4,5α-epoxy-7β,8β-methano-3-methoxy-17-methylmorphinan-6α-ol | 78518-08-8

• 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: 4,5α-epoxy-7β,8β-methano-3-methoxy-17-methylmorphinan-6α-ol
• CAS: 78518-08-8
• 化学式: C₁₉H₂₃NO₃
• 分子量: 313.397
• InChiKey: NZDWKUUQWLATLC-RBTRTSLOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.58
• 重原子数：
  23.0
• 可旋转键数：
  1.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  41.93
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  4,5α-epoxy-7β,8β-methano-3-methoxy-17-methylmorphinan-6α-ol 在 乙酸酐 、 二甲基亚砜 作用下， 反应 1.0h， 以70%的产率得到7beta,8beta-甲桥二氢可待因酮
  参考文献：
  名称：

  Analgesic narcotic antagonists. 6. 7.beta.,8.beta.-Methano- and 7.beta.,8.beta.-epoxydihydrocodeinone

  摘要：

  Reaction of codeinone (2) with CH2N2 in the presence of Pd(OAc)2 yielded mixtures of starting material and (2) and 7 beta, 8 beta-methanodihydrocodeinone (3). Initial resolution of this mixture was achieved via carbonyl reduction followed by chromatography to give pure 7 beta, 8 beta-methanodihydrocodeine (4), which was oxidized to 3. Reaction of the mixture containing 2 and 3 with mercaptoethanol and NaOH [2 leads to 8 beta-[(hydroxyethyl)thio]dihydrocodeinone (5)] allowed selective crystallization of 3. The beta configuration of the cyclopropane ring in 3 was established by cleavage with aqueous HCl to give the 8 beta-(chloromethyl) compound 6, followed by carbonyl reduction and dehalogenation to 8 beta-methyldihydrocodeine (8). Reaction of the N-(cycloalkylmethyl) derivatives (13 and 18) of 2 with CH2N2/Pd(OA)2 gave potential mixed agonist-antagonists and 14 and 19, which were purified by reduction-oxidation (14) or mercaptoethanol-base treatment (19). Compound 2, on oxidation with alkaline peroxide, gave the previously reported 7 beta, 8 beta-epoxydihydrocodeinone (22) as the hemimethanol ketal (21). Compound 3 was about ninefold more potent an agonist than dihydrocodeine, and the N-(cyclopropylmethyl)-7 beta, 8 beta-methano compound 19 had moderately potent mixed agonist-narcotic antagonist properties.

  DOI：

  10.1021/jm00138a016
• 作为产物：
  描述：

  7beta,8beta-甲桥二氢可待因酮 在 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以75%的产率得到4,5α-epoxy-7β,8β-methano-3-methoxy-17-methylmorphinan-6α-ol
  参考文献：
  名称：

  Analgesic narcotic antagonists. 6. 7.beta.,8.beta.-Methano- and 7.beta.,8.beta.-epoxydihydrocodeinone

  摘要：

  Reaction of codeinone (2) with CH2N2 in the presence of Pd(OAc)2 yielded mixtures of starting material and (2) and 7 beta, 8 beta-methanodihydrocodeinone (3). Initial resolution of this mixture was achieved via carbonyl reduction followed by chromatography to give pure 7 beta, 8 beta-methanodihydrocodeine (4), which was oxidized to 3. Reaction of the mixture containing 2 and 3 with mercaptoethanol and NaOH [2 leads to 8 beta-[(hydroxyethyl)thio]dihydrocodeinone (5)] allowed selective crystallization of 3. The beta configuration of the cyclopropane ring in 3 was established by cleavage with aqueous HCl to give the 8 beta-(chloromethyl) compound 6, followed by carbonyl reduction and dehalogenation to 8 beta-methyldihydrocodeine (8). Reaction of the N-(cycloalkylmethyl) derivatives (13 and 18) of 2 with CH2N2/Pd(OA)2 gave potential mixed agonist-antagonists and 14 and 19, which were purified by reduction-oxidation (14) or mercaptoethanol-base treatment (19). Compound 2, on oxidation with alkaline peroxide, gave the previously reported 7 beta, 8 beta-epoxydihydrocodeinone (22) as the hemimethanol ketal (21). Compound 3 was about ninefold more potent an agonist than dihydrocodeine, and the N-(cyclopropylmethyl)-7 beta, 8 beta-methano compound 19 had moderately potent mixed agonist-narcotic antagonist properties.

  DOI：

  10.1021/jm00138a016