化学合成。
医药
合成路线 1（1. 合成：4339-72-4）
产率：99%
合成条件：at 20℃; Schlenk technique
实验步骤：在25mL干燥的Schelenk烧瓶中，将乙酸（2.50当量）加入到10mL无水吡啶中的齐墩果酸（2,0mmol，1.00当量）中。将反应混合物缓慢升温至室温（rt）过夜。反应 将混合物用水洗涤数次并用乙酸乙酯萃取。然后用MgSO 4干燥。将滤液真空浓缩，得到纯的对羟基苯甲酸，用于下一步骤（> 99％）。
参考文献：
- [1] European Journal of Medicinal Chemistry, 2009, vol. 44, # 10, p. 4112 - 4120 [2] Bioorganic and Medicinal Chemistry Letters, 1999, vol. 9, # 14, p. 1889 - 1894 [3] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 6, p. 1629 - 1632 [4] Carbohydrate Research, 2009, vol. 344, # 5, p. 599 - 605 [5] Chemical Communications, 2018, vol. 54, # 35, p. 4473 - 4476 [6] Patent: CN108129348, 2018, A. Location in patent: Paragraph 0106; 0107; 0108 [7] Life Sciences, 2006, vol. 79, # 14, p. 1349 - 1356 [8] Journal of Molecular Structure, 2017, vol. 1136, p. 173 - 181 [9] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 17, p. 4114 - 4119 [10] Journal of Chemical Research, Miniprint, 2000, # 2, p. 326 - 339 [11] Chinese Chemical Letters, 2012, vol. 23, # 4, p. 403 - 406 [12] European Journal of Medicinal Chemistry, 2014, vol. 72, p. 84 - 101 [13] European Journal of Medicinal Chemistry, 2016, vol. 118, p. 64 - 78 [14] Journal of Medicinal Chemistry, 2016, vol. 59, # 6, p. 2396 - 2409 [15] European Journal of Medicinal Chemistry, 2014, vol. 74, p. 278 - 301 [16] Bioorganic Chemistry, 2016, vol. 68, p. 137 - 151 [17] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2004, vol. 43, # 10, p. 2175 - 2177 [18] Patent: CN103864880, 2016, B. Location in patent: Paragraph 0262; 0263 [19] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 1, p. 594 - 615 [20] Patent: CN106749486, 2017, A. Location in patent: Paragraph 0030; 0034 [21] Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 24, p. 3115 - 3118 [22] Organic and Biomolecular Chemistry, 2013, vol. 11, # 10, p. 1726 - 1738 [23] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 3, p. 907 - 909 [24] European Journal of Medicinal Chemistry, 2017, vol. 127, p. 1 - 9 [25] European Journal of Medicinal Chemistry, 2018, vol. 159, p. 143 - 148 [26] Molecules, 2008, vol. 13, # 7, p. 1472 - 1486 [27] Archives of Pharmacal Research, 2017, vol. 40, # 4, p. 458 - 468 [28] European Journal of Medicinal Chemistry, 2018, vol. 155, p. 869 - 879 [29] Scientific Papers of the Institute of Physical and Chemical Research (Japan), 1932, vol. 18, p. 83,95 [30] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1931, vol. 199, p. 56,62 [31] Journal of the Chemical Society, 1939, p. 1045,1047 [32] Yakugaku Zasshi, 1947, vol. 67, p. 206 [33] Chem.Abstr., 1951, p. 9069 [34] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1931, vol. 195, p. 132 [35] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1931, vol. 198, p. 182 [36] Yakugaku Zasshi, 1930, vol. 50, p. 1076,1086; dtsch. Ref. S. 139 [37] Chem. Zentralbl., 1931, vol. 102, # I, p. 1118 [38] Scientific Papers of the Institute of Physical and Chemical Research (Japan), 1932, vol. 18, p. 83,95 [39] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1931, vol. 