咖啡酸

咖啡酸
	IUPAC名; 3-(3,4-Dihydroxyphenyl 2-propenoic acid; 3,4-Dihydroxy-cinnamic acid; trans-Caffeate; 3,4-Dihydroxy-trans-cinnamate); (E)-3-(3,4-dihydroxyphenyl)-2-propenoic acid; 3,4-Dihydroxybenzeneacrylicacid; 3-(3,4-Dihydroxyphenyl)-2-propenoic acid; 3-(3,4-二羥苯基)-2-丙烯酸; 3,4-二羥基苯丙烯酸; β-(3,4-二羥苯基)丙烯酸; 3,4-二羥基肉桂酸; 3,4-二羥基肉桂酸; 3,4-二羥基桂皮酸
識別
CAS號	331-39-5 ?
PubChem	689043
ChemSpider	600426
SMILES	O=C(O)\C=C\c1cc(O)c(O)cc1;
InChI	1/C9H8O4/c10-7-3-1-6(5-8(7)11)2-4-9(12)13/h1-5,10-11H,(H,12,13)/b4-2+;
InChIKey	QAIPRVGONGVQAS-DUXPYHPUBE
性質
化學式	C9H8O4
摩爾質量	180.16 g·mol⁻¹
密度	1.478 g/cm³
熔點	223-225 °C
λmax	327 nm
危險性
	GHS危險性符號;
GHS提示詞	Warning
H-術語	H315, H319, H335, H351, H361
P-術語	P201, P202, P261, P264, P271, P280, P281, P302+352, P304+340, P305+351+338, P308+313, P312, P321, P332+313
NFPA 704	1 1 0
相關物質
相關化學品	綠原酸; 奎尼酸
	若非註明，所有數據均出自標準狀態（25 ℃，100 kPa）下。

咖啡酸（英語：Caffeic acid）是一種歸屬於羥基肉桂酸的有機化合物，同時具有酚羥基和丙烯酸兩種官能團結構。因為咖啡酸是生物合成植物生物質及其殘留物的主要組分之一木質素的關鍵中間體，所以它廣泛存在於各種植物中^[2]。它可以在熱水和乙醇中溶解，冷水中微溶。常溫下為黃白色結晶體。

自然中的含量

自然界中，咖啡酸可以在藍桉的樹皮中找到^[3]，也可以在淡水蕨類槐葉苹^[4]或桑黃蘑菇中發現^[5]。

食物中的含量

咖啡酸在咖啡中的含量非常低，僅為0.03毫克/ 100毫升。它是摩洛哥堅果油所含的主要天然酚類之一^[6]，在一些草藥，特別是百里香、鼠尾草和留蘭香中咖啡酸的含量較高（約20mg/100g）。在錫蘭肉桂和八角茴香中的含量約22mg/100g。向日葵種子中的咖啡酸含量較高（8mg/100g），在紅葡萄酒存在一定量的咖啡酸（1.88mg/100ml），蘋果醬，杏和李子中也含有咖啡酸（1mg/100g）。南美州的草藥巴拉圭冬青中也有相當高含量的咖啡酸（基於薄層色譜密度測定^[7]和高效液相色譜法^[8]測得的含量為150mg /100g）。同時也存在於大麥穀物中^[9]。

代謝途徑

生源合成

咖啡酸的生源合成是從綠原酸的香豆酸酯（酯化的側鏈醇）經羥基化產生的。這種羥基化過程產生莽草酸的咖啡酸酯，進而轉化為綠原酸。它是阿魏酸，松柏醇和芥子醇的前體，它們是形成木質素的重要結構單元^[2]。

