摘要
目的制备用于新型多肽类药物全合成研究的非必需氨基酸N-叔丁氧羰基-DL-(±)-高酪氨酸(1)。方法以L-天冬氨酸(2)为原料,经N-甲氧羰基保护、分子内脱水酸酐化、与邻氯苯甲醚的Friedel-Crafts反应、10%钯碳催化氢化、48%氢溴酸脱N-甲氧羰基和酚甲醚保护、N-叔丁氧羰基保护6步反应合成了目标化合物。结果以总收率49.7%成功地合成了目标化合物1,其结构经电喷雾质谱(ESI-MS)、氢谱(1H NMR)和碳谱(13C NMR)确认。结论该合成路线具有原料价廉易得、操作简便、总收率高等优点。
Objective To prepare N-tert-butoxycarbonyl-DL-（± ）-homo-tyrosine （1） , a key unusual amino acid and pharmaceutical intermediate for the total synthesis of novel peptides drug including cyclic or straight chain peptide. Methods Starting from L-aspartic acid （2） , the target compound 1 was synthesized via 6 steps including N-methoxycarbouylation, intramolecular dehy- dration and anhydridation, Friedel-Crafts reaction with 2-chloroanisole, catalytic hydrogenation with 10% Pd-C, N-demethoxycarbony- lation and demethylation with 48% HBr-HOAc followed by N-Butoxyearbonylation. Results Target compound 1 had been successfully synthesized in an overall yield of 49.7%. The structure of the target compound was confirmed by ESI-MS, 1H NMR and 13C NMR. Conclusion The process developed has several advantages such as cheap materials, convenient workup and high yield.
出处
《药学实践杂志》
CAS
2010年第5期345-347,384,共4页
Journal of Pharmaceutical Practice
基金
国家自然科学基金(30772674
30930107)
上海市重点学科建设基金(B906)资助项目
