N-苄基-(9Z,12Z)-十八碳二烯酰胺 | 18286-71-0

• 物质功能分类: 生物化工 - 提取物 - 植物提取物
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: N-苄基-(9Z,12Z)-十八碳二烯酰胺
• 英文名称: (9Z,12Z)-N-benzyloctadeca-9,12-dienamide
• 英文别名: N-benzyl-9,12-(9Z,12Z)-octadecadienamide；N-benzyl-(9Z,12Z)-octadecadienamide；N-benzy1-9Z, 12Z-octadecadienamide；N-benzyloctadec-9Z,12Z-dienamide；N-benzyllinoleamide；N-Benzyl-linoleamid；N-Benzyl-linoleamide
• CAS: 18286-71-0
• 化学式: C₂₅H₃₉NO
• 分子量: 369.591
• InChiKey: YJWLCIANOBCQGW-HZJYTTRNSA-N

物化性质

• 沸点：
  534.2±39.0 °C(Predicted)
• 密度：
  0.933±0.06 g/cm3(Predicted)
• 溶解度：
  DMF:30.0(最大浓度 mg/mL);81.17(最大浓度 mM)DMSO:30.0(最大浓度 mg/mL);81.17(最大浓度 mM)乙醇:30.0(最大浓度 mg/mL);81.17(最大浓度 mM)
• 保留指数：
  3063.6

计算性质

• 辛醇/水分配系数(LogP)：
  7.8
• 重原子数：
  27
• 可旋转键数：
  16
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  室温

制备方法与用途

生物活性

N-苯基-（9Z,12Z）-十八碳二烯酰胺是从玛卡（Lepidium meyenii Walp.）中分离出来的，具有抗运动性疲劳的药理作用。

化学性质

该化合物为淡黄色粘稠状物质，可以溶解于甲醇、乙醇和DMSO等有机溶剂中。它来源于玛卡（Lepidium meyenii Walp.）植物。

用途

N-苄基-(9Z,12Z)-十八碳二烯酰胺具有多种药理作用，包括增强精力、提高生育力、改善性功能、治疗更年期综合症、风湿症和抑郁症等。

反应信息

• 作为产物：
  描述：

  (Z,Z)-9,12-十八烷二烯酸二聚物 、 苄胺 在 N,N'-二环己基碳二亚胺 、 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 12.25h， 以50%的产率得到N-苄基-(9Z,12Z)-十八碳二烯酰胺
  参考文献：
  名称：

  作为 TNF-α 抑制剂的 macamides 文库的合成和生物筛选

  摘要：

  通过修改初始分子结构合成了 35 个 macamide 类似物。使用NMR和MS确认所得结构。在 THP-1 细胞系中评估了这些合成 macamides 的细胞毒性和抗炎活性。初步生物学评估表明，与对照（放线菌素 D）相比，这些合成的 macamides 中的大多数在测试细胞系中不存在细胞毒性（MTT 测定）。关于抗炎活性，一些类似物比天然马酰胺具有更大的抑制 TNF-α 的潜力。合成的 macamide 4a是最活跃的 (IC 50= 0.009 ± 0.001 μM) 与 C87（对照）相比。通过观察化学结构和活性之间的联系，我们的研究证明了天然大麦酰胺在烷基链、苄基位置、酰胺键以及在芳环上添加两个甲基的水平发生了变化（元位置）引导我们获得具有更大抗炎活性的新macamides。

  DOI：

  10.1039/d0md00208a

文献信息

• Synthesis and Biological Evaluation of Macamides Derivatives as Potent Inhibitors of Breast Cancer Cell MCF-7
  作者：Xiao Xia Liang、Cheng Xiong、Min He、Changliang He、Zhongqiong Yin

  DOI：10.2174/1570180813888160201100814

  日期：2016.6.18

  macamides (1-4) and their synthetic analogs (5-14) were synthesized and evaluated for in vitro inhibitory activities against breast cancer cell MCF-7. The results of bioactive assay showed that two of the macamides (compound 1 and 4) and one synthetic analog (compound 5) displayed comparable inhibitory activities against MCF-7 cell line, with IC50 values of 29.6, 36.2 and 27.2 µM, respectively.

  合成了一系列的甲酰胺（1-4）及其合成类似物（5-14），并评估了其对乳腺癌细胞MCF-7的体外抑制活性。生物活性分析的结果表明，其中的两种酰胺（化合物1和4）和一种合成的类似物（化合物5）对MCF-7细胞系表现出相当的抑制活性，IC 50值分别为29.6、36.2和27.2 µM。
• 一种玛咖酰胺的合成方法及其用途
  申请人：中国科学院过程工程研究所

  公开号：CN104513171B

  公开（公告）日：2017-09-01

  本发明涉及一种玛咖酰胺的合成方法，所述方法为：以脂肪酸，和苄胺或间甲氧基苄胺为反应原料，在已经溶解有HOAt、EDC·HCl及DIPEA的二氯甲烷溶液中混合，搅拌进行反应，然后将反应产物水洗，将水不溶物干燥即得玛咖酰胺。本发明所述合成玛咖酰胺的方法，步骤简单，原料易得，操作条件易控，产物无需纯化纯度即可达95%以上；为工业化合成玛咖酰胺提供了基础；另外，本发明合成的玛咖酰胺具有提高男性生育能力和治疗男性性功能障碍的作用，为玛咖酰胺的应用提供了市场前景。
• The Efficient Synthesis and Anti-Fatigue Activity Evaluation of Macamides: The Unique Bioactive Compounds in Maca
  作者：Tao Liu、Ziyan Peng、Wei Lai、Yan Shao、Qing Gao、Miaoxin He、Wan Zhou、Lirong Guo、Jiyao Kang、Xiaobao Jin、Hui Yin

