13748-90-8 L-α-羟基异己酸

运输信息：常温运输。危险描述：非危险化学品，WGK Germany:3，TSCA listed，海关编码:29181990，存储类别:11 - 可燃固体

L-alpha-羟基异己酸是一种基于隐藻霉素的大环二肽的合成试剂，用作微管蛋白抑制剂；Leucic acid ((S)-α-hydroxyisocaproic acid)是支链氨基酸leucine的代谢物，leucine在合成肌肉蛋白中发挥重要作用；靶点为Human Endogenous Metabolite

化学合成；生命科学

合成路线 1（1. 合成：13748-90-8）

产率：73% 合成条件：at 0 - 20℃; for 17 h; 实验步骤：搅拌并冷却至0℃，1-亮氨酸或1-异亮氨酸（24.92g，0.189mol）在1.25M H₂SO₄（125mL）中的溶液，亚硝酸钠溶液（19.73g，0.286mol）逐滴加入（在）H₂O（100mL）中。然后将混合物在0℃下搅拌2小时，然后在室温下搅拌15小时。此后，用乙醚（6×75mL）萃取烧瓶内容物。将有机层用MgSO₄干燥，蒸发乙醚，得到适当的粗α-羟基羧酸2c或2d，将其用己烷-乙醚混合物重结晶纯化。 参考文献：[1] Organic Letters, 2012, vol.14, #16, p.4246-4249；[2] Organic Letters, 2006, vol.8, #14, p.2993-2996；[3] European Journal of Organic Chemistry, 2009, #31, p.5390-5405；[4] ACS Chemical Neuroscience, 2013, vol.4, #8, p.1204-1216；[5] Journal of the Chemical Society, Perkin Transactions 1, 1993, #1, p.11-14；[6] Organic and Biomolecular Chemistry, 2010, vol.8, #21, p.4940-4948；[7] Tetrahedron Asymmetry, 2011, vol.22, #3, p.294-299；[8] Chemical and Pharmaceutical Bulletin, 1994, vol.42, #11, p.2394-2396；[9] Journal of Organic Chemistry, 2009, vol.74, #19, p.7220-7229；[10] Tetrahedron Letters, 1999, vol.40, #19, p.3811-3814；[11] Journal of Organic Chemistry, 1995, vol.60, #19, p.6082-6084；[12] Journal of Organic Chemistry, 2017, vol.82, #9, p.4949-4957；[13] European Journal of Medicinal Chemistry, 2015, vol.93, p.55-63；[14] Angewandte Chemie (International Edition), 1997, vol.36, #1-2, p.122-125；[15] Bioorganic and Medicinal Chemistry Letters, 1999, vol.9, #4, p.563-568；[16] Bioorganic and Medicinal Chemistry Letters, 2014, vol.24, #1, p.165-167；[17] Liebigs Annales, 1996, #12, p.1963-1964；[18] Tetrahedron, 2004, vol.60, #41, p.9163-9170；[19] Biochemische Zeitschrift, 1921, vol.122, p.256；[20] Patent: US2461701, 1945；[21] Journal of the American Chemical Society, 1956, vol.78, p.2423,2428；[22] Journal of the American Chemical Society, 1956, vol.73, p.1336；[23] Tetrahedron, 1976, vol.32, #10, p.1101-1106；[24] Roczniki Chemii, 1971, vol.45, p.677-679；[25] Journal of the American Chemical Society, 1971, vol.93, #16, p.4084-4085；[26] Bulletin de la Societe Chimique de France, 1972, p.4217-4224；[27] Tetrahedron Letters, 1975, p.2187-2190；[28] Tetrahedron Letters, 1989, vol.30, #38, p.5109-5110；[29] Journal of Organic Chemistry, 1993, vol.58, #7, p.1646-1648；[30] Tetrahedron Letters, 1995, vol.36, #36, p.6449-6452；[31] Synthesis, 1995, #10, p.1223-1224；[32] Journal of Organic Chemistry, 1997, vol.62, #7, p.2292-2297；[33] Tetrahedron Letters, 1997, vol.38, #40, p.6961-6964；[34] Bioorganic and Medicinal Chemistry Letters, 2002, vol.12, #12, p.1625-1628；[35] Journal of Organic Chemistry, 2000, vol.65, #22, p.7667-7675；[36] Journal of Organic Chemistry, 2001, vol.66, #22, p.7303-7312；[37] Journal of the American Chemical Society, 2007, vol.129, #23, p.7264-7265；[38] Helvetica Chimica Acta, 1963, vol.46, #85, p.766-780；[39] Tetrahedron, 2008, vol.64, #14, p.3197-3203；[40] Patent: US2008/146513, 2008, A1；[41] Angewandte Chemie - International Edition, 2008, vol.47, #29, p.5451-5455；[42] Chemistry - A European Journal, 2014, vol.20, #35, p.11225-11228；[43] Chemistry - A European Journal, 2014, vol.20, #35, p.11225-11228；[44] Chemistry - A European Journal, 2016, vol.22, #49, p.17600-17611；[45] European Journal of Medicinal Chemistry, 2018, vol.156, p.21-42；[46] Patent: US2461701, 1945；[47] Journal of the American Chemical Society, 1956, vol.78, p.2423,2428；[48] Journal of the American Chemical Society, 1956, vol.73, p.1336；[49] Tetrahedron, 1976, vol.32, #10, p.1101-1106；[50] Roczniki Chemii, 1971, vol.45, p.677-679；[51] Journal of the American Chemical Society, 1971, vol.93, #16, p.4084-4085；[52] Bulletin de la Societe Chimique de France, 1972, p.4217-4224；[53] Tetrahedron Letters, 1975, p.2187-2190；[54] Tetrahedron Letters, 1989, vol.30, #38, p.5109-5110；[55] Journal of Organic Chemistry, 1993, vol.58, #7, p.1646-1648；[56] Tetrahedron Letters, 1995, vol.36, #36, p.6449-6452；[57] Synthesis, 1995, #10, p.1223-1224；[58] Journal of Organic Chemistry, 1997, vol.62, #7, p.2292-2297；[59] Tetrahedron Letters, 1997, vol.38, #40, p.6961-6964；[60] Bioorganic and Medicinal Chemistry Letters, 2002, vol.12, #12, p.1625-1628；[61] Journal of Organic Chemistry, 2000, vol.65, #22, p.7667-7675；[62] Journal of Organic Chemistry, 2001, vol.66, #22, p.7303-7312；[63] Journal of the American Chemical Society, 2007, vol.129, #23, p.7264-7265；[64] Helvetica Chimica Acta, 1963, vol.46, #85, p.766-780；[65] Tetrahedron, 2008, vol.64, #14, p.3197-3203；[66] Patent: US2008/146513, 2008, A1；[67] Angewandte Chemie - International Edition, 2008, vol.47, #29, p.5451-5455；[68] Chemistry - A European Journal, 2014, vol.20, #35, p.11225-11228；[69] Chemistry - A European Journal, 2016, vol.22, #49, p.17600-17611；[70] European Journal of Medicinal Chemistry, 2018, vol.156, p.21-42； 一般步骤：将L-亮氨酸（24.92 g，0.189 mol）溶于1.25 M H₂SO₄（125 mL）中，搅拌并冷却至0℃。在搅拌下，逐滴加入亚硝酸钠（19.73 g，0.286 mol）的水溶液（100 mL）。加毕，将反应混合物在0℃下继续搅拌2小时，随后升至室温搅拌15小时。反应完成后，用乙醚（6×75 mL）萃取反应混合物。合并有机层，用无水MgSO₄干燥，过滤后减压浓缩除去乙醚，得到粗产物L-α-羟基异己酸（2c或2d）。粗产物通过己烷-乙醚混合溶剂重结晶纯化。 参考文献：[1] Organic Letters, 2012, vol.14, #16, p.4246-4249；[2] Organic Letters, 2006, vol.8, #14, p.2993-2996；[3] European Journal of Organic Chemistry, 2009, #31, p.5390-5405；[4] ACS Chemical Neuroscience, 2013, vol.4, #8, p.1204-1216；[5] Journal of the Chemical Society, Perkin Transactions 1, 1993, #1, p.11-14；[6] Organic and Biomolecular Chemistry, 2010, vol.8, #21, p.4940-4948；[7] Tetrahedron Asymmetry, 2011, vol.22, #3, p.294-299；[8] Chemical and Pharmaceutical Bulletin, 1994, vol.42, #11, p.2394-2396；[9] Journal of Organic Chemistry, 2009, vol.74, #19, p.7220-7229；[10] Tetrahedron Letters, 1999, vol.40, #19, p.3811-3814；[11] Journal of Organic Chemistry, 1995, vol.60, #19, p.6082-6084；[12] Journal of Organic Chemistry, 2017, vol.82, #9, p.4949-4957；[13] European Journal of Medicinal Chemistry, 2015, vol.93, p.55-63；[14] Angewandte Chemie (International Edition), 1997, vol.36, #1-2, p.122-125；[15] Bioorganic and Medicinal Chemistry Letters, 1999, vol.9, #4, p.563-568；[16] Bioorganic and Medicinal Chemistry Letters, 2014, vol.24, #1, p.165-167；[17] Liebigs Annales, 1996, #12, p.1963-1964；[18] Tetrahedron, 2004, vol.60, #41, p.9163-9170；[19] Biochemische