3068-32-4 2,3,4,6-四-O-乙酰基-α-D-吡喃半乳糖基溴

干冰运输。危险性质：非危险化学品。WGK Germany:3。F:8-10-21。海关编码:29329990。存储类别:11 - 可燃固体。危险性类别:眼部刺激 类别2；经皮刺激 类别2；特异性靶器官毒性-一次接触，类别3。

化学合成；生命科学。2,3,4,6-四乙酰氧基-alpha-D-吡喃糖溴化物具有特殊的化学性质和药用活性，是许多医药、农药的中间体，应用前景非常广阔。其还可用作医药及医药中间体、染发助剂、聚合物稳定剂、感光材料的抗氧化剂和抗灰雾剂等。

医药; 农药; 中间体; 染发助剂; 聚合物稳定剂; 感光材料抗氧化剂和抗灰雾剂

路线1：

• 步骤: 将β-D-半乳糖五乙酸酯（5.00g，12.8mmol）和溴化铋（III）（287mg，640μmol）溶解在二氯甲烷（25mL）中，向该溶液中加入溴代三乙基硅烷（6.76mL，51.2mmol），将混合物在室温下在氩气氛下搅拌3小时。将反应混合物倒入冰冷却的饱和碳酸氢钠水溶液中，然后用二氯甲烷萃取混合物，用盐水洗涤有机层。用硫酸钠干燥有机层，除去溶剂，得到2,3,4,6-四-O-乙酰基-α-D-吡喃半乳糖基溴（5.30g，定量）。
• 条件: With bismuth(III) bromide; triethyl-bromo-silane In dichloromethane at 20℃; for 3 h;
• 产率: 100%
• 参考文献: [1] Synthesis, 2010, #13, p.2201-2206 [2] Bioorganic and Medicinal Chemistry Letters, 2012, vol.22, #4, p.1719-1721 [3] Patent: US9250232, 2016, B2. Location in patent: Page/Page column 23 [4] Green Chemistry, 2017, vol.19, #11, p.2687-2694 [5] Journal of the American Chemical Society, 2013, vol.135, #24, p.9055-9077 [6] Patent: US2012/259102, 2012, A1. Location in patent: Page/Page column 2 [7] Angewandte Chemie - International Edition, 2012, vol.51, #31, p.7812-7816 [8] Journal of Natural Products, 2018, vol.81, #2, p.371-377 [9] Recueil des Travaux Chimiques des Pays-Bas, 1985, vol.104, p.116-119 [10] Patent: US2007/218010, 2007, A1. Location in patent: Page/Page column 15; 20 [11] Phytochemistry, 2014, vol.100, p.126-311 [12] Organic Letters, 2002, vol.4, #11, p.1863-1866 [13] Tetrahedron Letters, 2013, vol.54, #52, p.7124-7126 [14] Chemical and pharmaceutical bulletin, 2003, vol.51, #11, p.1268-1272 [15] Organic Letters, 2005, vol.7, #12, p.2385-2388 [16] Angewandte Chemie - International Edition, 2012, vol.51, #29, p.7137-7141 [17] Bioorganic and Medicinal Chemistry Letters, 2008, vol.18, #24, p.6374-6376 [18] Organic and Biomolecular Chemistry, 2018, vol.16, #40, p.7430-7437 [19] Bioorganic and Medicinal Chemistry Letters, 2018, vol.28, #4, p.594-600 [20] European Journal of Organic Chemistry, 2007, #29, p.4927-4934 [21] European Journal of Medicinal Chemistry, 2008, vol.43, #1, p.210-221 [22] Chemical Communications, 2013, vol.49, #15, p.1494-1496 [23] Patent: WO2017/189553, 2017, A1. Location in patent: Paragraph 0586; 0589; 0590; 0591 [24] Chemische Berichte, 1929, vol.62, p.833,846 [25] Biochemical Preparations, 1955, vol.4, p.1,3 Anm.4 [26] Carbohydrate Research, 1985, vol.139, p.225-236 [27] Journal