Total Synthesis and Determination of the Absolute Configuration of Rakicidin A

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• 作者：Feng Sang ; Dongmei Li ; Xiaolong Sun ; Xianqiang Cao ; Liang Wang ; Jianlei Sun ; Bingxia Sun ; Lingling Wu ; Guang Yang ; Xiaoqian Chu ; Jinghan Wang ; Changming Dong ; Yan Geng ; Hong Jiang ; Haibo Long ; Sijia Chen ; Guiyan Wang ; Shuzhong Zhang ; Quan Zhang ; Yue Chen
• 刊名：Journal of the American Chemical Society
• 出版年：2014
• 出版时间：November 5, 2014
• 年：2014
• 卷：136
• 期：44
• 页码：15787-15791
• 全文大小：435K
• ISSN：1520-5126

文摘

Rakicidin A is a cyclic depsipeptide that has exhibited unique growth inhibitory activity against chronic myelogenous leukemia stem cells. Furthermore, rakicidin A has five chiral centers with unknown stereochemical assignment, and thus, can be represented by one of 32 possible stereoisomers. To predict the most probable stereochemistry of rakicidin A, calculations and structural comparison with natural cyclic depsipeptides were applied. A total synthesis of the proposed structure was subsequently completed and highlighted by the creation of a sterically hindered ester bond (C1鈥揅15) through trans-acylation from an easily established isomer (C1鈥揅13). The analytic data of the synthetic target were consistent with that of natural rakicidin A, and then the absolute configuration of rakicidin A was assigned as 2S, 3S, 14S, 15S, 16R. This work suggests strategies for the determination of unknown chiral centers in other cyclic depsipeptides, such as rakicidin B, C, D, BE-43547, and vinylamycin, and facilitates the investigations of rakicidin A as an anticancer stem cell agent.