ChemMedChem p. 891 - 897 (2021)
Update date:2022-08-04
Topics:
Zumbrunn, Cornelia
Krüsi, Daniela
Stamm, Christina
Caspers, Patrick
Ritz, Daniel
Rueedi, Georg
Ribosomal protein synthesis is an important target in antibacterial drug discovery. Numerous natural products have served as starting points for the development of antibiotics. We report here the total synthesis of xenocoumacin 1, a natural product that binds to 16S ribosomal RNA at a highly conserved region, as well as analogues thereof. Preliminary structure–activity relationship studies were aimed at understanding and modulating the selectivity between eukaryotic and prokaryotic ribosomes. Modifications were mainly tolerated in the aromatic region. Whole-cell activity against Gram-negative bacteria is limited by efflux and penetration, as demonstrated in genetically modified strains of E. coli. Analogues with high selectivity for eukaryotic ribosomes were identified, but it was not possible to obtain inhibitors selective for bacterial protein synthesis. Achieving high selectivity (albeit not the desired one) was thus possible despite the high homology between eukaryotic and prokaryotic ribosomes in the binding region.
View MoreZibo Kunran Enterprises Co. LTD
website:http://www.kunranchem.com
Contact:0086 533 5200669
Address:No. 96 Jinjing Avenue, Zibo, Shandong, China
Suzhou Credit International Trading Co., Ltd
Contact:+86-512-65398039
Address:Qingdeng, Hightech. District, Suzhou
Daicel Chiral Technologies (China)CO.,LTD
Contact:021-5046-0086*8
Address:Part C, FL 5, the 16th Building, No. 69, XiYa Road, WaiGaoQiao Free Trade Zone, Shanghai, 200131, P.R.China
RongCheng Tianyu Technology Co.,Ltd.
Contact:86-631-7519595
Address:220Ping Donghai Road RongChengCity,ShangDong Province China
Nanjing Zelang Medical Technology Co. Ltd
Contact:86-25-83063290/13770714480
Address:Ganjiabian 108# 01 Unit,701-702 room,Yao Hua Street,Qixia District,Nanjing,Jiangsu,China
Doi:10.1021/ja972281p
(1998)Doi:10.1039/b007270m
(2000)Doi:10.1039/b717754b
(2008)Doi:10.1021/ja801007q
(2008)Doi:10.1002/anie.200704586
(2008)Doi:10.1021/ol8007952
(2008)