抗肿瘤药Pomalidomide的合成

Synthesis of Antitumor Agent Pomalidomide

N-(叔丁氧羰基)-L-谷氨酰胺(2)经闭环、脱保护制得3-氨基-2,6-哌啶二酮三氟乙酸盐(4)。另用3-硝基邻苯二甲酸(5)脱水制得3-硝基邻苯二甲酸酐(6)。4和6经缩合、铁粉/浓盐酸还原制得免疫调节剂类抗肿瘤药3-氨基-N-(2,6-二氧代-3-哌啶基)-邻苯二甲酰亚胺,以5计总收率约35%。

Pomalidomide, an immunomodulator, was synthesized from 3-nitrophthalic acid （5） by dehydration to give 3-nitrophthalic anhydride （6）, which was subjected to the reaction with 3-aminopiperidine-2,6-dione trifluoroacetate （4） to afford 3-nitro-N-（2,6-dioxopiperidin-3-yl）-phthalimide （7） followed by reduction with Fe/HCl in an overall yield of about 35 % （ based on compound 5）. Compound 4 was prepared from N-Boc-L-glutamine by cyclization and deprotection.