化学合成；生命科学。
化学合成；生命科学；医药中间体；生化试剂
合成路线 1（1. 合成：7517-19-3）
产率：100%
合成条件：Stage #1: for 1 h; Cooling with ice Stage #2: at 20 - 66℃; for 6.50 h;
实验步骤：在冰浴下，向100ml圆底烧瓶中加入60ml甲醇，然后通过恒压滴液漏斗（顶部带有干燥管）缓慢加入4ml SOCl2，并用NaOH溶液吸收废气。 搅拌1小时后，加入8mmol L-亮氨酸并在室温下搅拌30分钟，然后在66℃下回流6小时。 通过TLC跟踪反应直至原料消失，用2％茚三酮在乙醇中的溶液作为显色剂。 蒸除溶剂，得到L-亮氨酸甲酯盐酸盐。 产量：100％。
参考文献：
- [1] Patent: US2014/206741, 2014, A1. Location in patent: Paragraph 0121 [2] Journal of Organic Chemistry, 2003, vol. 68, # 12, p. 5006 - 5008 [3] Synthetic Communications, 2010, vol. 40, # 8, p. 1161 - 1179 [4] Bulletin des Societes Chimiques Belges, 1991, vol. 100, # 1, p. 63 - 77 [5] Chemical Biology and Drug Design, 2012, vol. 79, # 2, p. 216 - 222 [6] Journal of the American Chemical Society, 2017, vol. 139, # 40, p. 14077 - 14089 [7] Organic Preparations and Procedures International, 2001, vol. 33, # 4, p. 341 - 349 [8] Organic Preparations and Procedures International, 2002, vol. 34, # 1, p. 87 - 94 [9] Chemistry - A European Journal, 2013, vol. 19, # 49, p. 16615 - 16624 [10] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2006, vol. 45, # 8, p. 1942 - 1944 [11] Synthetic Communications, 2008, vol. 38, # 5, p. 684 - 696 [12] Patent: CN105061236, 2016, B. Location in patent: Paragraph 0034; 0039-0041 [13] Journal of Organic Chemistry, 1989, vol. 54, # 4, p. 937 - 947 [14] European Journal of Medicinal Chemistry, 2016, vol. 112, p. 196 - 208 [15] Journal of the Chemical Society, Perkin Transactions 2, 2001, # 9, p. 1863 - 1868 [16] Patent: US6353006, 2002, B1. Location in patent: Page column 30 [17] Journal of Organometallic Chemistry, 1986, vol. 317, p. 93 - 104 [18] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2007, vol. 46, # 7, p. 1137 - 1142 [19] Synthetic Communications, 2008, vol. 38, # 23, p. 4107 - 4115 [20] Journal of Organic Chemistry, 2012, vol. 77, # 1, p. 317 - 331 [21] Biomedicine and Pharmacotherapy, 2017, vol. 88, p. 1163 - 1172 [22] Journal of Chemical Research, 2009, # 11, p. 665 - 667 [23] Tetrahedron Letters, 2014, vol. 55, # 32, p. 4445 - 4447 [24] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 20, p. 5000 - 5006 [25] New Journal of Chemistry, 2017, vol. 41, # 23, p. 14723 - 14729 [26] Tetrahedron, 1990, vol. 46, # 15, p. 5325 - 5332 [27] Tetrahedron Letters, 1980, vol. 21, p. 2077 - 2080 [28] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 6, p. 1629 - 1632 [29] Heterocycles, 1991, vol. 32, # 10, p. 1879 - 1895 [30] European Journal of Medicinal Chemistry, 1985, vol. 20, # 6, p. 509 - 512 [31] Phytochemistry (Elsevier), 1988, vol. 27, # 1, p. 77 - 84 [32] Journal of Physical Chemistry, 1994, vol. 98, # 27, p. 6862 - 6864 [33] Journal of Organometallic Chemistry, 1987, vol. 326, p. 289 - 298 [34] Journal of Organic Chemistry, 1997, vol. 62, # 20, p. 6862 - 6869 [35] Synthetic Communications, 1999, vol. 29, # 17, p. 3039 - 3049 [36] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1999, vol. 38, # 4, p. 505 - 507 [37] Tetrahedron Asymmetry, 2002, vol. 13, # 18, p. 2053 - 2059 [38] Canadian Journal of Chemistry, 2005, vol. 83, # 8, p. 1164 - 1170 [39] Journal of Medicinal Chemistry, 