Citation: 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]. Chinese Journal of Organic Chemistry, ;2019, 39(2): 377-389. doi: 10.6023/cjoc201806031 shu

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

Corresponding author: Ma Mingliang, mlma@brain.ecnu.edu.cn Hu Wenhao, huwh9@mail.sysu.edu.cn
Received Date: 24 July 2018
Revised Date: 17 December 2018
Available Online: 21 February 2018
Fund Project: the National Natural Science Foundation of China 21332003the National Natural Science Foundation of China 21572067Project supported by the National Natural Science Foundation of China (Nos. 21572067, 21332003)

Figures(4)

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.
- taxol side chain,
- paclitaxel analogues,
- multi-component reaction,
- hydroxy ylide
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