The Discovery of Potent Antitumor Agent C11-Deoxypsymberin/irciniastatin A: Total Synthesis and Biology of Advanced Psymberin Analogs
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- 作者：Xianhai Huang*† ; ; Ning Shao† ; ; Robert Huryk‡ ; ; Anandan Palani† ; ; Robert Aslanian† ; ; Cynthia Seidel-Dugan*‡ ;
- 刊名：Organic Letters
- 出版年：2009
- 出版时间：February 19, 2009
- 年：2009
- 卷：11
- 期：4
- 页码：867-870
- 全文大小：170K
- 年卷期：v.11,no.4(February 19, 2009)
- ISSN：1523-7052
文摘
Structure−activity relationship (SAR) studies by modification of the unsaturated side chain of potent anticancer marine natural product psymberin/irciniastatin A (1) suggest that substitution at C4 and C5 is important for the cytotoxicity of psymberin, but the terminal double bond is not essential for activity. An aryl group is a good replacement for the olefin. The total synthesis of structurally simplified C11-deoxypsymberin (29) was completed, and its activity is consistently more potent than the natural product which provides a unique opportunity for further SAR studies in the psymberin and pederin family. Preliminary mechanism studies suggest the mode of action of psymberin is through cell apoptosis.