3-O-(tert-butyldimethylsilyl)oripavine | 127131-15-1

• 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: 3-O-(tert-butyldimethylsilyl)oripavine
• 英文别名: [(4R,7aR,12bS)-7-methoxy-3-methyl-2,4,7a,13-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-9-yl]oxy-tert-butyl-dimethylsilane
• CAS: 127131-15-1
• 化学式: C₂₄H₃₃NO₃Si
• 分子量: 411.616
• InChiKey: DYFLUSXIBLYYMH-UWSIMGETSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  29.0
• 可旋转键数：
  3.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  30.93
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  3-O-(tert-butyldimethylsilyl)oripavine 在 锌 作用下， 以 四氢呋喃 、 苯 为溶剂， 反应 12.0h， 生成 3-O-(tert-butyldimethylsilyl)-6,14-endo-etheno-7α-(3-carboxy-3-n-butenyl)tetrahydrooripavine γ-lactone
  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
• 作为产物：
  描述：

  Morphinan-3-ol,7,8-didehydro-4,5-epoxy-6-methoxy-17-methyl-, (5a,6a)- 在 manganese(IV) oxide 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 65.0h， 生成 3-O-(tert-butyldimethylsilyl)oripavine
  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

• KLEIN, PETER;NELSON, WENDEL L.;YAO, YI-HE;SIMON, ERIC J., J. MED. CHEM., 33,(1990) N, C. 2286-2296
  作者：KLEIN, PETER、NELSON, WENDEL L.、YAO, YI-HE、SIMON, ERIC J.

  DOI：——

  日期：——