19685-10-0Relevant articles and documents
A new strategy to improve the metabolic stability of lactone: Discovery of (20 S,21 S)-21-fluorocamptothecins as novel, hydrolytically stable topoisomerase i inhibitors
Miao, Zhenyuan,Zhu, Lingjian,Dong, Guoqiang,Zhuang, Chunlin,Wu, Yuelin,Wang, Shengzheng,Guo, Zizao,Liu, Yang,Wu, Shanchao,Zhu, Shiping,Fang, Kun,Yao, Jianzhong,Li, Jian,Sheng, Chunquan,Zhang, Wannian
, p. 7902 - 7910 (2013)
Lactone is a common structural motif in biologically active natural products. However, the metabolic instability of lactone significantly reduces their in vivo potency. In the present investigation, a new strategy to improve the metabolic stability of lactone was provided by the design of α-fluoro ether as a novel bioisostere of lactone. The effectiveness of the α-fluoro ether/lactone replacement was validated by the discovery of (20S,21S)-21-fluorocamptothecins as hydrolytically stable topoisomerase I inhibitors. A highly potent camptothecin derivative, 8l, was successfully identified, which showed excellent in vitro and in vivo antitumor activities and represents a promising lead for the discovery of novel antitumor agents. Interestingly, this study also provided a new structure-activity relationship for the C21-carbonyl group of camptothecin, which has been regarded as an essential pharmacophore. Our results revealed that the conserved C21-carbonyl group can be replaced by a fluorine substituent. α-Fluoro ether may have general application in improving the metabolic stability of lactone.
CONJUGATES OF A CELL-BINDING MOLECULE WITH CAMPTOTHECIN ANALOGS
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Page/Page column 144, (2021/10/30)
Provided are conjugates of camptothecin analogs with a cell-binding molecule of formula (I), wherein R1, R2, R3, R4, R5, X, L, n, m, T and ----- are defined herein. It also provides methods of making the conjugates of camptothecin analogs to a cell-binding agent, as well as methods of using the conjugates in targeted treatment of cancer, infection, and immunological disorders.
Visible-Light-Induced Radical Cascade Cyclization: Synthesis of (20S)-Camptothecin, SN-38 and Irinotecan
Yuan, Yao,Dong, Wuheng,Gao, Xiaoshuang,Xie, Xiaomin,Curran, Dennis P.,Zhang, Zhaoguo
, p. 1035 - 1040 (2018/09/25)
(20S)-Camptothecin, irinotecan and SN-38 were successfully synthesized by a photocatalyzed radical cascade cyclization from an N-propargyl iodopyridinone and an arylisonitrile under visible light with a ruthenium catalyst. This synthetic method provided a useful entry into composing camptothecin family of antitumor agents in good yields under mild reaction conditions without the use of heavy metal reagents.
Short protecting group-free syntheses of camptothecin and 10-hydroxycamptothecin using cascade methodologies
Xu, Peng,Chen, Dong-Sheng,Xi, Jie,Yao, Zhu-Jun
, p. 976 - 981 (2015/04/14)
A convergent protecting group-free total synthesis route of camptothecin and 10-hydroxycamptothecin has been developed in this work. Cascade oxidation of 3-(hydroxymethyl)furan-2(5 H)-one and in situ intermolecular oxa Diels-Alder reaction with vinyl ether was developed and applied to construct the E-ring, and TMSCl-promoted cascade closure of the D-ring delivered the whole skeleton of the alkaloids in the total synthesis. The new short syntheses were advantageous with regard to step economy, low cost, easily available starting materials and reagents, and convenient operations.
