methyl (S)-2-((tert-butoxycarbonyl)amino)-3-(2,6-dimethylphenyl)propanoate

• 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: methyl (S)-2-((tert-butoxycarbonyl)amino)-3-(2,6-dimethylphenyl)propanoate
• 英文别名: methyl (2S)-3-(2,6-dimethylphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate
• 化学式: C₁₇H₂₅NO₄
• 分子量: 307.39
• InChiKey: QJULGQCZCWGELD-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 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 (S)-2-((tert-butoxycarbonyl)amino)-3-(2,6-dimethylphenyl)propanoate 在 lithium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.0h， 以100%的产率得到(S)-2-((tert-butoxycarbonyl)amino)-3-(2,6-dimethylphenyl)propanoic acid
  参考文献：
  名称：

  Rapid Synthesis of Boc-2′,6′-dimethyl-l-tyrosine and Derivatives and Incorporation into Opioid Peptidomimetics

  摘要：

  The unnatural amino acid 2',6'-dimethyl-L-tyrosine has found widespread use in the development of synthetic opioid ligands. Opioids featuring this residue at the N-terminus often display superior potency at one or more of the opioid receptor types, but the availability of the compound is hampered by its cost and difficult synthesis. We report here a short, three-step synthesis of Boc-2',6'-dimethyl-L-tyrosine (3a) utilizing a microwave-assisted Negishi coupling for the key carbon-carbon bond forming step, and employ this chemistry for the expedient synthesis of other unnatural tyrosine derivatives. Three of these derivatives (3c, 3d, 30 have not previously been examined as Tyr(1) replacements in opioid ligands. We describe the incorporation of these tyrosine derivatives in a series of opioid peptidomimetics employing our previously reported tetrahydroquinoline (THQ) scaffold, and the binding and relative efficacy of each of the analogues at the three opioid receptor subtypes: mu (MOR), delta (DOR), and kappa (KOR).

  DOI：

  10.1021/acsmedchemlett.5b00344
• 作为产物：
  描述：

  Boc-L-丝氨酸甲酯 在 2-双环己基膦-2',6'-二甲氧基联苯 、 咪唑 、 tris-(dibenzylideneacetone)dipalladium(0) 、 碘 、 三苯基膦 、 锌 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 methyl (S)-2-((tert-butoxycarbonyl)amino)-3-(2,6-dimethylphenyl)propanoate
  参考文献：
  名称：

  Rapid Synthesis of Boc-2′,6′-dimethyl-l-tyrosine and Derivatives and Incorporation into Opioid Peptidomimetics

  摘要：

  The unnatural amino acid 2',6'-dimethyl-L-tyrosine has found widespread use in the development of synthetic opioid ligands. Opioids featuring this residue at the N-terminus often display superior potency at one or more of the opioid receptor types, but the availability of the compound is hampered by its cost and difficult synthesis. We report here a short, three-step synthesis of Boc-2',6'-dimethyl-L-tyrosine (3a) utilizing a microwave-assisted Negishi coupling for the key carbon-carbon bond forming step, and employ this chemistry for the expedient synthesis of other unnatural tyrosine derivatives. Three of these derivatives (3c, 3d, 30 have not previously been examined as Tyr(1) replacements in opioid ligands. We describe the incorporation of these tyrosine derivatives in a series of opioid peptidomimetics employing our previously reported tetrahydroquinoline (THQ) scaffold, and the binding and relative efficacy of each of the analogues at the three opioid receptor subtypes: mu (MOR), delta (DOR), and kappa (KOR).

  DOI：

  10.1021/acsmedchemlett.5b00344

文献信息

• Heterocyclic derivatives as opioid receptor modulators
  申请人：Janssen Pharmaceutica NV

  公开号：EP2275105A1

  公开（公告）日：2011-01-19

  This invention is directed towards compounds of formula (II) as intermediates for opioid receptor modulators, antagonists, and agonists useful for the treatment of opioid modulated disorders such as pain and gastrointestinal disorders.

  本发明的目的是将式（II）化合物作为阿片受体调节剂、拮抗剂和激动剂的中间体，用于治疗阿片受体调节紊乱，如疼痛和胃肠功能紊乱。
• US7202381B2
  申请人：——

  公开号：US7202381B2

  公开（公告）日：2007-04-10
• US7659402B2
  申请人：——

  公开号：US7659402B2

  公开（公告）日：2010-02-09