Facile Synthesis of 7-epi-Taxane and Its Derivatives and Preliminary Evaluation of Anticancer Activity  

作　　者：Zhao Li Jia Feng Kun Zou Zhuo Yang Yong Zhang Zhijian Xu Bo Li Jiye Shi Yiming Li Weiliang Zhu Kaixian Chen 

机构地区：[1]School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China [2]CAS Key Laboratory of Receptor Research, Drug Discovery and Design Centre, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China [3]Nano Science and Technology Institute, University of Science and Technology of China, Suzhou, Jiangsu 215123, China [4]UCB Biopharma SPRL, Chemin du Foriest, Braine-l'Alleud, Belgium [5]Kellogg College, University of Oxford, 60-62 Banbury Road, Oxford, OX2 6PN, United Kingdom

出　　处：《Chinese Journal of Chemistry》2016年第11期1165-1176,共12页中国化学（英文版）

摘　　要：7-epi-Taxane has been achieved efficiently in gram scale from natural taxane via inversion of the 7-hydroxyl group simply using Ag20 as catalyst and DMF as solvent. The catalyst could he quantitatively recovered by filtra- tion without loss of catalytic activity. This condition is also applicable to the direct epimerization of taxane derivatives （e.g., docetaxel and paclitaxel） to 7-epi-taxane derivatives （e.g., 7-epi-docetaxel and 7-epi-paclitaxel）. Furthermore, 33 ester derivatives of 7-epi-taxane with different amino acid moieties at the position of C-13 were successfully synthesized via esterification without protecting C-7-OH. Bioassay results revealed that compounds 13 and 18 have good selectivity against prostatic cancer cell line DU145, with ICs0 value as low as 15.9 nmol/L for 18.7-epi-Taxane has been achieved efficiently in gram scale from natural taxane via inversion of the 7-hydroxyl group simply using Ag20 as catalyst and DMF as solvent. The catalyst could he quantitatively recovered by filtra- tion without loss of catalytic activity. This condition is also applicable to the direct epimerization of taxane derivatives （e.g., docetaxel and paclitaxel） to 7-epi-taxane derivatives （e.g., 7-epi-docetaxel and 7-epi-paclitaxel）. Furthermore, 33 ester derivatives of 7-epi-taxane with different amino acid moieties at the position of C-13 were successfully synthesized via esterification without protecting C-7-OH. Bioassay results revealed that compounds 13 and 18 have good selectivity against prostatic cancer cell line DU145, with ICs0 value as low as 15.9 nmol/L for 18.

关 键 词：TAXANE 7-epi-taxane silver oxide amino acid C-13 derivative of taxane anticancer activity 

分 类 号：O643.36[理学—物理化学] O636.1[理学—化学]