nabilone methyl ether | 132436-86-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并吡喃类
• 英文名称: nabilone methyl ether
• 英文别名: (6aR,10aR)-(-)-1-Methoxy-3-(1,1-dimethylheptyl)-6,6a,7,8,10,10a-hexahydro-6,6-dimethyl-9H-dibenzopyran-9-one；(6aR,10aR)-3-(1,1-Dimethyl-heptyl)-1-methoxy-6,6-dimethyl-6,6a,7,8,10,10a-hexahydro-benzo[c]chromen-9-one；(6aR,10aR)-1-methoxy-6,6-dimethyl-3-(2-methyloctan-2-yl)-7,8,10,10a-tetrahydro-6aH-benzo[c]chromen-9-one
• CAS: 132436-86-3
• 化学式: C₂₅H₃₈O₃
• 分子量: 386.575
• InChiKey: OSWZVICHJWTZBE-WOJBJXKFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  nabilone methyl ether 在 丙烷-1-硫醇 、 sodium hydride 作用下， 生成 nabilone
  参考文献：
  名称：

  Synthesis of both enantiomers of nabilone from a common intermediate. Enantiodivergent synthesis of cannabinoids

  摘要：

  Both enantiomers of the synthetic cannabinoid nabilone (4) have been synthesized from a common intermediate, enone 7. Enone 7 was prepared by reaction of [2,6-dimethoxy-4-(1,1-dimethylheptyl)phenyl]lithium with (+)-apoverbenone (2), followed by PDC oxidation. Li/NH3 reduction of 7 gave saturated ketone 9, which, after ether cleavage to 10, afforded (6aS,10aR)-hexahydrodibenzopyran 15 on reaction with SnCl4. Isomerization to 6aR,10aR ketone 16 followed by ether cleavage gave the 6aR,10aR enantiomer of nabilone (4). The 6aS,10aS enantiomer of 4 (24) was prepared from 7 by ether cleavage to 18 and rearrangement to nonracemic tetrahydrodibenzopyran 20 using AlCl3. Dissolving metal reduction of 20 followed by ether cleavage gave the 6aS,10aS enantiomer of nabilone (24). A model sequence employing (2,6-dimethoxyphenyl)lithium at the first step was carried out and the structure of one of the intermediates, ketone 12, was established by X-ray crystallography. A new preparation of apoverbenone (2) has been developed.

  DOI：

  10.1021/jo00006a021
• 作为产物：
  描述：

  (-)-4-<2-Hydroxy-4-(1,1-dimethylheptyl)-6-methoxyphenyl>-6,6a-dimethylbicyclo<3.3.1>hept-3-en-2-one 在 三氯化铝 、 jones' reagent 、 氨 、 四氯化锡 、 lithium 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 生成 nabilone methyl ether
  参考文献：
  名称：

  Synthesis of both enantiomers of nabilone from a common intermediate. Enantiodivergent synthesis of cannabinoids

  摘要：

  Both enantiomers of the synthetic cannabinoid nabilone (4) have been synthesized from a common intermediate, enone 7. Enone 7 was prepared by reaction of [2,6-dimethoxy-4-(1,1-dimethylheptyl)phenyl]lithium with (+)-apoverbenone (2), followed by PDC oxidation. Li/NH3 reduction of 7 gave saturated ketone 9, which, after ether cleavage to 10, afforded (6aS,10aR)-hexahydrodibenzopyran 15 on reaction with SnCl4. Isomerization to 6aR,10aR ketone 16 followed by ether cleavage gave the 6aR,10aR enantiomer of nabilone (4). The 6aS,10aS enantiomer of 4 (24) was prepared from 7 by ether cleavage to 18 and rearrangement to nonracemic tetrahydrodibenzopyran 20 using AlCl3. Dissolving metal reduction of 20 followed by ether cleavage gave the 6aS,10aS enantiomer of nabilone (24). A model sequence employing (2,6-dimethoxyphenyl)lithium at the first step was carried out and the structure of one of the intermediates, ketone 12, was established by X-ray crystallography. A new preparation of apoverbenone (2) has been developed.