許多種植物能產生咖啡酸及其衍生物咖啡酸苯乙醇酯^[10]。

生物轉化

咖啡因O-甲基轉移酶是負責將咖啡酸轉化為阿魏酸的酶。咖啡酸和相關的鄰二酚被組織提取物中的鄰二酚氧化酶快速氧化^[11]。

藥理作用

在體外研究和動物模型中發現咖啡酸具有多種潛在的藥理作用，通過氧化機制咖啡酸對人HT-1080纖維肉瘤細胞系中的對癌細胞增殖的抑制作用。^[12] 咖啡酸在體外和活體內都是一種抗氧化劑^[10]。咖啡酸還顯示出免疫調節和抗炎活性，咖啡酸能使黃麴黴毒素產量降低超過95％，優於其他抗氧化劑。研究表明否則觸發黃麴黴產生黃麴毒素的應激氧化可被咖啡酸阻礙。對咖啡酸致癌性的研究具有混合的結果^[13]。一部分研究結果表明它抑制致癌作用，另一部分結果顯示咖啡酸有致癌作用^[13]。對大鼠進行高劑量咖啡酸的口服給藥會引起胃乳頭狀瘤^[13]。在相同的研究中，高劑量包含咖啡酸的組合抗氧化劑則能顯著減少相同種類大鼠結腸腫瘤的生長^[13]。在一些危險物數據表中咖啡酸被列為潛在致癌物，它已被國際癌症研究機構列為2B類致癌物（「可能對人類致癌」）^[14]。一些研究數據顯示，大鼠腸道中的細菌可能改變咖啡酸代謝產物的形成^[15]^[16]。

化學性質

咖啡酸易於自動氧化。穀胱甘肽以及硫醇類化合物（例如半胱氨酸，巰基乙酸或甲琉酚）或抗壞血酸對咖啡酸的褐變和消失具有抑制作用^[17]，咖啡酸的褐變是由鄰二酚被氧化為鄰二醌造成的。在酸性條件下用高碘酸鈉對咖啡酸進行化學氧化會生成具有呋喃結構的二聚體（2,5-（3'，4'-二羥基苯基）四氫呋喃3,4-二羧酸的異構體）^[18]。使用辣根過氧化物酶/過氧化氫的氧化系統能使咖啡酸聚合^[19]。

