3-O-(tert-butyldimethylsilyl)-4,5α-epoxy-3,6α,14-trihydroxy-17-(cyclopropylmethyl)morphinan | 124154-49-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: 3-O-(tert-butyldimethylsilyl)-4,5α-epoxy-3,6α,14-trihydroxy-17-(cyclopropylmethyl)morphinan
• 英文别名: 3-O-t-butyldimethylsilyl-6α-naltrexol
• CAS: 124154-49-0
• 化学式: C₂₆H₃₉NO₄Si
• 分子量: 457.685
• InChiKey: VBNIQPXWLIPZLQ-FSTJURTJSA-N

物化性质

• 沸点：
  550.3±50.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.0
• 重原子数：
  32.0
• 可旋转键数：
  4.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  62.16
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  3-O-(tert-butyldimethylsilyl)-4,5α-epoxy-3,6α,14-trihydroxy-17-(cyclopropylmethyl)morphinan 在 SO₃H silica gel 作用下， 反应 2.0h， 以95%的产率得到6alpha-Naltrexol
  参考文献：
  名称：

  Application of SO3H Silica Gel to Deprotection of Silyl Ethers

  摘要：

  A newly developed SO3H silica gel cleaved the O-Si bonds in various aryl and alkyl silyl ethers to give the corresponding phenols and alcohols in good to excellent yield. The crude filtrates contained no silyl residues. The solid phase Si-29 NMR analyses of the SO3H silica gel strongly suggested that the silyl residues were captured by silanol groups on the surface of the silica gel. The SO3H silica gel could be recycled at least ten times without any loss of activity. The disappearance of silyl residues in the crude filtrate was observed in even the 10th repetition. Our method provides an easily handled desilylation method that requires no further purification. Our method was also applicable to a selective desilylation reaction of a derivative 5 with different siloxy groups or desilylation of an alkaloid derivative 7.

  DOI：

  10.3987/com-12-12577
• 作为产物：
  描述：

  3-O-(tert-butyldimethylsilyl)naltrexone 在 L-Selectride 作用下， 以 四氢呋喃 为溶剂， 反应 0.42h， 以82%的产率得到3-O-(tert-butyldimethylsilyl)-4,5α-epoxy-3,6α,14-trihydroxy-17-(cyclopropylmethyl)morphinan
  参考文献：
  名称：

  结合阿片拮抗剂的加成配体。6α-和6β-纳曲醇的甲基丙烯酸酯和醚。

  摘要：

  将α-和β-纳曲醇衍生的酯9和10以及醚11和12分别包含α，β-不饱和酯官能度，制备为螺-α-亚甲基-γ-内酯5和6的构象更灵活的类似物。所有在对[3H]溴唑胺的阿片类药物受体结合试验中具有活性，对[3H] DAGO的活性更强，表明具有mu亚型选择性，但只有醚12表现出显着的不可逆活性。我们得出结论，在非常密切相关的亲电阿片类药物中进行的小结构变化会导致受体结合的变化。这四种化合物都是小鼠中吗啡的长效拮抗剂，酯10与纳曲酮大致等效。

  DOI：

  10.1021/jm00164a043

文献信息

• Design, synthesis, and structure–activity relationship of novel opioid κ-agonists
  作者：Koji Kawai、Jun Hayakawa、Toru Miyamoto、Yoshifumi Imamura、Shinichi Yamane、Hisanori Wakita、Hideaki Fujii、Kuniaki Kawamura、Hirotoshi Matsuura、Naoki Izumimoto、Ryosuke Kobayashi、Takashi Endo、Hiroshi Nagase

  DOI：10.1016/j.bmc.2008.09.011

  日期：2008.10

  By focusing on 4,5-epoxymorphinan, a traditional opioid skeleton but a new structure in the opioid kappa-agonist research field, and by rationally applying the 'message-address concept' and 'accessory site hypothesis,' we discovered a new chemical class opioid kappa- gonist, TRK-820 (1). Its development as an antipruritus is now in the final stage. Here, the full scope of its design, synthesis, and structure-activity relationship are described. (C) 2008 Elsevier Ltd. All rights reserved.