The glmS-riboswitch is a new target to fight multi-resistant bacterial strains. This RNA segment is encoding for the glucosamine-6-phosphate synthase (GlmS) that is essential for the formation of glucosamine-6-phosphate (GlcN6P), an important building block in the early steps of the bacterial cell wall biosynthesis . At elevated concentrations, GlcN6P can bind to the aptamer region of the glmS-riboswitch and induce a self-cleavage reaction. Eventually, the RNA segment is degraded and the formation of GlmS is stopped.
Previously, we could show that carba-sugar derivatives of GlcN6P are able to bind to the glmS-riboswitch and induce the self-cleavage reaction . Here, we present the synthesis of novel carba-sugar derivatives 7 of GlcN6P that are substituted at the carba position (Scheme 1). The key steps of this synthesis route are a ring-closing metathesis (RCM) reaction (3 → 4) and a hydroboration (4 → 5) that results in key intermediate 5. Further derivatization by alkylation and phosphorylation yields 7. The activity of the synthesized compounds in the self-cleavage reaction of the glmS-riboswitch, as evaluated by biological in-vitro self-cleavage assays, is presented.
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