title: Total synthesis and determination of the absolute configuration of rakicidin A.
abstract: 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.
authors.affiliation: College of Pharmacy, State Key Laboratory of Elemento-Organic Chemistry, State Key Laboratory of Medicinal Chemical Biology, Nankai University , Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071 P. R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Sang
authors.forename: Dongmei
authors.initials: D
authors.lastname: Li
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Sun
authors.forename: Xianqiang
authors.initials: X
authors.lastname: Cao
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Jianlei
authors.initials: J
authors.lastname: Sun
authors.forename: Bingxia
authors.initials: B
authors.lastname: Sun
authors.forename: Lingling
authors.initials: L
authors.lastname: Wu
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Chu
authors.forename: Jinghan
authors.initials: J
authors.lastname: Wang
authors.forename: Changming
authors.initials: C
authors.lastname: Dong
authors.forename: Yan
authors.initials: Y
authors.lastname: Geng
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.forename: Haibo
authors.initials: H
authors.lastname: Long
authors.forename: Sijia
authors.initials: S
authors.lastname: Chen
authors.forename: Guiyan
authors.initials: G
authors.lastname: Wang
authors.forename: Shuzhong
authors.initials: S
authors.lastname: Zhang
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
mesh_terms: D055666:Lipopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry*; D047630:Depsipeptides
chemical_list: D055666:Lipopeptides; D010456:Peptides, Cyclic; C000723972:rakicidins; D047630:Depsipeptides