (5-quinolyl) with its potent delta-agonism (IC50 = 0.62 nM, pA(2) = 5.88); (iv) production of antinociception after ic administration of 32 (5-isoquinolyl) in mice, a bioactivity absent in the corresponding Tyr(1) analogue (14); and (v) preferential cis orientation (cis/trans = 3:2 to 7:3) at the Dmt-Pro amide bond, in contrast to the Tyr-Pro amide trans orientation (cis/trans = 1:2 to 1:3). Thus, [Dmt(1)]EM-2 analogues with hydrophobic C-terminal extensions provide model compounds with potent mu-opioid receptor bioactivity and dual functional agonism.
• Nickel complexes from α-amino amides as efficient catalysts for the enantioselective Et2Zn addition to benzaldehyde
  作者：M.Isabel Burguete、Manuel Collado、Jorge Escorihuela、Francisco Galindo、Eduardo Garcı́a-Verdugo、Santiago V Luis、Marı́a J Vicent

  DOI：10.1016/s0040-4039(03)01705-2

  日期：2003.9

  Ni2+ complexes derived from simple alpha-amino amides catalyze very efficiently the addition of Et2Zn to benzaldehyde, giving (S)-1-phenylethanol as the major isomer in most cases (94% yield, 97% ee for R=Bn). The nature of the substituent on the amide nitrogen atom seems to play a key role in determining the asymmetric induction observed. (C) 2003 Elsevier Ltd. All rights reserved.