121st General Meeting of the KCS

Type Poster Presentation
Area Organic Chemistry
Room No. Event Hall
Time 4월 19일 (목요일) 11:00~12:30
Code ORGN.P-499
Subject An effort to develop a simple synthetic method for direct functionalization of catechol-containing siderophores
Authors Juhui Jeong, Hak Joong Kim1,*
Chemistry, Korea University, Korea
1Department of Chemistry, Korea University, Korea
Abstract Siderophores are small molecule iron-chelators secreted by microorganisms in response to iron limitation. When pathogens infect a human, they utilize siderophores to intercept the iron in the infected host system to thrive. In this regard, siderophores are considered as important virulence factors, which has rendered the mechanisms associated with siderophore metabolism as viable antibiotic targets. Among various approaches, a Trojan horse strategy in which siderophores are utilized as antibiotic delivery vectors has attracted great attentions, because of its potential to overcome the drug permeability barrier, one of the major drug resistance mechanisms. For discovery of a potent siderophore-based antibiotic delivery system, it is crucial to establish an efficient synthetic method to derivatize siderophore molecules. By now, most siderophore modifications have involved the incorporation of a functional group compatible for a conjugation chemistry at the early stage of the synthesis, followed by progressive build-up of the siderophore scaffold. Such a conventional approach inevitably requires lengthy synthetic steps and, therefore, not suitable for rapid generation of siderophore-antibiotic conjugate library. To address this issue, this study has aimed to develop a simple synthetic method that allows direct functionalization of siderophores. Specifically, we have hypothesized that oxidation of the catechol moiety found in many siderophores (i.e., enterobactin, acinetobactin, etc.) to the corresponding ortho-benzoquinone followed by a site-selective nucleophilic addition of an antibiotic-containing fragment would allow us to achieve this goal. This presentation will entail some of our early results including the screening of various reaction conditions as well as preliminary evaluation of the substrate scope.
E-mail jungjuhee26@naver.com