抗肿瘤药硼替佐米的合成  

Synthesis of Antitumor Drug Bortezomib

作　　者：郑亚东 和龙 贾志丹 王淑娟[1,2] 李铁军 康威 张华[1,3] 

机构地区：[1]国药一心制药有限公司,吉林长春130000 [2]长春工业大学,吉林长春130012 [3]黑龙江大学化学化工与材料学院,黑龙江哈尔滨150080

出　　处：《山东化工》2015年第24期1-3,共3页Shandong Chemical Industry

基　　金：吉林省医药产业发展专项资金计划项目基金(项目号:20130727044YY)

摘　　要：通过(1a R,3a S,4S,6S,7a R-六氢-3a,8,8-三甲基-α-(2-甲基丙基)-4,6-甲桥-1,3,2-苯并二氧硼烷-2-甲胺-2,2,2-三氟乙酸盐与2(S)-N-Boc-氨基-3-苯基丙酸(3)反应得到氨基酸缩合物(4),通过在酸性条件下脱BOC基团得到脱保护物(5),再与吡嗪-2-羧酸(6)缩合,异丁基硼酸脱去蒎烷基团得到高选择性蛋白酶体抑制剂抗肿瘤药物硼替佐米(1),反应总收率约为40.0%。目标产物经核磁共振氢谱、碳谱、质谱及红外光谱结构确证。该合成工艺条件温和、操作简便、收率高、纯度好、易于工业化生产。High selective proteasome inhibitor antitumor drug bortezomib is synthesized in four steps. The synthetic route is as follows： firstly,compound（ 4） is obtained through condensation reaction between（ 1a R,3a S,4S,6S,7a R）- hexahydro- 3a,8,8- trimethyl- alpha-（ 2- methylpropyl）- 4,6- methano- 1,3,2- benzodioxaborole- 2- methanamine- 2,2,2- trifluoroacetate（ 2） and 2（ S）- N- BOC- amino- 3- phenylpropionic acid（ 3）,Compound（ 4） was removed BOC group under acid condition to obtain deprotection compound（ 5）. Secondly,compound（ 7） is synthesized through condensation reaction between compound（ 5） and pyrazine- 2- carboxylic acid（ 6）. Finally,compound（ 7） was removed pinane group by isobutaneboronic acid to give bortezomib（ 1）. The structure of bortezomib was confirmed by1 HNMR,13CNMR,MS and IR. The synthetic method has the advantages of cheap raw materials,few reaction steps,mild reaction conditions and higher product purity,which is favorable for industrial application.

关 键 词：硼替佐米 合成 抗肿瘤药 

分 类 号：TQ463[化学工程—制药化工]