巯基化阿霉素的两种合成方法的比较

吴珊; 张叶叶; 郭海霞; 刘俊杰; 孙治国; 钟延强; 邹豪

doi:10.3969/j.issn.1006-0111.2014.06.008

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巯基化阿霉素的两种合成方法的比较

吴珊, 张叶叶, 郭海霞, 刘俊杰, 孙治国, 钟延强, 邹豪

文章导航 > 药学实践与服务 > 2014 > 32(6): 428-433

吴珊, 张叶叶, 郭海霞, 刘俊杰, 孙治国, 钟延强, 邹豪. 巯基化阿霉素的两种合成方法的比较[J]. 药学实践与服务, 2014, 32(6): 428-433. doi: 10.3969/j.issn.1006-0111.2014.06.008

引用本文:

WU Shan, ZHANG Yeye, GUO Haixia, LIU Junjie, SUN Zhiguo, ZHONG Yanqiang, ZOU Hao. A comparison study of synthesizing methods of thiolated doxorubicin[J]. Journal of Pharmaceutical Practice and Service, 2014, 32(6): 428-433. doi: 10.3969/j.issn.1006-0111.2014.06.008

Citation:

WU Shan, ZHANG Yeye, GUO Haixia, LIU Junjie, SUN Zhiguo, ZHONG Yanqiang, ZOU Hao. A comparison study of synthesizing methods of thiolated doxorubicin[J]. Journal of Pharmaceutical Practice and Service, 2014, 32(6): 428-433. doi: 10.3969/j.issn.1006-0111.2014.06.008

巯基化阿霉素的两种合成方法的比较

doi: 10.3969/j.issn.1006-0111.2014.06.008

1.
第二军医大学药学院药剂学教研室, 上海 200433
2.
解放军266医院, 河北承德 067000

基金项目: 国家自然科学基金项目(30801441);科技部重大新药创制专项(2014ZX09J14107-01B).

A comparison study of synthesizing methods of thiolated doxorubicin

1.
Department of Pharmaceutics, School of Pharmacy, Second Military Medical University, Shanghai 200433, China
2.
NO.266 Hospital of PLA, Chengde 067000, China

摘要: 目的探索合成供金纳米粒载药系统研究用模型药物巯基化阿霉素的可行方法。方法分别采用2-亚氨基硫烷盐酸盐(2-IT)法和琥珀酰亚胺-S-乙酰基硫代乙酸酯(SATA)法合成巯基阿霉素,通过高效液相色谱(HPLC)、飞行时间质谱(MS-ESI)及核磁共振氢谱(¹H NMR)验证巯基阿霉素的合成,并考察反应物摩尔比、反应时间等因素对合成巯基阿霉素的影响。结果 ¹H NMR 确证DOX-SATA出现了与硫酯基团相连的质子信号,表明新合成的化合物中含有硫酯基团。HPLC及MS-ESI结果显示,两种方法均能合成巯基阿霉素,2-IT法生成的巯基阿霉素,随着反应时间延长易发生环化,形成环化巯基阿霉素。SATA试剂法合成巯基阿霉素过程中不易发生副反应,合成的巯基阿霉素较为稳定。结论通过两种方法的比较,SATA法合成巯基阿霉素的方法较为可行。
- 巯基化阿霉素 /
- 2-亚氨基硫烷盐酸盐(2-IT) /
- 琥珀酰亚胺-S-乙酰基硫代乙酸酯(SATA)
Abstract: Objective To investigate the optimal method for synthesizing thiolated doxorubicin. Methods Thiolated doxorubicin was synthesized through two different methods. Doxorubicin was reacted with 2-iminothiolane (2-IT) and S-acetylthioglycolic acid N-hydroxysuccinimide ester (SATA),respectively. The synthesized thiolated doxorubicin was further characterized by HPLC and MS-ESI techniques. Several factors including molar ratios as well as reaction time were evaluated. Results The results showed that thiolated doxorubicin could be synthesized via both of the two methods successfully. Thiolated doxorubicin could be stable when doxorubicin was reacted with SATA. But the crude thiolated doxorubicin could be cyclized easily when doxorubicin was reacted with 2-IT. Conclusion Thiolated doxorubicin prepared with SATA is more feasible than that with 2-IT.
- thiolated doxorubicin /
- 2-iminothiolane (2-IT) /
- S-acetylthioglycolic acid N-hydroxysuccinimide ester (SATA)

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巯基化阿霉素的两种合成方法的比较

doi: 10.3969/j.issn.1006-0111.2014.06.008

1. 第二军医大学药学院药剂学教研室, 上海 200433

2. 解放军266医院, 河北承德 067000

基金项目: 国家自然科学基金项目(30801441);科技部重大新药创制专项(2014ZX09J14107-01B).

收稿日期: 2014-08-02
修回日期: 2014-10-13

关键词:

巯基化阿霉素 /

2-亚氨基硫烷盐酸盐(2-IT) /

琥珀酰亚胺-S-乙酰基硫代乙酸酯(SATA)

摘要: 目的探索合成供金纳米粒载药系统研究用模型药物巯基化阿霉素的可行方法。方法分别采用2-亚氨基硫烷盐酸盐(2-IT)法和琥珀酰亚胺-S-乙酰基硫代乙酸酯(SATA)法合成巯基阿霉素,通过高效液相色谱(HPLC)、飞行时间质谱(MS-ESI)及核磁共振氢谱(¹H NMR)验证巯基阿霉素的合成,并考察反应物摩尔比、反应时间等因素对合成巯基阿霉素的影响。结果 ¹H NMR 确证DOX-SATA出现了与硫酯基团相连的质子信号,表明新合成的化合物中含有硫酯基团。HPLC及MS-ESI结果显示,两种方法均能合成巯基阿霉素,2-IT法生成的巯基阿霉素,随着反应时间延长易发生环化,形成环化巯基阿霉素。SATA试剂法合成巯基阿霉素过程中不易发生副反应,合成的巯基阿霉素较为稳定。结论通过两种方法的比较,SATA法合成巯基阿霉素的方法较为可行。