6,14-endo-etheno-7α-<1(R)-isothiocyanatoethyl>tetrahydrooripavine | 127154-02-3

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: 6,14-endo-etheno-7α-<1(R)-isothiocyanatoethyl>tetrahydrooripavine
• 英文别名: 6,14-endo-etheno-7α-(1(R)-isothiocyanatoethyl)tetrahydrooripavine；(1R,2S,6R,14R,15R,19S)-19-[(1R)-1-isothiocyanatoethyl]-15-methoxy-5-methyl-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11,16-tetraen-11-ol
• CAS: 127154-02-3
• 化学式: C₂₃H₂₆N₂O₃S
• 分子量: 410.537
• InChiKey: WTVMVUJOBOGEOT-JVHZTCESSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  86.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-[(5alpha,7alpha)-4,5-环氧-3,6-二甲氧基-17-甲基-6,14-乙烯桥吗喃-7-基]乙酮 在 乙酸铵 、 氢氧化钾 、 sodium cyanoborohydride 、 碳酸氢钠 作用下， 以 甲醇 、 二氯甲烷 、 二乙二醇 为溶剂， 反应 75.66h， 生成 6,14-endo-etheno-7α-<1(R)-isothiocyanatoethyl>tetrahydrooripavine
  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

文献信息

• Electrophilic .alpha.-methylene-.gamma.-lactone and isothiocyanate opioid ligands related to etorphine
  作者：Peter Klein、Wendel L. Nelson、Yi He Yao、Eric J. Simon

  DOI：10.1021/jm00170a038

  日期：1990.8

  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.