Silkenath Bjarne, Kläge Dennis, Eppelin Philip, Hartig Jörg S, Wittmann Valentin
Department of Chemistry, University of Konstanz, 78457 Konstanz, Germany.
J Org Chem. 2025 Feb 28;90(8):2969-2977. doi: 10.1021/acs.joc.4c02816. Epub 2025 Feb 15.
Carba-sugars─carbohydrate mimics in which the ring oxygen is replaced by a methylene group─are carbohydrate analogues of natural or synthetic origin that can have important biological functions. Especially, carba-aminosugars and glycosides containing carba-aminosugars are potent antibiotics. Furthermore, they have been shown to induce the self-cleavage reaction of the riboswitch and thereby inhibit the ability of bacteria to synthesize glucosamine-6-phosphate, which is required to build up the bacterial cell wall. We report the synthesis of a library of 20 carba-glucosamine derivatives with various substituents at the carba-position including amines, alkyl, alkoxy, and aryloxy derivatives, fluorine derivatives, glycosylated derivatives, and a cyclopropane derivative. The compounds were obtained in an efficient way starting from late-stage synthetic intermediates of an earlier-developed synthesis of carba-substituted carba-glucosamines. All carba-glucosamine mimics were tested for their antibacterial properties against , and some of them displayed promising activities in a filter disk assay.
碳环糖——一种环中的氧原子被亚甲基取代的碳水化合物类似物——是天然或合成来源的碳水化合物类似物，具有重要的生物学功能。特别是，碳环氨基糖和含有碳环氨基糖的糖苷是强效抗生素。此外，它们已被证明能诱导核糖开关的自切割反应，从而抑制细菌合成6-磷酸葡糖胺的能力，而6-磷酸葡糖胺是构建细菌细胞壁所必需的。我们报道了一个包含20种碳环葡糖胺衍生物的文库的合成，这些衍生物在碳环位置具有各种取代基，包括胺基、烷基、烷氧基和芳氧基衍生物、氟衍生物、糖基化衍生物和环丙烷衍生物。这些化合物是从早期开发的碳环取代的碳环葡糖胺合成的后期合成中间体开始，通过高效的方法获得的。所有碳环葡糖胺模拟物都针对[具体细菌名称未给出]测试了其抗菌性能，其中一些在滤纸片法中显示出有前景的活性。
