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Organic Letters, 2020.22(7), 2806-2810, DOI: https://doi.org/10.1021/acs.orglett.0c00790
Total Syntheses of Fimsbactin A and B and Their Stereoisomers to Probe the Stereoselectivity of the Fimsbactin Uptake Machinery in Acinetobacter baumannii
Soojeong Kim, Haeun Lee, Woon Young Song, Hak Joong Kim*
Background: Fimsbacitn is one of the siderophores utilized by Acinetobacter baumannii for iron acquisition, but the investigation regarding this molecule has rarely been investigated. In this regard, this study intended to establish a synthetic method for its preparation and, at the same time, to investigate the relationship between its structure, particularly with respect to the stereochemistry, with its cellular uptake.
Materials and methods: For syntheses of fimsbactin and its analogues, various organic reactions were utilized. The evaluation of their biological activities were conducted based on the monitoring of their growth stimulating activities for A. baumannii cultured under iron-deficient conditions.
Results: By further streamlining the existing method for fimsbactin B synthesis reported by our laboratory earlier, the stereoselective synthetic method for fimsbactin A could be successfully established for the first time, and using this method a number of stereoisomers thereof were prepared. Then, the investigation of their growth stimulating activities for A. baumannii revealed that the cognate uptake machinery on this bacterium is indeed highly stereoselective.
Conclusions: This study not only established an effective way to synthesize fimsbactin and its analogues, essential for future development of novel fimsbactin-based therapeutics, but also confirmed the chracteristic substrate specificity of the fimsbactin uptake machinery on A. baumannii. Keywords: siderophore, synthesis of fimsbactin, stereoselectivity of the fimsbactin uptake machinery
- DOI: https://doi.org/10.1021/acs.orglett.0c00790
- ISBN or ISSN: 1523-7060
- 본 연구는 질병관리본부 연구개발과제연구비를 지원받아 수행되었습니다.
- This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention.