Affiliation:
1. School of Chinese Materia Medica Nanjing University of Chinese Medicine 138 Xianlin Avenue Nanjing 210023 P. R. China
2. State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences 555 Zu Chong Zhi Road Shanghai 201203 P. R. China
3. School of Pharmaceutical Science and Technology Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences Hangzhou 310024 P. R. China
Abstract
AbstractA divergent synthesis of podophyllotoxin derivatives from simple and readily available starting materials through a late‐stage functionalization strategy by rhodium catalysis is reported here. This strategy uses the ketone and oxime in substrates as directing groups. Four kinds of novel podophyllotoxin derivatives have been obtained without any erosion of the enantiopurity, thus indicating the broad substrate scope of this method. Additionally, by using the newly developed strategy, 9 aa, which exhibited excellent anticancer activity, can be prepared by a sequential transformation. In particularly, 9 aa suppressed HeLa cells with IC50 values of 74.5 nM, thus providing a promising lead compound for future drug discovery.
Funder
National Natural Science Foundation of China
Youth Innovation Promotion Association of the Chinese Academy of Sciences
Subject
General Chemistry,Catalysis,Organic Chemistry