1977/01/01 by Isabella Ferrara, Gleb A. Chesnokov, Silvia Dittmann +4 · 1 voice
Biochemistry, Genetics and Molecular Biology · Psychology · #ATP Synthase and ATPases Research #Antibiotic Resistance in Bacteria #Human Resource Development and Performance Evaluation #RNA and protein synthesis mechanisms
paper · pdf · doi:10.1021/jacsau.4c00206
openalex publication_date 1977/01/01 · openalex created_date 2016/06/24 · openalex updated_date 2026/06/24
Fidaxomicin (Fdx) constitutes a glycosylated natural product with excellent antibacterial activity against various Gram-positive bacteria but is approved only for <i>Clostridioides difficile</i> infections. Poor water solubility and acid lability preclude its use for other infections. Herein, we describe our strategy to overcome the acid lability by introducing acid-stable S-linked glycosides. We describe the direct, diastereoselective modification of unprotected Fdx without the need to avoid air or moisture. Using our newly established approach, Fdx was converted to the single atom exchanged analogue S-Fdx, in which the acid labile O-glycosidic bond to the noviose sugar was replaced by the acid stable S-glycosidic bond. Studies of the antibacterial activity of a structurally diverse set of thioglycoside derivatives revealed high potency of acyl derivatives of S-Fdx against <i>Clostridioides difficile</i> (MIC range: 0.12-4 μg/mL) and excellent potency against <i>Clostridium perfringens</i> (MIC range: 0.06-0.5 μg/mL).