199, p. 56,62 [40] Journal of the Chemical Society, 1939, p. 1045,1047 [41] Yakugaku Zasshi, 1947, vol. 67, p. 206 [42] Chem.Abstr., 1951, p. 9069 [43] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1931, vol. 195, p. 132 [44] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1931, vol. 198, p. 182 [45] Yakugaku Zasshi, 1930, vol. 50, p. 1076,1086; dtsch. Ref. S. 139 [46] Chem. Zentralbl., 1931, vol. 102, # I, p. 1118 [47] Yakugaku Zasshi, 1933, vol. 53, p. 680,685; dtsch. Ref. S. 129 [48] Chem.Abstr., 1934, p. 1998 [49] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1931, vol. 199, p. 64,66, 71 [50] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1932, vol. 211, p. 5,16 [51] Yakugaku Zasshi, 1933, vol. 53, p. 680,685; dtsch. Ref. S. 129 [52] Chem.Abstr., 1934, p. 1998 [53] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1931, vol. 199, p. 56,62 [54] Journal of the Chemical Society, 1939, p. 1045,1047 [55] Helvetica Chimica Acta, 1936, vol. 19, p. 1136 [56] Helvetica Chimica Acta, 1937, vol. 20, p. 229 Anm. 3 [57] Yakugaku Zasshi, 1930, vol. 50, p. 1076,1086; dtsch. Ref. S. 139 [58] Chem. Zentralbl., 1931, vol. 102, # I, p. 1118 [59] Scientific Papers of the Institute of Physical and Chemical Research (Japan), 1932, vol. 18, p. 83,95 [60] Yakugaku Zasshi, 1933, vol. 53, p. 680,685; dtsch. Ref. S. 129 [61] Chem.Abstr., 1934, p. 1998 [62] Yakugaku Zasshi, 1947, vol. 67, p. 206 [63] Chem.Abstr., 1951, p. 9069 [64] Yakugaku Zasshi, 1933, vol. 53, p. 680,685; dtsch. Ref. S. 129 [65] Chem.Abstr., 1934, p. 1998 [66] Journal of Biological Chemistry, 1938, vol. 123, p. 641,651, 652 [67] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1931, vol. 199, p. 64,66, 71 [68] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1932, vol. 211, p. 5,16 [69] Yakugaku Zasshi, 1933, vol. 53, p. 680,685; dtsch. Ref. S. 129 [70] Chem.Abstr., 1934, p. 1998 [71] Helvetica Chimica Acta, 1936, vol. 19, p. 1136 [72] Helvetica Chimica Acta, 1937, vol. 20, p. 229 Anm. 3 [73] Journal of Biological Chemistry, 1938, vol. 123, p. 641,651, 652 [74] Yakugaku Zasshi, 1933, vol. 53, p. 680,685; dtsch. Ref. S. 129 [75] Chem.Abstr., 1934, p. 1998 [76] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1931, vol. 195, p. 132 [77] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1931, vol. 198, p. 182 [78] Phytochemistry (Elsevier), 1990, vol. 29, # 11, p. 3601 - 3604 [79] Pharmazie, 1980, vol. 35, # 8, p. 500 - 501 [80] Planta Medica, 1993, vol. 59, # 4, p. 369 - 372 [81] Journal of the Indian Chemical Society, 1987, vol. 64, p. 774 - 775 [82] Journal of Pharmacy and Pharmacology, 2002, vol. 54, # 4, p. 583 - 588 [83] Chemical and Pharmaceutical Bulletin, 1992, vol. 40, # 2, p. 401 - 405 [84] Phytochemistry (Elsevier), 1982, vol. 21, # 7, p. 1832 - 1833 [85] Journal of Natural Products, 2002, vol. 65, # 12, p. 1939 - 1941 [86] Journal of Natural Products, 2006, vol. 69, # 11, p. 1531 - 1538 [87] Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 18, p. 8697 - 8705 [88] Archiv