Total Synthesis and Determination of the Absolute Configuration of Rakicidin A

被引：38

作者：

Sang, Feng ^{[1
]}

Li, Dongmei ^{[1
]}

Sun, Xiaolong ^{[1
,2
]}

Cao, Xianqiang ^{[1
,2
]}

Wang, Liang ^{[1
]}

Sun, Jianlei ^{[1
,2
]}

Sun, Bingxia ^{[1
,2
]}

Wu, Lingling ^{[1
,2
]}

Yang, Guang ^{[1
]}

Chu, Xiaoqian ^{[2
]}

Wang, Jinghan ^{[1
,2
]}

Dong, Changming ^{[1
]}

Geng, Yan ^{[1
,2
]}

Jiang, Hong ^{[3
]}

Long, Haibo ^{[4
]}

Chen, Sijia ^{[4
]}

Wang, Guiyan ^{[5
]}

Zhang, Shuzhong ^{[1
]}

Zhang, Quan ^{[1
]}

Chen, Yue ^{[1
]}

机构：

[1] Nankai Univ, Collaborat Innovat Ctr Chem Sci & Engn Tianjin, State Key Lab Med Chem Biol, Coll Pharm,State Key Lab Elementoorgan Chem, Tianjin 300071, Peoples R China

[2] Tianjin Int Joint Acad Biomed, Tianjin 300457, Peoples R China

[3] Fujian Inst Microbiol, Fujian Prov Key Lab Screening Novel Microbial Pro, Fuzhou 350007, Peoples R China

[4] Southern Med Univ, Nanfang Hosp, Div Nephrol, Guangzhou 510515, Guangdong, Peoples R China

[5] Accendatech, Tianjin 300384, Peoples R China

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2014年 / 136卷 / 44期

基金：

中国国家自然科学基金;

关键词：

CANCER STEM-CELLS; REVISION; ANALOGS; STEVASTELINS; DEPSIPEPTIDE; PEPTIDES; LEUKEMIA;

D O I：

10.1021/ja509379j

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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-C15) through trans-acylation from an easily established isomer (C1-C13). 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.

引用

页码：15787 / 15791

页数：5

共 42 条

[1] Total synthesis of motuporin (nodularin-V) [J].