  DOI：10.3390/molecules28093943

  日期：——

  Macamides are a class of amide alkaloids that are only found in maca and are widely considered to be its bioactive marker compounds. More than thirty macamide monomers have been identified in recent years; however, it is difficult to obtain a single macamide monomer from the maca plant because of their similar structures and characteristics. We used the carbodiimide condensation method (CCM) to efficiently synthesize five typical macamides, including N-benzyl-hexadecanamide (NBH), N-benzyl-9Z,12Z,15Z-octadecenamide, N-(3-methoxybenzyl)-9Z,12Z-octadecenamide, N-benzyl-9Z,12Z-octadecenamide, and N-(3-methoxybenzyl)-9Z,12Z,15Z-octadecadienamide. All the synthesized macamides were purified by a one-step HPLC with a purity of more than 95%. NBH is the most abundant macamide monomer in natural maca, and it was selected to evaluate the anti-fatigue effects of macamides. The results indicated that NBH could enhance the endurance capacity of mice by increasing liver glycogen levels and decreasing blood urea nitrogen, lactate dehydrogenase, blood ammonia, and blood lactic acid levels. Macamides might be the active substances that give maca its anti-fatigue active function.

  玛卡酰胺是一类酰胺生物碱，只存在于玛卡中，被广泛认为是玛卡的生物活性标志化合物。近年来已发现三十多种玛卡酰胺单体，但由于其结构和特性相似，很难从玛卡植物中获得单一的玛卡酰胺单体。我们采用碳二亚胺缩合法（CCM）高效合成了五种典型的马卡酰胺，包括 N-苄基十六酰胺（NBH）、N-苄基-9Z,12Z,15Z-辛酰胺（NBH）、N-苄基-9Z,12Z,15Z-辛酰胺（NBH）、N-苄基-9Z,12Z,15Z-辛酰胺（NBH12Z,15Z-十八烯酰胺、N-(3-甲氧基苄基)-9Z,12Z-十八烯酰胺、N-苄基-9Z,12Z-十八烯酰胺和 N-(3-甲氧基苄基)-9Z,12Z,15Z-十八烯酰胺。所有合成的大酰胺均通过一步高效液相色谱法纯化，纯度超过 95%。NBH是天然玛咖中含量最高的玛酰胺单体，因此被选来评估玛酰胺的抗疲劳作用。结果表明，NBH能提高肝糖原水平，降低血尿素氮、乳酸脱氢酶、血氨和血乳酸水平，从而增强小鼠的耐力。玛卡酰胺可能是赋予玛卡抗疲劳活性功能的活性物质。
• Macamides and their synthetic analogs: Evaluation of in vitro FAAH inhibition
  作者：Hui Wu、Charles J. Kelley、Alejandro Pino-Figueroa、Huyen D. Vu、Timothy J. Maher

  DOI：10.1016/j.bmc.2013.06.034

  日期：2013.9

  Maca (Lepidium meyenii), a traditional food crop of the Peruvian Andes is now widely touted as a dietary supplement. Among the various chemical constituents isolated from the plant are a unique series of non-polar, long-chain fatty acid N-benzylamides known as macamides. We have synthesized 11 of the 19 reported macamides and have tested each as potential inhibitors of the human enzyme, fatty acid amide hydrolase (FAAH). The five most potent macamides were FAAH inhibitors (IC50 = 10-17 mu M). These amides were derivatives of oleic, linoleic and linolenic acids and benzylamine or 3-methoxybenzylamine. Of the three compounds evaluated in a pre-incubation time study, two macamides were not irreversible inhibitors of FAAH. The third, a carbamate structurally related to macamides, was shown to be an irreversible inhibitor of FAAH (IC50 = 0.153 mu M). (C) 2013 Elsevier Ltd. All rights reserved.
• <i>N</i>-Benzyl-linoleamide, a Constituent of <i>Lepidium meyenii</i> (Maca), Is an Orally Bioavailable Soluble Epoxide Hydrolase Inhibitor That Alleviates Inflammatory Pain
  作者：Nalin Singh、Bogdan Barnych、Christophe Morisseau、Karen M. Wagner、Debin Wan、Ashley Takeshita、Hoang Pham、Ting Xu、Abhaya Dandekar、Jun-Yan Liu、Bruce D. Hammock

  DOI：10.1021/acs.jnatprod.0c00938

  日期：2020.12.24

  Lepidium meyenii (maca), a plant indigenous to the Peruvian Andes, recently has been utilized globally for claimed health or recreational benefits. The search for natural products that inhibit soluble epoxide hydrolase (sEH), with therapeutically relevant potencies and concentrations, led to the present study on bioactive amide secondary metabolites found in L. meyenii, the macamides. Based on known and suspected macamides, 19 possible macamides were synthesized and characterized. The majority of these amides displayed excellent inhibitory potency (IC₅₀ ≈ 20-300 nM) toward the recombinant mouse, rat, and human sEH. Quantitative analysis of commercial maca products revealed that certain products contain known macamides (1-5, 8-12) at therapeutically relevant total concentrations (≥3.29 mg/g of root), while the inhibitory potency of L. meyenii extracts directly correlates with the sum of concentration/IC₅₀ ratios of macamides present. Considering both its in vitro efficacy and high abundance in commercial products, N-benzyl-linoleamide (4) was identified as a particularly relevant macamide that can be utilized for in vivo studies. Following oral administration in the rat, compound 4 not only displayed acceptable pharmacokinetic characteristics but effectively reduced lipopolysaccharide-induced inflammatory pain. Inhibition of sEH by macamides provides a plausible biological mechanism of action to account for several beneficial effects previously observed with L. meyenii treatments.