Synthesis of Paclitaxel Side Chain via Multi-Component Reaction and Its Application to the Synthesis of Paclitaxel Analogues

doi:10.6023/cjoc201806031

Chin. J. Org. Chem. ›› 2019, Vol. 39 ›› Issue (2): 377-389.DOI: 10.6023/cjoc201806031 Previous Articles Next Articles

ARTICLE

多组分反应合成紫杉醇侧链及其在合成紫杉醇衍生物中的应用

盛家骏^a, 于雅楠^a, 王信^a,b, 钱宇^b, 符立梧^c, 赵芸^a, 马明亮^a, 胡文浩^a,b

a 华东师范大学上海分子治疗与新药创制工程技术研究中心上海 200062;
b 中山大学药学院广州 510006;
c 中山大学肿瘤防治中心广州 510060

收稿日期:2018-07-24 修回日期:2018-12-17 发布日期:2018-12-21
通讯作者: 马明亮, 胡文浩 E-mail:mlma@brain.ecnu.edu.cn;huwh9@mail.sysu.edu.cn
基金资助:
国家自然科学基金（Nos.21572067，21332003）资助项目.

Synthesis of Paclitaxel Side Chain via Multi-Component Reaction and Its Application to the Synthesis of Paclitaxel Analogues

Sheng Jiajun^a, Yu Ya'nan^a, Wang Xin^a,b, Qian Yu^b, Fu Liwu^c, Zhao Yun^a, Ma Mingliang^a, Hu Wenhao^a,b

a Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, Shanghai 200062;
b School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006;
c Cancer Center, Sun Yat-sen University, Guangzhou 510060

Received:2018-07-24 Revised:2018-12-17 Published:2018-12-21
Contact: 10.6023/cjoc201806031 E-mail:mlma@brain.ecnu.edu.cn;huwh9@mail.sysu.edu.cn
Supported by:
Project supported by the National Natural Science Foundation of China (Nos. 21572067, 21332003).

1. Synthesis of Paclitaxel Side Chain via Multi-Component Reaction and Its Application to the Synthesis of Paclitaxel Analogues.PDF(3272KB)

Abstract

Under the catalysis of Cu(OTf)₂, a hydroxy ylide trapping based multi-component reaction using water, diazoacetates, aromatic aldehydes and aromatic amines was successfully carried out to construct α-hydroxy-β-amino acid ester skeleton in one step. The taxol oxazolidine-type side chains were efficiently synthesized after further chemical transformations. Moreover, 14 taxane derivatives were synthesized through esterification of obtained side chains and 7-O-(triethylsilyl) baccatin Ⅲ or 7,10-dimethoxy-10-beacetyl baccatin Ⅲ, and several novel compounds with excellent activity were discovered in the test of anti-tumor activity. In this paper, combining the methodology and application of multi-component reaction, a highly efficient method for synthesizing paclitaxel side chain derivatives was developed, which was applied into the semi-synthesis of paclitaxel analogues. This research provided a new approach to the study of structure-activity relationship and had potential application value.

Key words: taxol side chain, paclitaxel analogues, multi-component reaction, hydroxy ylide

Cite this article

Sheng Jiajun, Yu Ya'nan, Wang Xin, Qian Yu, Fu Liwu, Zhao Yun, Ma Mingliang, Hu Wenhao. Synthesis of Paclitaxel Side Chain via Multi-Component Reaction and Its Application to the Synthesis of Paclitaxel Analogues[J]. Chin. J. Org. Chem., 2019, 39(2): 377-389.

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多组分反应合成紫杉醇侧链及其在合成紫杉醇衍生物中的应用

Synthesis of Paclitaxel Side Chain via Multi-Component Reaction and Its Application to the Synthesis of Paclitaxel Analogues

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