Protecting-Group-Free One-Step Palladium-Catalyzed Coupling on C25 of Cucurbitacin B Expands Chemical Diversity with Improved Cytotoxicity against A549 Cells
Ning Zhuo
University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049 China
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203 China
Search for more papers by this authorJie Ma
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203 China
Search for more papers by this authorLei Cao
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203 China
School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210046 China
Search for more papers by this authorLinhai Chen
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203 China
Search for more papers by this authorCorresponding Author
Fajun Nan
University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049 China
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203 China
Drug Discovery Shandong Laboratory, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, Shandong, 264117 China
E-mail: [email protected]Search for more papers by this authorNing Zhuo
University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049 China
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203 China
Search for more papers by this authorJie Ma
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203 China
Search for more papers by this authorLei Cao
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203 China
School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210046 China
Search for more papers by this authorLinhai Chen
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203 China
Search for more papers by this authorCorresponding Author
Fajun Nan
University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049 China
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203 China
Drug Discovery Shandong Laboratory, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, Shandong, 264117 China
E-mail: [email protected]Search for more papers by this authorComprehensive Summary
The natural product cucurbitacin B has been widely studied because of its multiple biological activities, especially its potent antitumor effects. However, modifications of cucurbitacin B are mainly focused on the C2 and C16 site, studies on the C25 acetoxy group are still limited. We successfully developed a palladium-catalyzed allylic coupling of cucurbitacin B with boronic acids, providing a one-step approach to expand the chemical diversity of the C25 position. Our method was protecting-group-free, showing a good functional group tolerance and a wide substrate scope under mild reaction conditions. A library of 29 derivatives was prepared, compounds 2q and 2u showed higher cytotoxicity against A549 cells than cucurbitacin B, compounds 2n and 2o maintained potency, and the introduced hydroxyl and amino groups could be further derived.
Supporting Information
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