ethyl (2S,3R,4'R,4a'S,7a'R,12b'S)-3'-(cyclopropylmethyl)-4a'-hydroxy-9'-methoxy-2',3',4',4a',5',6'-hexahydro-1'H,7a'H-spiro[oxirane-2,7'-[4,12]methanobenzofuro[3,2-e]isoquinoline]-3-carboxylate | 1186028-93-2

• 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: ethyl (2S,3R,4'R,4a'S,7a'R,12b'S)-3'-(cyclopropylmethyl)-4a'-hydroxy-9'-methoxy-2',3',4',4a',5',6'-hexahydro-1'H,7a'H-spiro[oxirane-2,7'-[4,12]methanobenzofuro[3,2-e]isoquinoline]-3-carboxylate
• CAS: 1186028-93-2
• 化学式: C₂₅H₃₁NO₆
• 分子量: 441.524
• InChiKey: KUAPTDJZMCLPBZ-QITVBBABSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.96
• 重原子数：
  32.0
• 可旋转键数：
  5.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  80.76
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  ethyl (2S,3R,4'R,4a'S,7a'R,12b'S)-3'-(cyclopropylmethyl)-4a'-hydroxy-9'-methoxy-2',3',4',4a',5',6'-hexahydro-1'H,7a'H-spiro[oxirane-2,7'-[4,12]methanobenzofuro[3,2-e]isoquinoline]-3-carboxylate 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以94%的产率得到(3'R,5R,6S,9R,13S,14S)-17-(cyclopropylmethyl)-4,5-epoxy-3'-hydroxymethyl-3-methoxyspiro[morphinane-6,2'-oxirane]-14-ol
  参考文献：
  名称：

  4,5α-环氧吗啡喃衍生物与氨基甲酰基环氧环的重排提供了新的氧杂三环癸烷结构

  摘要：

  我们描述了氨基甲酰环氧4,5α-环氧吗啡喃衍生物的重排，该衍生物通过氧杂双环[2.2.2]辛烷中间体提供具有氧杂三环癸烷结构的新型4,5α-环氧吗啡喃衍生物。我们基于在不同去质子化条件下观察到的结果提出了重排反应的机理。差向异构在重排过程中发生在可逆但不可逆的去质子化条件下。重排产物具有对阿片样物质受体具有中等亲和力的新颖基本结构（K i（μ）= 47.7 nM，K i（δ）= 174.6 nM和K i（κ）= 248.1 nM）。因此，重排产物作为阿片样物质配体可能具有高效力。

  DOI：

  10.1016/j.tet.2011.04.097
• 作为产物：
  描述：

  纳曲酮EP杂质J 、 氯乙酸乙酯 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 以48%的产率得到ethyl (2S,3R,4'R,4a'S,7a'R,12b'S)-3'-(cyclopropylmethyl)-4a'-hydroxy-9'-methoxy-2',3',4',4a',5',6'-hexahydro-1'H,7a'H-spiro[oxirane-2,7'-[4,12]methanobenzofuro[3,2-e]isoquinoline]-3-carboxylate
  参考文献：
  名称：

  Drug design and synthesis of a novel κ opioid receptor agonist with an oxabicyclo[2.2.2]octane skeleton and its pharmacology

  摘要：

  A conformational analysis of kappa opioid receptor agonists, TRK-820 and U-50,488H indicated an active conformation of TRK-820 in which the C-ring was in the boat form with the 14-OH interacting with the amide nitrogen. Based on the obtained active conformation of TRK-820, we designed and synthesized a novel kappa agonist KNT-63 with oxabicyclo[2.2.2]octane skeleton. KNT-63 showed profound antinociceptive effects via the kappa receptor which were as potent as that of TRK-820. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.11.027

文献信息

• Novel Delta Opioid Receptor Agonists with Oxazatricyclodecane Structure
  作者：Hideaki Fujii、Kohei Hayashida、Akiyoshi Saitoh、Akinobu Yokoyama、Shigeto Hirayama、Takashi Iwai、Eriko Nakata、Toru Nemoto、Yuka Sudo、Yasuhito Uezono、Mitsuhiko Yamada、Hiroshi Nagase

  DOI：10.1021/ml400491k

  日期：2014.4.10

  We synthesized compounds 4a,c-f,h,i containing the oxazatricyclodecane structure from a novel rearrangement reaction product 2a. All the prepared compounds 4a,c-f,h,i exhibited full agonistic activities for the delta opioid receptor (DOR). Among them, the N-methyl derivative 4c was highly selective, and the most effective DOR agonist in functional assays. Subcutaneous administration of 4c produced dose-dependent and NTI (selective DOR antagonist)-reversible antinociception lacking any convulsive behaviors in the mice acetic acid writhing tests. The N-methyl derivative 4c is expected to be a promising lead compound for selective DOR agonists with a novel chemotype.