化学合成；生命科学。
医药; 有机合成
合成路线 1（1. 合成：3190-71-4）
产率：89.2%
合成条件：With phosgene In tetrahydrofuran at 45 - 65℃; for 1.08 h;
实验步骤：实施例2：制备L-谷氨酸N-羧酸酐，γ-苄基酯;在该实施例中，将3.3升无水四氢呋喃和466g（1.96摩尔）L-谷氨酸γ-苄基酯的搅拌混合物用0.5升/分钟的液体表面氮气吹扫并加热至45℃。超过30分钟。将氮气吹扫增加至2升/分钟，并以一定速率加入389g（3.93摩尔）气态光气，以在10分钟内保持反应混合物温度为50°-65℃。使用干冰/丙酮回流冷凝器将光气回流到反应容器中。加入光气后，将反应混合物在50°-65℃加热25分钟直至固体消失，得到澄清溶液。从回流冷凝器中取出干冰和丙酮，用氮气以4升/分钟和50℃-65℃吹扫反应混合物30分钟。通过在50°-65℃下真空汽提至15mmHg除去四氢呋喃和过量的光气，随后浓缩的残余物结晶。 EPO将汽提的残余物溶于2.8升无水乙酸乙酯中，真空过滤混浊的混合物以除去不溶的固体。在搅拌下将无水己烷（5.5升）逐渐加入到滤液中以使产物结晶。将产物浆液搅拌30分钟并在5℃下冷藏过夜。通过在氮气层下真空过滤分离产物，用0.93升3：1的己烷，乙酸乙酯和1.4升己烷的溶液洗涤，在漏斗中通过抽真空干燥30分钟，同时保持正氮气在室温下吹扫并真空干燥至恒重。干燥后，制备461g（产率89.2％）L-谷氨酸N-羧酸酐，γ-苄基酯，熔点为92°-94℃，氯化物含量为0.022％。
参考文献：
- [1] Patent: WO2006/47703, 2006, A2. Location in patent: Page/Page column 12-13 [2] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1982, p. 1317 - 1324 [3] Journal of the Chemical Society, 1950, p. 3239,3243 [4] Biomacromolecules, 2011, vol. 12, # 10, p. 3797 - 3804
合成路线 2（2. 合成：3190-71-4）
产率：95%
合成条件：at 70℃; Inert atmosphere
实验步骤：该合成类似于N-ε-苄氧基羰基-L-赖氨酸-N-羧酸酐的合成。 10.01g（42.1mmol）苄基酯保护的谷氨酰胺和200mL abs。 使用THF并加入4.07mL（33.7mmol）双光气。 获得10.52g纯化产物（40mmol;产率95％;无色针状物;熔点：93-94℃（点燃：93-94℃[38]））并在-80℃下储存在Schlenk管中。。 1H NMR（300MHz，CDCl3）：δ[ppm] = 9.11（1H，s，-NH-），7.42-7.20（5H，m，C6H5），5.10（2H，s，-CH2-C6H5），4.47（ 1H，dd（3JH，H = 7.9,5.5Hz）， - CO-CH-NH-），2.50（2H，t（3JH，H = 7.9Hz），BnO-CO-CH2-），2.15-1.85（2H） ，m，-CH2-CH-）。
参考文献：
- [1] Biomacromolecules, 2014, vol. 15, # 2, p. 548 - 557 [2] Macromolecular Bioscience, 2015, vol. 15, # 1, p. 63 - 73 [3] Polymer, 2015, vol. 67, p. 240 - 248 [4] Synthetic Communications, 2017, vol. 47, # 1, p. 53 - 61 [5] Journal of Organic Chemistry, 1985, vol. 50, # 5, p. 715 - 716 [6] Patent: US2015/87788, 2015, A1. Location in patent: Paragraph 0059; 0065; 0066; 0067; 0068; [7] Bulletin of the Chemical Society of Japan, 1994, vol. 67, # 3, p. 742 - 747
合成路线 3（3. 合成：3190-71-4）
产率：89%
合成条件：at 55℃; for 1.50 h; Inert atmosphere
实验步骤：在氩气下向250mL火焰干燥的圆底烧瓶中加入BGlu（6.2g，26mmol）和三光气（3.7g，13mmol）。 然后，加入无水THF（130mL）并将反应混合物在55℃下搅拌90分钟。 然后将澄清的反应混合物真空浓缩，然后在己烷中沉淀。 产物从THF /己烷中结晶三次。 产量：6.1克（89％）。
参考文献：
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