6,14-endo-ethano-7α-<1(R)-aminoethyl>tetrahydrothebaine | 127131-01-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 6,14-endo-ethano-7α-<1(R)-aminoethyl>tetrahydrothebaine
• 英文别名: 6,14-endo-ethano-7α-(1(R)-aminoethyl)tetrahydrothebaine
• CAS: 127131-01-5
• 化学式: C₂₃H₃₂N₂O₃
• 分子量: 384.519
• InChiKey: MZUMDSSFSDXNDA-JVHZTCESSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.49
• 重原子数：
  28.0
• 可旋转键数：
  3.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  56.95
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  6,14-endo-etheno-7α-<1(R)-aminoethyl>tetrahydrothebaine 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 26.0h， 以100%的产率得到6,14-endo-ethano-7α-<1(R)-aminoethyl>tetrahydrothebaine
  参考文献：
  名称：

  Electrophilic .alpha.-methylene-.gamma.-lactone and isothiocyanate opioid ligands related to etorphine

  摘要：

  Isothiocyanate and alpha-methylene-gamma-lactone analogues of 6,14-endo-ethenotetrahydrothebaine and -oripavine were prepared with the electrophilic groups being located at C-19 in the C-7 alpha-side chain. Isothiocyanates were prepared in the N-Me and N-CPM (N-cyclopropylmethyl) series, both as the phenols and 3-O-methyl ethers from the diastereomeric amines formed from reductive amination of thevinone (2) and N-(cyclopropylmethyl)northevinone (13). Although addition of the organozinc reagent from methyl alpha-bromomethacrylate to 25 failed, addition to 3-O-protected aldehydes 27 and 35 produced, after subsequent deprotection, alpha-methylene-gamma-lactones 29 and 37, respectively. In the opioid receptor displacement assays against [3H]bremazocine as the radiolabeled ligand, the phenolic compounds were most potent with N-CPM isothiocyanates 20 and 21 showing IC50s of 0.32 and 0.76 nM, respectively, and N-CPM alpha-methylene-gamma-lactone 37 having an IC50 = 1.0 nM. Compound 37 showed irreversible effects in the binding assay which were mu-selective, as demonstrated by analogous experiments using [3H]DAGO, and naloxone was found to protect against the irreversible effects. This observation suggests that a receptor-bound nucleophile is located at a position where it can readily reach the alpha-methylene group of lactone 37.

  DOI：

  10.1021/jm00170a038