Doripenem关键中间体的合成工艺研究  

Synthesis of the key intermediate of doripenem

作　　者：王建伟[1] 黄娟[1] 吴勇[1] 王光明 

机构地区：[1]四川大学华西药学院,成都610041 [2]成都英创科技发展有限责任公司,成都610051

出　　处：《中国抗生素杂志》2006年第12期746-748,共3页Chinese Journal of Antibiotics

摘　　要：目的合成doripenem关键中间体(2S,4S)-1-叔丁氧羰基-2-(N-叔丁氧羰基-N-氨磺酰)氨甲基-4-巯基吡咯烷,为进一步研究开发奠定基础。方法以反式-4-羟基-L-脯氨酸为原料,经氨基保护、制成混酐、甲磺酰化、硼氢化钠还原、构型反转、M itsunobu反应、脱乙酰基得到目标化合物。结果目标化合物经红外光谱、核磁共振氢谱和质谱确证其化学结构,总收率达到43.4%。结论本文探索了简便的doripenem侧链的合成工艺,为该工艺用于中试放大提供了依据。Objective To synthesize （2S, 4S）-l-tert-butoxyearbonyl-2-（N-tert-butoxyearbonyl-N- sulfamoyl） aminomethyl-4-mereaptopyrrolidine, the intermediate of doripenem and explore a simple synthetic route for its further development. Method （2S, 4S）-1-tert-Butoxyearbonyl-2-（N-tert-butoxyearbonyl-N- sulfamoyl） aminomethyl-4-mereaptopyrrolidine was synthesized from trans-4-hydroxy-L-proline via amine protection, mixed anhydride formation, O-mesylation, NaBH4 reduction, configuration-inversion, Mitsunobu reaction and deaeetylation. Results The chemical structure of the target compound was confirmed by IR, ^1H-NMR and MS. The title compound was obtained in 43.4% overall yield. Conclusions The proposed method is feasible to synthesize the title compound and is suitable for large-scale preparation.

关 键 词：DORIPENEM (2S 4S)-1-叔丁氧羰基-2-(N-叔丁氧羰基-N-氨磺酰)氨甲基-4-巯基吡咯烷 碳青霉烯 合成 

分 类 号：R978.11[医药卫生—药品]