Honokiol-Inspired Analogs as Inhibitors of Oral Bacteria

The oral microbiome is a complex ecological niche where both commensal and pathogenic bacteria coexist. Previous reports have cited that the plant isolate honokiol is a potent inhibitor of <i>S. mutans</i> biofilms. Herein we report a cross-coupling method that provides access to a concise library of honokiol-inspired analogs. Through this work we determined that the inhibitory activity of honokiol is highly dependent on the growth conditions. Further, we identify a series of analogs that display significant potency against oral bacteria leading to the discovery of a potent antimicrobial

Diverted Total Synthesis of Carolacton-Inspired Analogs Yields Three Distinct Phenotypes in <i>Streptococcus mutans</i> Biofilms

The oral microbiome is a dynamic environment inhabited by both commensals and pathogens. Among these is Streptococcus mutans, the causative agent of dental caries, the most prevalent childhood disease. Carolacton has remarkably specific activity against S. mutans, causing acid-mediated cell death during biofilm formation; however, its complex structure limits its utility. Herein, we report the diverted total synthesis and biological evaluation of a rationally designed library of simplified analogs that unveiled three unique biofilm phenotypes further validating the role of natural product synthesis in the discovery of new biological phenomena