A Concise Synthesis of Carolacton

ABSTRACT: A synthesis of carolacton, a myxobacterial natural product that has profound effects on Streptococcus mutans biofilms, is reported. The synthesis proceeds via a longest linear sequence of 14 steps from an Evans β-ketoimide and enabled preliminary evaluations of the effects of late-stage intermediates on S. mutans biofilms. These studies suggest that further investigations into carolacton’s structure−function relationships are warranted. Dental caries is a chronic health problem that impacts themajority of the global population.1 Although culture-independent sequencing has illuminated the complexity of the human oral microbiome, Streptococcus mutans remains widely regarded as a primary etiological agent in caries.2,3 This facultatively anaerobic, microaereophilic, Gram-positive, bacte-rium excels in the complex environment of the oral cavity where stresses including low pH and an oxidative environ-ment are coupled to variable salivary flow and carbohydrat