  DOI：

  10.1021/jo00006a021

文献信息

• 3-(1′,1′-Dimethylbutyl)-1-deoxy-Δ8-THC and related compounds: synthesis of selective ligands for the CB2 receptor
  作者：John W. Huffman、John Liddle、Shu Yu、Mie Mie Aung、Mary E. Abood、Jenny L. Wiley、Billy R. Martin

  DOI：10.1016/s0968-0896(99)00219-9

  日期：1999.12

  and CB2 receptors were determined employing previously described procedures. Five of the 3-(1',1'-dimethylalkyl)-1-deoxy-delta8-THC analogues (2, n = 1-5) have high affinity (Ki = < 20 nM) for the CB2 receptor. Four of them (2, n = 1-4) also have little affinity for the CB1 receptor (Ki = > 295 nM). 3-(1',1'-Dimethylbutyl)-1-deoxy-delta8-THC (2, n = 2) has very high affinity for the CB2 receptor (Ki

  描述了15个1-deoxy-delta8-THC类似物的合成和药理作用，其中一些对CB2受体具有高亲和力。所述脱氧大麻素包括1-脱氧-11-羟基-δ8-THC（5），1-脱氧δ8-THC（6），1-脱氧-3-丁基-δ8-THC（7），1-脱氧-3 -hexyl-delta8-THC（8）和一系列3-（1'，1'-二甲基烷基）-1-deoxy-delta8-THC类似物（2，n = 0-4，6，7，其中n =侧链中的碳原子数-2）。还制备了脱氧萘丁酮（16）的三种衍生物（17-19）。使用前述方法确定每种化合物对CB1和CB2受体的亲和力。3-（1'，1'-二甲基烷基）-1-脱氧-delta8-THC类似物中的五个（2，n = 1-5）对CB2受体具有高亲和力（Ki = <20 nM）。其中四个（2，n = 1-4）对CB1受体的亲和力也很小（Ki => 295 nM）。3-（1'，1'-二
• Preparation of 6a,10a-trans-hexahydrodibenzopyranones
  申请人：Eli Lilly and Company

  公开号：US04395560A1

  公开（公告）日：1983-07-26

  Reaction of an O-methyl or O-ethyl resorcinol with a cyclohexene carbinol derivative in the presence of a catalyst affords a 6a,10a-trans-1-methoxy or 1-ethoxy-6,6-dimethyl-6,6a,7,8,10,10a-hexahydro-9H-dibenzo[b,d]pyran-9-one derivative.

  在催化剂的存在下，O-甲基或O-乙基邻苯二酚与环己烯醇衍生物反应，得到6a,10a-顺式-1-甲氧基或1-乙氧基-6,6-二甲基-6,6a,7,8,10,10a-六氢-9H-二苯并[b,d]吡喃-9-酮衍生物。
• Preparation of 6a, 10a-trans-hexahydrodibenzopyranones
  申请人：ELI LILLY AND COMPANY

  公开号：EP0096480A2

  公开（公告）日：1983-12-21

  Reaction of an 0-methyl or O-ethyl resorcinol with a cyclohexene carbinol derivative in the presence of a catalyst affords a 6a,10a-trans-1-methoxy or 1-ethoxy-6,6-dimethyl-8,6a,7,8.10,10a-hexahydro-9H-dibenzo[b,d]pyran-9-one derivative. Optional deesterification of the product affords the corresponding 1-hydroxy compound.

  在催化剂存在下，0-甲基或 O-乙基间苯二酚与环己烯甲醇衍生物反应，生成 6a,10a-反式-1-甲氧基或 1-乙氧基-6,6-二甲基-8,6a,7,8.10,10a-六氢-9H-二苯并[b,d]吡喃-9-酮衍生物。可选择对产物进行脱酯化处理，得到相应的 1-羟基化合物。
• HUFFMAN, JOHN W.;JOYNER, H. HOWARD;LEE, MELISSA D.;JORDAN, ROBERT D.;PENN+, J. ORG. CHEM., 56,(1991) N, C. 2081-2086
  作者：HUFFMAN, JOHN W.、JOYNER, H. HOWARD、LEE, MELISSA D.、JORDAN, ROBERT D.、PENN+

  DOI：——

  日期：——
• US4395560A
  申请人：——

  公开号：US4395560A

  公开（公告）日：1983-07-26