Zeitschrift, 1921, vol.122, p.256；[20] Patent: US2461701, 1945；[21] Journal of the American Chemical Society, 1956, vol.78, p.2423,2428；[22] Journal of the American Chemical Society, 1956, vol.73, p.1336；[23] Tetrahedron, 1976, vol.32, #10, p.1101-1106；[24] Roczniki Chemii, 1971, vol.45, p.677-679；[25] Journal of the American Chemical Society, 1971, vol.93, #16, p.4084-4085；[26] Bulletin de la Societe Chimique de France, 1972, p.4217-4224；[27] Tetrahedron Letters, 1975, p.2187-2190；[28] Tetrahedron Letters, 1989, vol.30, #38, p.5109-5110；[29] Journal of Organic Chemistry, 1993, vol.58, #7, p.1646-1648；[30] Tetrahedron Letters, 1995, vol.36, #36, p.6449-6452；[31] Synthesis, 1995, #10, p.1223-1224；[32] Journal of Organic Chemistry, 1997, vol.62, #7, p.2292-2297；[33] Tetrahedron Letters, 1997, vol.38, #40, p.6961-6964；[34] Bioorganic and Medicinal Chemistry Letters, 2002, vol.12, #12, p.1625-1628；[35] Journal of Organic Chemistry, 2000, vol.65, #22, p.7667-7675；[36] Journal of Organic Chemistry, 2001, vol.66, #22, p.7303-7312；[37] Journal of the American Chemical Society, 2007, vol.129, #23, p.7264-7265；[38] Helvetica Chimica Acta, 1963, vol.46, #85, p.766-780；[39] Tetrahedron, 2008, vol.64, #14, p.3197-3203；[40] Patent: US2008/146513, 2008, A1；[41] Angewandte Chemie - International Edition, 2008, vol.47, #29, p.5451-5455；[42] Chemistry - A European Journal, 2014, vol.20, #35, p.11225-11228；[43] Chemistry - A European Journal, 2014, vol.20, #35, p.11225-11228；[44] Chemistry - A European Journal, 2016, vol.22, #49, p.17600-17611；[45] European Journal of Medicinal Chemistry, 2018, vol.156, p.21-42；[46] Patent: US2461701, 1945；[47] Journal of the American Chemical Society, 1956, vol.78, p.2423,2428；[48] Journal of the American Chemical Society, 1956, vol.73, p.1336；[49] Tetrahedron, 1976, vol.32, #10, p.1101-1106；[50] Roczniki Chemii, 1971, vol.45, p.677-679；[51] Journal of the American Chemical Society, 1971, vol.93, #16, p.4084-4085；[52] Bulletin de la Societe Chimique de France, 1972, p.4217-4224；[53] Tetrahedron Letters, 1975, p.2187-2190；[54] Tetrahedron Letters, 1989, vol.30, #38, p.5109-5110；[55] Journal of Organic Chemistry, 1993, vol.58, #7, p.1646-1648；[56] Tetrahedron Letters, 1995, vol.36, #36, p.6449-6452；[57] Synthesis, 1995, #10, p.1223-1224；[58] Journal of Organic Chemistry, 1997, vol.62, #7, p.2292-2297；[59] Tetrahedron Letters, 1997, vol.38, #40, p.6961-6964；[60] Bioorganic and Medicinal Chemistry Letters, 2002, vol.12, #12, p.1625-1628；[61] Journal of Organic Chemistry, 2000, vol.65, #22, p.7667-7675；[62] Journal of Organic Chemistry, 2001, vol.66, #22, p.7303-7312；[63] Journal of the American Chemical Society, 2007, vol.129, #23, p.7264-7265；[64] Helvetica Chimica Acta, 1963, vol.46, #85, p.766-780；[65] Tetrahedron, 2008, vol.64, #14, p.3197-3203；[66] Patent: US2008/146513, 2008, A1；[67] Angewandte Chemie - International Edition, 2008, vol.47, #29, p.5451-5455；[68] Chemistry - A European Journal, 2014, vol.20, #35, p.11225-11228；[69] Chemistry - A European Journal, 2016, vol.22, #49, p.17600-17611；[70] European Journal of Medicinal Chemistry, 2018, vol.156, p.21-42；