其他用途

咖啡酸也用於蛋白質的基質輔助激光解吸/電離質譜分析的輔助基質^[20]。

同分異構體

咖啡酸有三個同屬於羥基苯丙烯酸的同分異構體，分別是：

參考文獻

^ Gould, Kevin S.; Markham, Kenneth R.; Smith, Richard H.; Goris, Jessica J. Functional role of anthocyanins in the leaves of Quintinia serrata A. Cunn.. Journal of Experimental Botany. 2000, 51 (347): 1107–1115 [2017-02-05]. PMID 10948238. doi:10.1093/jexbot/51.347.1107. （原始內容存檔於2009-06-03）.
^ ^2.0 ^2.1 Boerjan, Wout; Ralph, John; Baucher, Marie. Ligninbiosynthesis. Annual Review of Plant Biology. 2003, 54: 519–546 [2017-02-05]. PMID 14503002. doi:10.1146/annurev.arplant.54.031902.134938. （原始內容存檔於2021-12-04）.
^ Santos, Sónia A. O.; Freire, Carmen S. R.; Domingues, M. Rosário M.; Silvestre, Armando J. D.; Pascoal Neto, Carlos Pascoal. Characterization of Phenolic Components in Polar Extracts of Eucalyptus globulus Labill. Bark by High-Performance Liquid Chromatography–Mass Spectrometry. Journal of Agricultural and Food Chemistry. 2011, 59 (17): 9386–93. PMID 21761864. doi:10.1021/jf201801q.
^ Choudhary, M. Iqbal; Naheed, Nadra; Abbaskhan, Ahmed; Musharraf, Syed Ghulam; Siddiqui, Hina; Atta-Ur-Rahman. Phenolic and other constituents of fresh water fern Salvinia molesta. Phytochemistry. 2008, 69 (4): 1018–23. PMID 18177906. doi:10.1016/j.phytochem.2007.10.028.
^ Lee, Y.-S.; Kang, Y.-H.; Jung, J.-Y.; Lee, Sanghyun; Ohuchi, Kazuo; Shin, Kuk Hyun; Kang, Il-Jun; Park, Jung Han Yoon; Shin, Hyun-Kyung; Soon, Sung. Protein glycation inhibitors from the fruiting body of Phellinus linteus. Biological & Pharmaceutical Bulletin. October 2008, 31 (10): 1968–1972 [2017-02-04]. PMID 18827365. doi:10.1248/bpb.31.1968. （原始內容存檔於2012-12-19）.
^ ., Z. Charrouf; ., D. Guillaume. Phenols and Polyphenols from Argania spinosa. American Journal of Food Technology. 2007, 2 (7): 679 [2017-02-04]. doi:10.3923/ajft.2007.679.683. （原始內容存檔於2020-10-20）.
^ Determination of Flavonoids, Phenolic Acids, and Xanthines in Mate Tea (Ilex paraguariensis St.-Hil.). [2017-02-04]. doi:10.1155/2013/658596. （原始內容存檔於2019-08-23）.
^ Chemical Composition and Antioxidant Activity of Yerba-Mate (Ilex paraguariensis A.St.-Hil., Aquifoliaceae) Extract as Obtained by Spray Drying. Journal of Analytical Methods in Chemistry. [2017-02-04]. doi:10.1021/jf2008343. （原始內容存檔於2019-12-02）.
^ Quinde-Axtell, Zory; Baik, Byung-Kee. Phenolic Compounds of Barley Grain and Their Implication in Food Product Discoloration. J. Agric. Food Chem. 2006, 54 (26): 9978–9984 [2017-02-04]. PMID 17177530. doi:10.1021/jf060974w. （原始內容存檔於2021-05-06）.
^ ^10.0 ^10.1 Olthof, M. R.; Hollman, P. C.; Katan, M. B. Chlorogenic acid and caffeic acid are absorbed in humans. J. Nutr. January 2001, 131 (1): 66–71 [2017-02-05]. PMID 11208940. （原始內容存檔於2020-06-26）.
^ Pierpoint, W. S. o-Quinones formed in plant extracts. Their reactions with amino acids and peptides. Biochem. J. 1969, 112: 609–616. doi:10.1042/bj1120609.
^ Rajendra Prasad, N.; Karthikeyan, A.; Karthikeyan, S.; Reddy, B. V. Inhibitory effect of caffeic acid on cancer cell proliferation by oxidative mechanism in human HT-1080 fibrosarcoma cell line. Mol Cell Biochem. Mar 2011, 349 (1–2): 11–19. doi:10.1007/s11010-010-0655-7.
^ ^13.0 ^13.1 ^13.2 ^13.3 Hirose, M.; Takesada, Y.; Tanaka, H.; Tamano, S.; Kato, T.; Shirai, T. Carcinogenicity of antioxidants BHA, caffeic acid, sesamol, 4-methoxyphenol and catechol at low doses, either alone or in combination, and modulation of their effects in a rat medium-term multi-organ carcinogenesis model (PDF). Carcinogenesis. 1998, 19 (1): 207–212. PMID 9472713. doi:10.1093/carcin/19.1.207.
^ Agents Classified by the IARC Monographs （頁面存檔備份，存於網際網路檔案館）, International Agency for Research on Cancer
^ Peppercorn, M. A.; Goldman, P. Caffeic acid metabolism by gnotobiotic rats and their intestinal bacteria. Proceedings of the National Academy of Sciences. 1972, 69 (6): 1413–1415 [2017-02-05]. PMC 426714 . PMID 4504351. doi:10.1073/pnas.69.6.1413. （原始內容存檔於2008-08-08）.
^ Gonthier, M.-P.; Verny, M.-A.; Besson, C.; Rémésy, C.; Scalbert, A. Chlorogenic acid bioavailability largely depends on its metabolism by the gut microflora in rats. Journal of Nutrition. 1 June 2003, 133 (6): 1853–1859 [2017-02-05]. PMID 12771329. （原始內容存檔於2009-04-08）.
^ Cilliers, Johannes J. L.; Singleton, Vernon L. Caffeic acid autoxidation and the effects of thiols. J. Agric. Food Chem. 1990, 38 (9): 1789–1796 [2017-02-05]. doi:10.1021/jf00099a002. （原始內容存檔於2019-12-02）.
^ Fulcrand, Hélène; Cheminat, Annie; Brouillard, Raymond; Cheynier, Véronique. Characterization of compounds obtained by chemical oxidation of caffeic acid in acidic conditions. Phytochemistry. 1994, 35 (2): 499–505. doi:10.1016/S0031-9422(00)94790-3.
^ Xu, Peng; Uyama, Hiroshi; Whitten, James E.; Kobayashi, Shiro; Kaplan, David L. Peroxidase-Catalyzed in Situ Polymerization of Surface Orientated Caffeic Acid. J. Am. Chem. Soc. 2005, 127 (33): 11745–11753 [2017-02-05]. doi:10.1021/ja051637r. （原始內容存檔於2019-11-30）.
^ Beavis, R. C.; Chait, B. T. Cinnamic acid derivatives as matrices for ultraviolet laser desorption mass spectrometry of proteins. Rapid Commun. Mass Spectrom. Dec 1989, 3 (12): 432–435 [2017-02-05]. PMID 2520223. doi:10.1002/rcm.1290031207. （原始內容存檔於2017-08-27）.

