N-[3',4'-二羟基-(E)-肉桂酰]-3-羟基-L-酪氨酸 | 53755-02-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: N-[3',4'-二羟基-(E)-肉桂酰]-3-羟基-L-酪氨酸
• 中文别名: N- [3'，4'-二羟基-(E)-肉桂酰基] -3-羟基-L-酪氨酸
• 英文名称: (S,E)-3-(3,4-dihydroxyphenyl)-2-(3-(3,4-dihydroxyphenyl)acrylamido)propionic acid
• 英文别名: 3-(3,4-dihydroxy-phenyl)-2-[3-(3,4-dihydroxy-phenyl)-acryloylamino]propionic acid；(-)-N-[3',4'-dihydroxy-(E)-cinnamoyl]-3-hydroxy-L-tyrosine；N-[3',4'-dihydroxy-(E)-cinnamoyl]-3-hydroxy-L-tyrosine；caffeoyl L-DOPA；trans-clovamide；L-clovamide；(2S)-3-(3,4-dihydroxyphenyl)-2-[[(E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]amino]propanoic acid
• CAS: 53755-02-5
• 化学式: C₁₈H₁₇NO₇
• 分子量: 359.335
• InChiKey: GPZFXSWMDFBRGS-UXONFWTHSA-N

物化性质

• 熔点：
  108-112°C
• 溶解度：
  甲醇（微溶）、水（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  147
• 氢给体数：
  6
• 氢受体数：
  7

安全信息

• 储存条件：
  -20°C，密闭保存，干燥环境中存放。

制备方法与用途

丁香酰胺（反式丁香酰胺）是一种天然酚类化合物，也是一种有效的抗氧化剂。克洛维胺则是一种优秀的活性氧和氧自由基清除剂，并且还具有抗炎和神经保护作用。此外，克洛维胺还是一种抗菌剂，能够对抗人类病原体如A型流感H5N1亚型、伊氏锥虫以及幽门螺旋杆菌。

反应信息

• 作为反应物：
  描述：

  N-[3',4'-二羟基-(E)-肉桂酰]-3-羟基-L-酪氨酸 在 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 为溶剂， 反应 9.0h， 以96%的产率得到dihydroclovamide
  参考文献：
  名称：

  氯丁酰胺及其相关化合物抑制淀粉样蛋白β聚集的构效关系。

  摘要：

  阿尔茨海默氏病（AD）是一种神经退行性疾病，其特征是淀粉样β蛋白（Aβ）聚集。Aβ通过β折叠形成聚集，并诱导针对神经元细胞的细胞毒性。因此，天然存在的化合物抑制Aβ聚集是治疗AD的有前途的策略。我们已经报道了具有两个或多个邻苯二酚部分的咖啡酰奎尼酸和苯乙酮类糖苷强烈抑制了Aβ聚集。从可可豆（Theobroma cacao L.）分离的含有两个邻苯二酚部分的环丙酰胺（1）被认为对Aβ聚集具有预防作用。为了研究氯丁酰胺（1）抑制Aβ聚集的构效关系，我们通过1-DOPA，d-DOPA，l-酪氨酸，或l-苯丙氨酸和咖啡酸，对香豆酸或肉桂酸，化合物12和13衍生自1。在测试的化合物1-13中，含有一个或两个邻苯二酚部分的化合物表现出强的抗聚集活性，而非儿茶酚类相关化合物几乎没有活性。这表明至少一个儿茶酚部分对于抑制Aβ42聚集是必不可少的，并且该活性根据儿茶酚部分的数目而增加。因此，clovamid

  DOI：

  10.1016/j.bmc.2018.04.044
• 作为产物：
  描述：

  左旋多巴 在 氯化亚砜 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 84.75h， 生成 N-[3',4'-二羟基-(E)-肉桂酰]-3-羟基-L-酪氨酸
  参考文献：
  名称：

