4,5α-epoxy-8β-<(hydroxyethyl)thio>-3-methoxy-17-methylmorphinan-6-one | 77794-41-3

• 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: 4,5α-epoxy-8β-<(hydroxyethyl)thio>-3-methoxy-17-methylmorphinan-6-one
• 英文别名: 4,5α-epoxy-8β-[(hydroxyethyl)thio]-3-methoxy-17-methylmorphinan-6-one；(4R,4aR,5S,7aR,12bS)-5-(2-hydroxyethylsulfanyl)-9-methoxy-3-methyl-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one
• CAS: 77794-41-3
• 化学式: C₂₀H₂₅NO₄S
• 分子量: 375.489
• InChiKey: NMFQLKQRGIBSRD-MVHDURJCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  84.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-巯基乙醇 、 可待因酮 在 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.25h， 以100%的产率得到4,5α-epoxy-8β-<(hydroxyethyl)thio>-3-methoxy-17-methylmorphinan-6-one
  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

文献信息

• Analgesic narcotic antagonists. 6. 7.beta.,8.beta.-Methano- and 7.beta.,8.beta.-epoxydihydrocodeinone
  作者：Michael P. Kotick

  DOI：10.1021/jm00138a016

  日期：1981.6

  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.