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科技导报 | 研究论文 2010,28(13): 82-86
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科技导报 | 研究论文 2010, 28(13): 82-86
多西他赛合成工艺
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徐少杰,袁建勇,周 辉,甘勇军,李勤耕
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    重庆医科大学药学院,重庆 400016

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李勤耕
Study on Synthesis of Docetaxel
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出版时间: 2010-07-13
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采用新型合成工艺,以求在高收率的基础上制备高纯度的多西他赛。以10-DABIII为起始原料,经氯甲酸苄酯类化合物酯化反应,制得C-7,C-10-苄氧羰基类保护的10-DABIII,然后与(3R,4S)-1-叔丁氧羰基-4-苯基氮杂环丁烷-2-酮反应,形成2'-(1-乙氧基乙基)-N-脱苯甲酰-N-叔丁氧羰基-C-7,C-10-二-苄氧羰基类-10-去乙酰紫杉醇,又经氢解,得到2'-(1-乙氧基乙基)-N-脱苯甲酰-N-叔丁氧羰基-10-去乙酰紫杉醇,最后经稀酸水解得目标物多西他赛。该工艺探讨了各主要因素对反应过程的影响,确立了各步反应的最佳反应条件。所制备的目标化合物和各中间体经质谱和核磁的确证。实验结果表明该合成工艺具有成本低、易操作、收率高等优点。
多西他赛  /  抗癌药  /  合成
For the purpose of preparing docetaxel with a high yield, a mild and convenient semi-synthetic process of docetaxel is adopted. The target compound is prepared in four steps. 10-deacetyl baccatin III, the starting material, is reacted with benzyl chloroformate to form C-7 and C-10-protected 10-deacetyl baccatin III, which is then reacted with (3R,4S)-1-tert-butoxy-carbonyl-3-(1-ethoxy-ethyloxy)-4-phenylaz-etidin-2-one and followed by hydrogenolysis to form a 2'-(1-ethoxy-ethyloxy)-N-off benzoyl-N-tert-butyl carbonyl oxy-gen-10-deacetyl taxol, and then, the target compound is finally obtained by the acid hydrolysis. The key step is the selective protection of C-7 and C-10 hydroxyl groups of 10-deacetyl baccatin III. The effects of main factors on every reaction process are analyzed, to establish the optimized reaction conditions of every step. The target molecules and intermediates are characterized by MS and NMR. The results indicate that the synthetic process is of low cost, easy for handling and with an overall yield of 50% from 10-deacetyl baccatin III.
docetaxel  /  anticancer drugs  /  synthesis
徐少杰;袁建勇;周 辉;甘勇军;李勤耕. 多西他赛合成工艺. 科技导报, 2010 , 28 (13) : 82 -86 .
. Study on Synthesis of Docetaxel[J]. Science & Technology Review, 2010 , 28 (13) : 82 -86 .
2010年第28卷第13期
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  • 接收时间:2010-05-12
  • 首发时间:2010-07-13
  • 出版时间:2010-07-13
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  • 收稿日期:2010-05-12
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2种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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