N-alkoxycarbonyl-glutamic and aspartic acids. Studies on the activation and cyclodehydration and side-reaction encountered in analysis of glutamic acid using Fmoc-chloride.

F M Chen, N L Benoiton
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Abstract

N-Alkoxycarbonylaminodicarboxylic acids were reacted in dichloromethane with N-ethyl-N'-(dimethylaminopropyl)carbodiimide hydrochloride, and with methyl chloroformate in the presence of N-methylmorpholine. Removal of secondary products by washing the mixtures with aqueous solutions gave good yields of the pure crystalline internal anhydrides. Anhydrides of N-benzyloxycarbonyl- (Z) and N-9-fluorenylmethoxycarbonyl-(Fmoc) L-glutamic and L-aspartic acids and of N-tert.-butoxycarbonyl-L-aspartic acid were prepared in this way. The compounds were shown to be amenable to normal phase high-performance liquid chromatography (NP-HPLC) on a CN-column using tert.-butanol-hexane as solvent. The products of the reactions of Z- and Fmoc-glutamic acid with hot acetic anhydride were examined by nuclear magnetic resonance and NP-HPLC before and after methanolysis in an attempt to establish if any of the corresponding pyroglutamates were formed. The reaction of Fmoc-chloride with Fmoc-glutamate was examined for the same reason. It is concluded that the side product generated during the reaction of Fmoc-chloride with glutamic acid which is used for analysis of the latter is the N-protected internal anhydride and not the pyroglutamate as reported in the literature.

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n -烷氧羰基谷氨酸和天冬氨酸。fmoc -氯化物分析谷氨酸时的活化、环脱水及副反应研究。
n -烷氧羰基氨基二羧酸在二氯甲烷中与n -乙基- n '-(二甲氨基丙基)卡二亚胺盐酸盐以及在n -甲基吗啡啉存在下与氯甲酸甲酯反应。用水溶液洗涤混合物,除去二次产物,得到了纯度较高的结晶内酸酐。n -苄基氧羰基-(Z)和n -9-氟酰甲氧羰基-(Fmoc) l-谷氨酸和l-天冬氨酸和n -叔丁基的酸酐。用此方法制备了-丁氧羰基- l-天冬氨酸。结果表明,这些化合物可以用正相高效液相色谱法(NP-HPLC)在n -色谱柱上使用。-丁醇-己烷为溶剂。用核磁共振和NP-HPLC检测了Z-和fmoc -谷氨酸与热乙酸酐反应前后的产物,试图确定是否有相应的焦谷氨酸生成。基于同样的原因,研究了氯化物与谷氨酸盐的反应。结果表明,用于分析谷氨酸的Fmoc-chloride与谷氨酸反应产生的副产物是n保护的内酸酐,而不是文献中报道的焦谷氨酸。
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