methyl 12-phenylacetylricinoleate | 1108200-40-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: methyl 12-phenylacetylricinoleate
• 英文别名: methyl (Z,12R)-12-(2-phenylacetyl)oxyoctadec-9-enoate
• CAS: 1108200-40-3
• 化学式: C₂₇H₄₂O₄
• 分子量: 430.628
• InChiKey: UMUBCAKMIIRYES-ILGCSIJVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.2
• 重原子数：
  31
• 可旋转键数：
  20
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 12-phenylacetylricinoleate 在 Novozym 435 、 水 作用下， 以 丙酮 为溶剂， 反应 1.0h， 以99%的产率得到12-phenylacetyltricinoleic acid
  参考文献：
  名称：

  Chemoenzymatic synthesis and cannabinoid activity of a new diazabicyclic amide of phenylacetylricinoleic acid

  摘要：

  Endocannabinoids (eCBs) are endogenous neuromodulators of synaptic transmission. Their dysfunction may cause debilitating disorders of diverse clinical manifestation. For example, drug addiction, lack of sex desire, eating disorders, such as anorexia or bulimia and dyssomnias. eCBs also participate in the regulation of core temperature and pain perception. In this context, it is important to recognize the utility of cannabinoid receptor 1 (CB1R) agonists, natural as Delta(9)-tetrahydrocannabinol (THC) or synthetic as Nabilone as useful drugs to alleviate this kind of patients' suffering. Therefore, we have developed a new drug, (R,Z)-18-((1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)-18-oxooctadec-9-en-7-yl phenylacetate (PhAR-DBH-Me), that appears to bind and activate the CB1R. This diazabicyclic amide was synthesized from phenylacetylricinoleic acid and (1S, 4S)-2,5-diazabicyclo[ 2.2.1] heptane. To test its cannabinergic properties we evaluated its effects on core temperature, pain perception, and the sleep-waking cycle of rats. Results indicate that 20 and 40 mg/kg of PhAR-DBH-Me readily reduced core temperature and increased pain perception threshold. In addition, 20 mg/kg increased REM sleep in otherwise normal rats. All these effects were prevented or attenuated by AM251, a CB1R antagonist. Place preference conditioning studies indicated that this molecule does not produce rewarding effects. These results strongly support that PhAR-DBH-Me possesses cannabinoid activity without the reinforcement effects. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.04.074
• 作为产物：
  描述：

  苯乙酸 、 蓖麻油酸甲酯 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以88.5%的产率得到methyl 12-phenylacetylricinoleate
  参考文献：
  名称：

  Phenylacetylrinvanil 的高效化学酶法合成：一种超强效辣椒素

  摘要：

  描述了一种超强效辣椒素类物质苯乙酰基苯环 (PhAR) 的直接合成。该过程从通过蓖麻油甲醇分解定量合成蓖麻油酸甲酯 (MeRic) 开始。之后，有两种替代途径是可能的：a) 由南极念珠菌脂肪酶-B (CaLB) 催化 MeRic 的化学选择性香草胺氨解以产生 rinvanil，在与苯乙酸和 DCC-DMAP 反应后进行区域选择性吡咯烷脱酰化产生 PhAR， 51% 的全球收率，b) 通过 MeRic 与苯乙酸和 DCC-DMAP 反应合成 12-苯基乙酰蓖麻油酸甲酯，然后由 CaLB 催化的化学选择性香草胺氨解以获得 PhAR，总收率为 70%。

  DOI：

  10.1055/s-0028-1083521

文献信息

• Chemoenzymatic synthesis and cannabinoid activity of a new diazabicyclic amide of phenylacetylricinoleic acid
  作者：Manuel López-Ortíz、Andrea Herrera-Solís、Axel Luviano-Jardón、Nidia Reyes-Prieto、Ivan Castillo、Ivan Monsalvo、Patricia Demare、Mónica Méndez-Díaz、Ignacio Regla、Oscar Prospéro-García

  DOI：10.1016/j.bmcl.2010.04.074

  日期：2010.6

  Endocannabinoids (eCBs) are endogenous neuromodulators of synaptic transmission. Their dysfunction may cause debilitating disorders of diverse clinical manifestation. For example, drug addiction, lack of sex desire, eating disorders, such as anorexia or bulimia and dyssomnias. eCBs also participate in the regulation of core temperature and pain perception. In this context, it is important to recognize the utility of cannabinoid receptor 1 (CB1R) agonists, natural as Delta(9)-tetrahydrocannabinol (THC) or synthetic as Nabilone as useful drugs to alleviate this kind of patients' suffering. Therefore, we have developed a new drug, (R,Z)-18-((1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)-18-oxooctadec-9-en-7-yl phenylacetate (PhAR-DBH-Me), that appears to bind and activate the CB1R. This diazabicyclic amide was synthesized from phenylacetylricinoleic acid and (1S, 4S)-2,5-diazabicyclo[ 2.2.1] heptane. To test its cannabinergic properties we evaluated its effects on core temperature, pain perception, and the sleep-waking cycle of rats. Results indicate that 20 and 40 mg/kg of PhAR-DBH-Me readily reduced core temperature and increased pain perception threshold. In addition, 20 mg/kg increased REM sleep in otherwise normal rats. All these effects were prevented or attenuated by AM251, a CB1R antagonist. Place preference conditioning studies indicated that this molecule does not produce rewarding effects. These results strongly support that PhAR-DBH-Me possesses cannabinoid activity without the reinforcement effects. (C) 2010 Elsevier Ltd. All rights reserved.
• Efficient Chemoenzymatic Synthesis of Phenylacetylrinvanil: An Ultrapotent Capsaicinoid
  作者：Edmundo Castillo、Ignacio Regla、Patricia Demare、Axel Luviano-Jardón、Agustín López-Munguía

  DOI：10.1055/s-0028-1083521

  日期：——

  synthesis of methyl ricinoleate (MeRic) by ' castor oil methanolysis. Afterwards, two alternative routes are possible: a) chemoselective vanillylamine aminolysis of MeRic catalyzed by Candida antarctica lipase-B (CaLB) to yield rinvanil, which after reaction with phenylacetic acid and DCC-DMAP followed by a regioselectively pyrrolidine deacylation results in PhAR with a 51% global yield, b) methyl 12-phe

  描述了一种超强效辣椒素类物质苯乙酰基苯环 (PhAR) 的直接合成。该过程从通过蓖麻油甲醇分解定量合成蓖麻油酸甲酯 (MeRic) 开始。之后，有两种替代途径是可能的：a) 由南极念珠菌脂肪酶-B (CaLB) 催化 MeRic 的化学选择性香草胺氨解以产生 rinvanil，在与苯乙酸和 DCC-DMAP 反应后进行区域选择性吡咯烷脱酰化产生 PhAR， 51% 的全球收率，b) 通过 MeRic 与苯乙酸和 DCC-DMAP 反应合成 12-苯基乙酰蓖麻油酸甲酯，然后由 CaLB 催化的化学选择性香草胺氨解以获得 PhAR，总收率为 70%。