Protecting-Group-Free One-Step Palladium-Catalyzed Coupling on C25 of Cucurbitacin B Expands Chemical Diversity with Improved Cytotoxicity against A549 Cells  

作　　者：Ning Zhuo Jie Ma Lei Cao Linhai Chen Fajun Nan 

机构地区：[1]University of Chinese Academy of Sciences,No.19A Yuquan Road,Bejing 100049,China [2]State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China [3]School of Chinese Materia Medica,Nanjing University of Chinese Medicine,Nanjing,Jiangsu 210046,China [4]Drug Discovery Shandong Laboratory,Bohai Rim Advanced Research Institute for Drug Discovery,Yantai,Shandong 264117,China

出　　处：《Chinese Journal of Chemistry》2022年第14期1662-1666,I0002,共6页中国化学（英文版）

摘　　要：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.

关 键 词：Natural products Cucurbitacin B Palladium-catalyzed coupling Divergent synthesis Structure-activity relationships 

分 类 号：O62[理学—有机化学]