[1] Gould, Kevin S.; Markham, Kenneth R.; Smith, Richard H.; Goris, Jessica J. Functional role of anthocyanins in the leaves of Quintinia serrata A. Cunn.. Journal of Experimental Botany. 2000, 51 (347): 1107–1115 [2017-02-05]. PMID 10948238. doi:10.1093/jexbot/51.347.1107. （原始內容存檔於2009-06-03）.

[Boerjan-2] 2.0 ^2.1 Boerjan, Wout; Ralph, John; Baucher, Marie. Ligninbiosynthesis. Annual Review of Plant Biology. 2003, 54: 519–546 [2017-02-05]. PMID 14503002. doi:10.1146/annurev.arplant.54.031902.134938. （原始內容存檔於2021-12-04）.

[3] Santos, Sónia A. O.; Freire, Carmen S. R.; Domingues, M. Rosário M.; Silvestre, Armando J. D.; Pascoal Neto, Carlos Pascoal. Characterization of Phenolic Components in Polar Extracts of Eucalyptus globulus Labill. Bark by High-Performance Liquid Chromatography–Mass Spectrometry. Journal of Agricultural and Food Chemistry. 2011, 59 (17): 9386–93. PMID 21761864. doi:10.1021/jf201801q.

[4] Choudhary, M. Iqbal; Naheed, Nadra; Abbaskhan, Ahmed; Musharraf, Syed Ghulam; Siddiqui, Hina; Atta-Ur-Rahman. Phenolic and other constituents of fresh water fern Salvinia molesta. Phytochemistry. 2008, 69 (4): 1018–23. PMID 18177906. doi:10.1016/j.phytochem.2007.10.028.

[pmid18827365-5] Lee, Y.-S.; Kang, Y.-H.; Jung, J.-Y.; Lee, Sanghyun; Ohuchi, Kazuo; Shin, Kuk Hyun; Kang, Il-Jun; Park, Jung Han Yoon; Shin, Hyun-Kyung; Soon, Sung. Protein glycation inhibitors from the fruiting body of Phellinus linteus. Biological & Pharmaceutical Bulletin. October 2008, 31 (10): 1968–1972 [2017-02-04]. PMID 18827365. doi:10.1248/bpb.31.1968. （原始內容存檔於2012-12-19）.

[6] ., Z. Charrouf; ., D. Guillaume. Phenols and Polyphenols from Argania spinosa. American Journal of Food Technology. 2007, 2 (7): 679 [2017-02-04]. doi:10.3923/ajft.2007.679.683. （原始內容存檔於2020-10-20）.

[7] Determination of Flavonoids, Phenolic Acids, and Xanthines in Mate Tea (Ilex paraguariensis St.-Hil.). [2017-02-04]. doi:10.1155/2013/658596. （原始內容存檔於2019-08-23）.

[8] Chemical Composition and Antioxidant Activity of Yerba-Mate (Ilex paraguariensis A.St.-Hil., Aquifoliaceae) Extract as Obtained by Spray Drying. Journal of Analytical Methods in Chemistry. [2017-02-04]. doi:10.1021/jf2008343. （原始內容存檔於2019-12-02）.