of Carbohydrate Chemistry, 1994, vol.13, #1, p.129-132 [28] Journal of the American Chemical Society, 1994, vol.116, #25, p.11315-11322 [29] Journal of Organic Chemistry, 1995, vol.60, #13, p.3942-3943 [30] Tetrahedron Letters, 2000, vol.41, #8, p.1137-1140 [31] Carbohydrate Research, 2005, vol.340, #12, p.2052-2054 [32] Angewandte Chemie - International Edition, 2005, vol.44, #7, p.1057-1061 [33] Organic Letters, 2001, vol.3, #17, p.2629-2632 [34] Bioorganic and Medicinal Chemistry Letters, 2007, vol.17, #7, p.1971-1978 [35] Carbohydrate Research, 1996, vol.295, p.41-55 [36] Synthesis, 2008, #21, p.3453-3460 [37] European Journal of Inorganic Chemistry, 2008, #25, p.3943-3947 [38] Chemical Communications, 2010, vol.46, #14, p.2441-2443 [39] Chinese Journal of Chemistry, 2010, vol.28, #4, p.605-612 [40] Organic Letters, 2010, vol.12, #13, p.2974-2977 [41] Bioorganic and Medicinal Chemistry Letters, 2010, vol.20, #20, p.5994-5996 [42] Patent: EP1712555, 2006, A1. Location in patent: Page/Page column 10 [43] Journal of Organic Chemistry, 2010, vol.75, #20, p.6747-6755 [44] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2010, vol.49, #11, p.1499-1508 [45] Synthesis, 2011, #24, p.4003-4010 [46] European Journal of Medicinal Chemistry, 2012, vol.52, p.184-192 [47] Bioorganic and Medicinal Chemistry Letters, 2013, vol.23, #3, p.646-649 [48] Steroids, 2014, vol.80, p.71-79 [49] Journal of Surfactants and Detergents, 2014, vol.17, #2, p.261-268 [50] Phosphorus, Sulfur and Silicon and the Related Elements, 2014, vol.189, #1, p.81-87 [51] Patent: WO2014/190024, 2014, A1. Location in patent: Paragraph 00124 [52] Bioorganic and Medicinal Chemistry Letters, 2014, vol.24, #18, p.4523-4528 [53] Chemistry - A European Journal, 2015, vol.21, #33, p.11779-11787 [54] Carbohydrate Research, 2016, vol.421, p.33-39 [55] Chemical Communications, 2016, vol.52, #11, p.2284-2287 [56] Journal of Organic Chemistry, 2016, vol.81, #14, p.5851-5865 [57] Patent: CN102977160, 2016, B. Location in patent: Paragraph 0028 [58] Synthesis (Germany), 2017, vol.49, #1, p.42-52 [59] Patent: CN106974897, 2017, A. Location in patent: Paragraph 0043-0045 [60] Journal of the American Chemical Society, 2017, vol.139, #35, p.12121-12124 [61] Journal of Medicinal Chemistry, 2018, vol.61, #7, p.2937-2948 [62] Bioorganic Chemistry, 2019, vol.84, p.326-338 [63] Chinese Chemical Letters, 2018