  氯丁酰胺及其相关化合物抑制淀粉样蛋白β聚集的构效关系。

  摘要：

  阿尔茨海默氏病（AD）是一种神经退行性疾病，其特征是淀粉样β蛋白（Aβ）聚集。Aβ通过β折叠形成聚集，并诱导针对神经元细胞的细胞毒性。因此，天然存在的化合物抑制Aβ聚集是治疗AD的有前途的策略。我们已经报道了具有两个或多个邻苯二酚部分的咖啡酰奎尼酸和苯乙酮类糖苷强烈抑制了Aβ聚集。从可可豆（Theobroma cacao L.）分离的含有两个邻苯二酚部分的环丙酰胺（1）被认为对Aβ聚集具有预防作用。为了研究氯丁酰胺（1）抑制Aβ聚集的构效关系，我们通过1-DOPA，d-DOPA，l-酪氨酸，或l-苯丙氨酸和咖啡酸，对香豆酸或肉桂酸，化合物12和13衍生自1。在测试的化合物1-13中，含有一个或两个邻苯二酚部分的化合物表现出强的抗聚集活性，而非儿茶酚类相关化合物几乎没有活性。这表明至少一个儿茶酚部分对于抑制Aβ42聚集是必不可少的，并且该活性根据儿茶酚部分的数目而增加。因此，clovamid

  DOI：

  10.1016/j.bmc.2018.04.044

文献信息

• 迷迭香酸衍生物及其制备方法和应用
  申请人：南宁多灵生物科技有限公司

  公开号：CN110563602A

  公开（公告）日：2019-12-13

  本发明涉及迷迭香酸衍生物及其制备方法，本发明公开的迷迭香酸类似物或含有其药物在临床上可接受的盐，在治疗肝癌、肺癌、直肠癌等肿瘤疾病拥有良好的应用前景。
• Isolation and synthesis of trans- and cis-(−)-clovamides and their deoxy analogues from the bark of Dalbergia melanoxylon
  作者：Fanie R. Van Heerden、E. Vincent Brandt、David G. Roux

  DOI：10.1016/s0031-9422(00)82207-4

  日期：1980.1

  Abstract N -(3′,4′-Dihydroxy- trans -cinnamoyl)-3-(3,4-dihydroxyphenyl)- L -alanine [(−)-clovamide], the major phenolic metabolite (0.1%) in the bark of Dalbergia melanoxylon , is associated with minor proportions of its cis -isomer, and similar pairs of geometrical isomers of their deoxy analogues N -(4′-hydroxycinnamoyl)-3-(3,4-dihydroxyphenyl)- L -alanine and N -(4′-hydroxycinnamoyl)-3-(4-hydroxyphenyl)-

  摘要 N -(3',4'-Dihydroxy-trans-cinnamoyl)-3-(3,4-dihydroxyphenyl)-L-丙氨酸 [(-)-clovamide]，树皮中的主要酚类代谢物 (0.1%) Dalbergia melanoxylon 与其脱氧类似物 N -(4'-羟基肉桂酰基)-3-(3,4-二羟基苯基)- L -丙氨酸和 N -( 4'-羟基肉桂酰基)-3-(4-羟基苯基)-L-丙氨酸。(-)- 反式-氯洛酰胺是通过咖啡酸的酰氯与左旋多巴直接缩合合成的。记录了这些化合物的诊断 CD 谱和 (-)-反式和 (-)- 顺式氯洛酰胺的 13 C 谱。
• Genetically altered alfalfa producing clovamide and/or related hydroxycinnamoyl amides
  申请人：The United States of America, as represented by the Secretary of Agriculture

  公开号：US10253324B2

  公开（公告）日：2019-04-09

  Two novel cDNAs for two different genes, HDT1 and HDT2, are isolated from red clover and sequenced. Both HDT1 and HDT2 encode hydroxycinnamoyl-CoA:L-DOPA/tyrosine hydroxycinnamoyl transferase (HDT) which enzymatically produces clovamide and/or related hydroxycinnamoyl amides. Clovamide and related hydroxycinnamoyl amides reduce post-harvest protein degradation. Genetically altered alfalfa plants containing an expression cassette containing a cDNA encoding HDT1 or HDT2 are generated. These genetically altered alfalfa plants produce hydroxycinnamoyl-CoA:L-DOPA/tyrosine hydroxycinnamoyl transferase, which in turn produces clovamide and/or related hydroxycinnamoyl amides.

  从红三叶中分离出两个不同基因 HDT1 和 HDT2 的新型 cDNA，并对其进行了测序。HDT1 和 HDT2 都编码羟基肉桂酰-CoA:L-DOPA/酪氨酸羟基肉桂酰转移酶（HDT），它能酶促产生氯酰胺和/或相关的羟基肉桂酰酰胺。氯酰胺和相关的羟基肉桂酰酰胺可减少收获后蛋白质的降解。基因改变的苜蓿植株含有一个表达盒，其中包含编码 HDT1 或 HDT2 的 cDNA。这些基因改变的苜蓿植物会产生羟基肉桂酰-CoA:L-DOPA/酪氨酸羟基肉桂酰转移酶，进而产生氯酰胺和/或相关的羟基肉桂酰酰胺。
• The structure–activity relationship of the series of non-peptide small antagonists for p56lck SH2 domain
  作者：See-Hyoung Park、Hyun-Sik Oh、Mi-Ae Kang、Hyeongjin Cho、Joshi Bishnu Prasad、Jonghwa Won、Keun-Hyeung Lee

  DOI：10.1016/j.bmc.2006.06.059

  日期：2007.6.1

  The antagonists for the SH2 domain are regarded as novel therapeutic candidates for cancer, autoimmune disease, and chronic inflammatory disease. Previously, we identified rosmarinic acid (alpha-o-caffeoyl-3,4-dihydroxyphenyl-lactic acid; RosA) from Prunella vulgaris as an antagonist for the p56lck SH2 domain by screening natural products. RosA not containing phosphotyrosine surrogate had a considerable inhibitory activity for T-cell antigen receptor (TCR)-induced interleukin (IL)-2 expression, and subsequent T-cell proliferation in vitro cell assay. To investigate the structure-activity relationship of RosA and to identify a novel p56lck SH2 antagonist with more potent in vitro T-cell inhibitory activity, we synthesized several analogs of RosA by using rational design. All synthesized compounds were tested in vitro binding activity for the SH2 domain and in vitro T-cell inhibitory activity. All four hydroxyl groups of RosA were essential for binding with the p56lck SH2 domain and T-cell inhibitory activity. Unexpectedly, conformationally less constrained analogs 4 and 9 showed a more potent binding affinity for the SH2 domain than that of RosA, and chirality of the analog did not play an important role in protein binding. We successfully identified several RosA analogs with a more potent T-cell inhibitory activity than that of RosA. Overall results revealed important structural requirements of the p56lck SH2 antagonists for in vitro T-cell inhibitory activity and in vitro protein binding activity. (C) 2006 Elsevier Ltd. All rights reserved.
• Isolation, Structure Determination, Synthesis, and Sensory Activity of <i>N</i>-Phenylpropenoyl-<scp>l</scp>-amino Acids from Cocoa (<i>Theobroma cacao</i>)
  作者：Timo Stark、Thomas Hofmann

  DOI：10.1021/jf050458q

  日期：2005.6.1

  Application of chromatographic separation and taste dilution analyses recently revealed besides procyanidins a series of N-phenylpropenoyl amino acids as the key contributors to the astringent taste of nonfermented cocoa beans as well as roasted cocoa nibs. Because these amides have as yet not been reported as key taste compounds, this paper presents the isolation, structure determination, and sensory activity of these amino acid amides. Besides the previously reported (-)-N-[3',4'-dihydroxy-(E)-cinnamoyl]-3-hydroxy-L-tyrosine (clovamide), (-)-N-[4'-hydroxy-(E)-cinnamoyl]-L-tyrosine (deoxyclovamide), and (-)-N-[3',4'-dihydroxy-(E)-cinnamoyl]-L-tyrosine, seven additional amides, namely, (+)-N-[3',4'-dihydroxy-(E)-cinnamoyl]-L-aspartic acid, (+)-N-[4'-hydroxy-(E)-cinnamoyl]-L-aspartic acid, (-)-N-[3',4'-dihydroxy-(E)-cinnamoyl]-L-glutamic acid, (-)-N-[4'-hydroxy-(E)-cinnamoyl]-L-glutamic acid, (-)-N-[4'-hydroxy-(E)-cinnamoyl]-3-hydroxy-L-tyrosine, (+)-N-[4'-hydroxy-3'-methoxy-(E)-cinnamoyl]-L-aspartic acid, and (+)-N-[(E)-cinnamoyl]-L-aspartic acid, were identified for the first time in cocoa products by means of LC-MS/MS, 1D/2D-NMR, UV-vis, CID spectroscopy, and polarimetry, as well as independent enantiopure synthesis. Using the recently developed half-tongue test, human recognition thresholds for the astringent and mouth-drying oral sensation were determined to be between 26 and 220 mu mol/L (water) depending on the amino acid moiety. In addition, exposure to light rapidly converted these [E]-configured N-phenylpropenoyl amino acids into the corresponding [2]-isomers, thus indicating that analysis of these compounds in food and plant materials needs to be performed very carefully in the absence of light to prevent artifact formation.