[9] Quinde-Axtell, Zory; Baik, Byung-Kee. Phenolic Compounds of Barley Grain and Their Implication in Food Product Discoloration. J. Agric. Food Chem. 2006, 54 (26): 9978–9984 [2017-02-04]. PMID 17177530. doi:10.1021/jf060974w. （原始內容存檔於2021-05-06）.

[pmid11208940-10] 10.0 ^10.1 Olthof, M. R.; Hollman, P. C.; Katan, M. B. Chlorogenic acid and caffeic acid are absorbed in humans. J. Nutr. January 2001, 131 (1): 66–71 [2017-02-05]. PMID 11208940. （原始內容存檔於2020-06-26）.

[11] Pierpoint, W. S. o-Quinones formed in plant extracts. Their reactions with amino acids and peptides. Biochem. J. 1969, 112: 609–616. doi:10.1042/bj1120609.

[12] Rajendra Prasad, N.; Karthikeyan, A.; Karthikeyan, S.; Reddy, B. V. Inhibitory effect of caffeic acid on cancer cell proliferation by oxidative mechanism in human HT-1080 fibrosarcoma cell line. Mol Cell Biochem. Mar 2011, 349 (1–2): 11–19. doi:10.1007/s11010-010-0655-7.

[Hirose-13] 13.0 ^13.1 ^13.2 ^13.3 Hirose, M.; Takesada, Y.; Tanaka, H.; Tamano, S.; Kato, T.; Shirai, T. Carcinogenicity of antioxidants BHA, caffeic acid, sesamol, 4-methoxyphenol and catechol at low doses, either alone or in combination, and modulation of their effects in a rat medium-term multi-organ carcinogenesis model (PDF). Carcinogenesis. 1998, 19 (1): 207–212. PMID 9472713. doi:10.1093/carcin/19.1.207.

[14] Agents Classified by the IARC Monographs （頁面存檔備份，存於網際網路檔案館）, International Agency for Research on Cancer

[15] Peppercorn, M. A.; Goldman, P. Caffeic acid metabolism by gnotobiotic rats and their intestinal bacteria. Proceedings of the National Academy of Sciences. 1972, 69 (6): 1413–1415 [2017-02-05]. PMC 426714 . PMID 4504351. doi:10.1073/pnas.69.6.1413. （原始內容存檔於2008-08-08）.

[16] Gonthier, M.-P.; Verny, M.-A.; Besson, C.; Rémésy, C.; Scalbert, A. Chlorogenic acid bioavailability largely depends on its metabolism by the gut microflora in rats. Journal of Nutrition. 1 June 2003, 133 (6): 1853–1859 [2017-02-05]. PMID 12771329. （原始內容存檔於2009-04-08）.

[17] Cilliers, Johannes J. L.; Singleton, Vernon L. Caffeic acid autoxidation and the effects of thiols. J. Agric. Food Chem. 1990, 38 (9): 1789–1796 [2017-02-05]. doi:10.1021/jf00099a002. （原始內容存檔於2019-12-02）.

[18] Fulcrand, Hélène; Cheminat, Annie; Brouillard, Raymond; Cheynier, Véronique. Characterization of compounds obtained by chemical oxidation of caffeic acid in acidic conditions. Phytochemistry. 1994, 35 (2): 499–505. doi:10.1016/S0031-9422(00)94790-3.

[19] Xu, Peng; Uyama, Hiroshi; Whitten, James E.; Kobayashi, Shiro; Kaplan, David L. Peroxidase-Catalyzed in Situ Polymerization of Surface Orientated Caffeic Acid. J. Am. Chem. Soc. 2005, 127 (33): 11745–11753 [2017-02-05]. doi:10.1021/ja051637r. （原始內容存檔於2019-11-30）.

[pmid2520223-20] Beavis, R. C.; Chait, B. T. Cinnamic acid derivatives as matrices for ultraviolet laser desorption mass spectrometry of proteins. Rapid Commun. Mass Spectrom. Dec 1989, 3 (12): 432–435 [2017-02-05]. PMID 2520223. doi:10.1002/rcm.1290031207. （原始內容存檔於2017-08-27）.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]

[14]

[15]

[16]

[17]

[18]

[19]

[20]