路线2：

• 步骤: 在0℃下，将溴化氢在乙酸（33％，5mL）中的溶液滴加到1,2,3,4,6-五-O-乙酰基 - （α1）-D-吡喃半乳糖（500mg，1.28 mmol）中。在室温下搅拌2小时后，将二氯甲烷（30mL）加入到反应中。用冰冷的水小心地洗涤溶液，并用MgSO4干燥有机层。真空蒸发溶剂，得到1.04g（98％）半乳糖基溴化物3。
• 条件: With hydrogen bromide; tert -butyl alcohol In acetic acid at 0 - 20℃;
• 产率: 98%
• 参考文献: [1] Organic and Biomolecular Chemistry, 2012, vol.10, #30, p.6211-6216 [2] Carbohydrate Research, 1997, vol.297, #2, p.175-180 [3] Farmaco, 2001, vol.56, #4, p.319-324 [4] Journal of Carbohydrate Chemistry, 1999, vol.18, #2, p.225-239 [5] Patent: WO2011/51733, 2011, A2. Location in patent: Page/Page column 72 [6] Medicinal Chemistry Research, 2018, vol.27, #3, p.705-708 [7] European Journal of Organic Chemistry, 2001, #14, p.2697-2705 [8] Angewandte Chemie - International Edition, 2009, vol.48, #42, p.7798-7802 [9] Organic Letters, 2017, vol.19, #21, p.5802-5805 [10] Journal of the American Chemical Society, 2008, vol.130, #10, p.2928-2929 [11] Journal of the American Chemical Society, 2008, vol.130, #51, p.17494-17501 [12] Angewandte Chemie - International Edition, 2017, vol.56, #5, p.1416-1421 [13] Angew. Chem., 2017, vol.129, #5, p.1438-1443,6 [14] Journal of the American Chemical Society, 2018, vol.140, #17, p.5682-5685 [15] Journal of Heterocyclic Chemistry, 2011, vol.48, #5, p.1028-1038 [16] Journal of Organic Chemistry, 2010, vol.75, #11, p.3859-3862 [17] Organic and Biomolecular Chemistry, 2017, vol.15, #26, p.5602-5608 [18] Patent: US2006/34774, 2006, A1. Location in patent: Page/Page column 6 [19] Organic and Biomolecular Chemistry, 2012, vol.10, #15, p.3019-3032 [20] Carbohydrate Research, 1996, vol.288, p.25-44 [21] Steroids, 1998, vol.63, #1, p.44-49 [22] Journal of Carbohydrate Chemistry, 1999, vol.18, #8, p.937-959 [23] Carbohydrate Research, 2005, vol.340, #17, p.2670-2674 [24] Journal of Organic Chemistry, 2005, vol.70, #24, p.9740-9754 [25] Journal of the American Chemical Society, 2002, vol.124, #33, p.9756-9767 [26] Journal of the Chemical Society. Perkin Transactions 1, 2001, #7, p.880-885 [27] Journal of Fluorine Chemistry, 2007, vol.128, #5, p.562-565 [28] European Journal of Medicinal Chemistry, 2008, vol.43, #12, p.2778-2783 [29] Patent: WO2005/70911, 2005, A1. Location in patent: Page/Page column 38-39 [30] Synlett, 2009, #16, p.2609-2612 [31] Synthesis, 2010, #5, p.763-769 [32] Journal of Organometallic Chemistry, 2012, vol.702, p.1-9 [33] E-Journal of Chemistry, 2011, vol.8, #4, p.1614-1619 [34] Journal of the Brazilian Chemical Society, 2012, vol.23, #6, p.1062-1069 [35] Tetrahedron, 2013, vol.69, #14, p.3019-3026 [36] Chemical Communications, 2013, vol.49, #92, p.10808-10810 [37] Medicinal Chemistry Research, 2014, vol.23, #1, p.496-502 [38] Organic and Biomolecular Chemistry, 2014, vol.12, #16, p.2592-2595 [39] Research on Chemical Intermediates, 2015, vol.41, #5, p.2929-2937 [40] Patent: EP2910563, 2015, A1. Location in patent: Paragraph 0099 [41] Synthesis (Germany), 2016, vol.48, #19, p.3339-3351 [42] Journal of Chemistry, 2018, vol.2018, [43] Carbohydrate Research, 2018, vol.458-459, p.67-76 [44] Letters in Organic Chemistry, 2018, vol.15, #10, p.822-825

路线3：

• 步骤: 向100mL三颈烧瓶中加入乙酸酐（30mL）冰水浴滴加3滴70％高氯酸，搅拌10分钟，分批加入D-半乳糖（5.00g），控制反应温度在30-40℃，反应1.5小时后，通过加入红磷（3.75g）将反应溶液冷却至15℃。搅拌10分钟后，缓慢滴加液体溴（2.8mL），温度控制在20°C以下，滴加后，将混合物在15-20°C搅拌0.5小时，继续控制温度在20℃以下，缓慢滴加去离子水（4.5mL）在15-20℃反应约0.5h，室温放置2h，加入CH2Cl2（40mL），过滤，滤液倒入200mL冰水中，分离有机层，水层用CH2Cl2（4×30mL）萃取。有机层，有机相用饱和NaHCO3溶液洗涤至中性，用饱和盐水洗涤，用无水Na2SO4干燥，浓缩，得到总乙酰化单甘油酯，不再与下一步骤直接反应。将上述得到的全乙酰溴 - 半乳糖溶于100mLDMSO中，室温下分批加入NaN3（2.7g），室温反应2h，将反应溶液倒入400mL去离子水中，CH2Cl2萃取（4×50mL），饱和盐水洗涤，无水Na2SO4干燥，过滤，浓缩，纯化硅胶柱（PE / EA = 4：1）。获得白色固体（7.25g，70％）。
• 条件: Stage #1: With perchloric acid In water for 0.17 h; Cooling with ice Stage #2: at 30 - 40℃; for 1.50 h; Stage #3: With phosphorus; bromine In water at 15 - 20℃; for 2.50 h;
• 产率: 70%
• 参考文献: [1] Carbohydrate Research, 2012, vol.361, p.189-194 [2] Tetrahedron Letters, 2010, vol.51, #32, p.4182-4185 [3] Synthetic Communications, 2008, vol.38, #23, p.4116-4124 [4] Patent: CN106554378, 2017, A. Location in patent: Paragraph 0037; 0038 [5] Carbohydrate Research, 2005, vol.340, #17, p.2670-2674 [6] Journal of Carbohydrate Chemistry, 2006, vol.25, #7, p.595-614 [7] European Journal of Medicinal Chemistry, 2010, vol.45, #3, p.1001-1007 [8] Organic and Biomolecular Chemistry, 2010, vol.8, #3, p.632-639 [9] Tetrahedron, 2014, vol.70, #39, p.7032-7043