2006, vol. 49, # 24, p. 7215 - 7226 [40] Tetrahedron, 2007, vol. 63, # 31, p. 7334 - 7348 [41] Journal of Organic Chemistry, 2007, vol. 72, # 24, p. 9283 - 9290 [42] Chemical Communications, 2006, # 29, p. 3081 - 3083 [43] Acta Poloniae Pharmaceutica - Drug Research, 2007, vol. 64, # 6, p. 509 - 516 [44] Tetrahedron Asymmetry, 2009, vol. 20, # 5, p. 616 - 620 [45] Chemistry - A European Journal, 2008, vol. 14, # 35, p. 10888 - 10891 [46] European Journal of Organic Chemistry, 2008, # 14, p. 2423 - 2429 [47] Synlett, 2009, # 8, p. 1227 - 1232 [48] European Journal of Medicinal Chemistry, 2009, vol. 44, # 7, p. 2796 - 2806 [49] Zeitschrift fur Anorganische und Allgemeine Chemie, 2010, vol. 636, # 1, p. 236 - 241 [50] Journal of Chemical Research, 2011, vol. 35, # 1, p. 47 - 50 [51] Synthetic Communications, 2011, vol. 41, # 23, p. 3485 - 3490 [52] Letters in Organic Chemistry, 2011, vol. 8, # 5, p. 358 - 360 [53] Chemistry - An Asian Journal, 2011, vol. 6, # 1, p. 189 - 197 [54] Archiv der Pharmazie, 2011, vol. 344, # 8, p. 494 - 504 [55] Letters in Organic Chemistry, 2011, vol. 8, # 3, p. 210 - 215 [56] Asian Journal of Chemistry, 2012, vol. 24, # 3, p. 1227 - 1236 [57] Journal of Enzyme Inhibition and Medicinal Chemistry, 2012, vol. 27, # 2, p. 302 - 310 [58] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 12, p. 3807 - 3815 [59] Journal of Chemical Research, 2012, vol. 36, # 4, p. 206 - 209 [60] Biomacromolecules, 2012, vol. 13, # 8, p. 2446 - 2455 [61] Medicinal Chemistry Research, 2012, vol. 21, # 11, p. 3361 - 3368 [62] Organic and Biomolecular Chemistry, 2013, vol. 11, # 7, p. 1143 - 1148 [63] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 7, p. 1621 - 1627 [64] European Journal of Medicinal Chemistry, 2016, vol. 108, p. 21 - 27 [65] Journal of Enzyme Inhibition and Medicinal Chemistry, 2013, vol. 28, # 4, p. 717 - 726 [66] Journal of Heterocyclic Chemistry, 2013, vol. 50, # 5, p. 1067 - 1070 [67] RSC Advances, 2013, vol. 3, # 40, p. 18332 - 18338 [68] RSC Advances, 2014, vol. 4, # 24, p. 12275 - 12286 [69] Applied Organometallic Chemistry, 2014, vol. 28, # 7, p. 545 - 551 [70] Organic and Biomolecular Chemistry, 2014, vol. 12, # 41, p. 8318 - 8324 [71] Journal of Medicinal Chemistry, 2015, vol. 58, # 7, p. 3144 - 3155 [72] Oriental Journal of Chemistry, 2015, vol. 31, # 1, p. 417 - 421 [73] Medicinal Chemistry Research, 2015, vol. 24, # 7, p. 2825 - 2837 [74] Journal of Polymer Science, Part A: Polymer Chemistry, 2016, vol. 54, # 8, p. 1065 - 1077 [75] Tetrahedron, 2016, vol. 72, # 51, p. 8486 - 8492 [76] Patent: CN103864642, 2016, B. Location in patent: Paragraph 0019-0021 [77] Organic Syntheses, 1988, vol. 66, p. 151 - 151
合成路线 2（2. 合成：7517-19-3）
产率：98%
合成条件：With thionyl chloride In methanol
实验步骤：（1）与实施例20类似，从6.56g（50.0mmol）D，L-亮氨酸，50ml甲醇和13.0ml（180mmol）亚硫酰氯开始，8.93g（产率：98％）D，L- 得到亮氨酸甲酯盐酸盐，为白色粉末。 1H-NMR（300MHz，D2O）; δ：4.17（1H，t，J = 6.8Hz），3.87（3H，s），1.90（1H，m），1.78（2H，m），00（3H，d，J = 6.0Hz），0.99（3H） ，d，J = 6.0Hz）。
参考文献：
- [1] Patent: US6420415, 2002, B1 [2] Patent: US2012/135921, 2012, A1 [3] Tetrahedron, 2007, vol. 63, # 41, p. 10282 - 10289
