| Doripenem关键中间体的合成工艺研究 |
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| 引用本文： | 王建伟,黄娟,吴勇,王光明.Doripenem关键中间体的合成工艺研究[J].中国抗生素杂志,2006,31(12):746-748. |
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| 作者姓名： | 王建伟 黄娟 吴勇 王光明 |
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| 作者单位： | 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 |
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| 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-琉基毗咯烷，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、硼氧化钠还原、构型反转、Mitsunobu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。
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| 关 键 词： | (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 |
| 文章编号： | 1001-8689(2006)12-0746-03 |
| 收稿时间： | 2006-07-15 |
| 修稿时间： | 2006年7月15日 |
Synthesis of the key intermediate of doripenem |
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| Wang Jian-wei,Huang Juan,Wu Yong,Wang Guang-ming.Synthesis of the key intermediate of doripenem[J].Chinese Journal of Antibiotics,2006,31(12):746-748. |
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| Authors: | Wang Jian-wei Huang Juan Wu Yong Wang Guang-ming |
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| Abstract: | Objective To synthesize(2S,4S)-1-tert-butoxycarbonyl-2-(N-tert-butoxycarbonyl-N-sulfamoyl) aminomethyl-4-mercaptopyrrolidine,the intermediate of doripenem and explore a simple synthetic route for its further development.Method(2S,4S)-1-tert-Butoxycarbonyl-2-(N-tert-butoxycarbonyl-N-sulfamoyl) aminomethyl-4-mercaptopyrrolidine was synthesized from trans-4-hydroxy-L-proline via amine protection,mixed anhydride formation,O-mesylation,NaBH4 reduction,configuration-inversion,Mitsunobu reaction and deacetylation.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. |
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| Keywords: | Doripenem |
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