Chemical Approach for Investigation of the Structure‐Activity Relationship of Salmycin and Identification of a Glycan‐based Analogue for Drug Resistant Staphylococcus aureus

New synthetic routes were devised for total synthesis of Fe3+‐bound (ferri−) salmycin B (Sal B) (1), glycan‐based Sal analogues 2–5 and their Fe3+‐unbound (desferri−) counterparts 1′–5′ for the structure to activity relationship (SAR) study. The results of SAR study reveal the effective structure of...

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Published in:	Advanced synthesis & catalysis 2024-01, Vol.366 (1), p.101-113
Main Authors:	Chiu, Cheng‐Hsin, Huang, De‐Yi, Ma, Wei‐Hsiang, Chen, Yu‐Xun, Yang, Sih‐Yu, Chen, Yu‐Chie, Tony Mong, Kwok‐Kong
Format:	Article
Language:	eng
Subjects:	Antiinfectives and antibacterials Glycan Glycan-based salmycin analogues Methicillin resistance Natural products Salmycin Staphylococcus aureus Troian-horse antibiotics Vancomycin
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Summary:	New synthetic routes were devised for total synthesis of Fe3+‐bound (ferri−) salmycin B (Sal B) (1), glycan‐based Sal analogues 2–5 and their Fe3+‐unbound (desferri−) counterparts 1′–5′ for the structure to activity relationship (SAR) study. The results of SAR study reveal the effective structure of 1 and its desferri‐counterpart 1′ that are responsible for the observed inhibitory activity against Staphylococcus aureus (S. aureus). Among the analogues 2–5 and 2′–5′, glucose‐based analogue 2 and its desferri‐counterpart 2′ exhibited inhibitory potency comparable to 1 and 1′. Chemical modification of 2′ for further antibacterial study enabled us to discover desferri‐Sal analogue 7′ that endowed with a simpler pharmacophore structure but significantly higher antibacterial potency against methicillin‐sensitive and resistant S. aureus than the natural product 1′ and even the clinical vancomycin. Together with a better hydrolytic stability and shorter synthetic route, the analogue 7′ represents an attractive antibiotic lead for further exploration.
ISSN:	1615-4150 1615-4169