der Pharmazie, 2009, vol. 342, # 10, p. 569 - 576 [89] Tetrahedron, 2011, vol. 67, # 23, p. 4206 - 4211 [90] Chemical and Pharmaceutical Bulletin, 2011, vol. 59, # 8, p. 1051 - 1056 [91] European Journal of Medicinal Chemistry, 2014, vol. 87, p. 316 - 327 [92] Chemistry and Biodiversity, 2014, vol. 11, # 9, p. 1354 - 1363 [93] Research on Chemical Intermediates, 2015, vol. 41, # 9, p. 6257 - 6269 [94] PLoS ONE, 2015, vol. 10, # 5, [95] Bioorganic Chemistry, 2016, vol. 68, p. 152 - 158 [96] Journal of Natural Products, 2018,
合成路线 2（2. 合成：4339-72-4）
产率：48%
合成条件：Stage #1: With triethylamine In dichloromethane at 0℃; for 0.50 h; Stage #2: at 30℃; Microwave irradiation
实验步骤：一般程序：在0℃下充分搅拌并冷却，在无水CH 2 Cl 2中滴加OA（1.0当量）溶液，滴加2.1当量。 Et3N。 将混合物反应在0℃下搅拌30分钟。 在5分钟内逐滴加入酰氯（1.1当量），然后将混合物反应在微波辐射下置于30℃的设备CEM中。在真空下浓缩溶剂，并通过FCC纯化粗反应。
参考文献：
- [1] European Journal of Medicinal Chemistry, 2014, vol. 87, p. 316 - 327 [2] Yakugaku Zasshi, 1933, vol. 53, p. 680,685; dtsch. Ref. S. 129 [3] Chem.Abstr., 1934, p. 1998 [4] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1931, vol. 199, p. 56,62 [5] Scientific Papers of the Institute of Physical and Chemical Research (Japan), 1932, vol. 18, p. 83,95 [6] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1931, vol. 199, p. 56,62 [7] Yakugaku Zasshi, 1947, vol. 67, p. 206 [8] Chem.Abstr., 1951, p. 9069 [9] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1931, vol. 199, p. 56,62 [10] Journal of Biological Chemistry, 1938, vol. 123, p. 641,651, 652 [11] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1931, vol. 199, p. 56,62 [12] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1931, vol. 195, p. 132 [13] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1931, vol. 198, p. 182 [14] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1931, vol. 199, p. 64,66, 71 [15] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1932, vol. 211, p. 5,16 [16] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1931, vol. 199, p. 56,62 [17] Journal of the Chemical Society, 1939, p. 1045,1047 [18] Helvetica Chimica Acta, 1936, vol. 19, p. 1136 [19] Helvetica Chimica Acta, 1937, vol. 20, p. 229 Anm. 3 [20] Yakugaku Zasshi, 1930, vol. 50, p. 1076,1086; dtsch. Ref. S. 139 [21] Chem. Zentralbl., 1931, vol. 102, # I, p. 1118
合成路线 3（3. 合成：4339-72-4）
产率：73%
合成条件：Stage #1: for 2 h; Reflux Stage #2: Heating
实验步骤：通用方法：将三萜酸（10g，22mmol，1.0当量）的乙酸酐（160mL）溶液在回流下搅拌2小时。 向热反应混合物中缓慢加入乙酸（20mL）和水（40mL）。 滤出沉淀物，用水（4×50mL），冷EtOH（20mL）洗涤并减压干燥。得到产物，为白色固体。
参考文献：
- [1] European Journal of Medicinal Chemistry, 2018, vol. 152, p. 21 - 30 [2] Scientific Papers of the Institute of Physical and Chemical Research (Japan), 1932, vol. 18, p. 83,95 [3] Yakugaku Zasshi, 1934, vol. 54, p. 1077,1079; dtsch. Ref. S. 233 [4] Chem. Zentralbl., 1935, vol. 106, # I, p. 3293 [5] Acta Phytochimica, 1936, vol. 9, p. 43,61, 75 [6] Chem. Zentralbl., 1936, vol. 107, # II, p. 3541,3543 [7] Yakugaku Zasshi, 1930, vol. 50, p. 1076,1086; dtsch. Ref. S. 139 [8] Chem. Zentralbl., 1931, vol. 102, # I, p. 1118
