Total Synthesis of Mutanobactins A, B from the Human Microbiome: Macrocyclization and Thiazepanone Assembly in a Single Step

We report the first total syntheses of tricyclic mutanobactins A and B, lipopeptides incorporating a thiazepanone, isolated from Streptococcus mutans, a member of the human oral microbiome. A rapid, solid-phase peptide synthesis (SPPS) based route delivers these natural products from a cascade of cyclization reactions. This versatile process was also employed in a streamlined synthesis of mutanobactin D. Additionally, we provide an independent synthesis of a truncated mutanobactin A analog, utilizing a novel thiazepanone amino acid building block.

Automated summary

The first total syntheses of tricyclic mutanobactins A and B, lipopeptides incorporating a thiazepanone, isolated from Streptococcus mutans, a member of the human oral microbiome, were reported. These natural products were rapidly delivered through a cascade of cyclization reactions using a solid-phase peptide synthesis (SPPS) based route. This versatile process was also used for a streamlined synthesis of mutanobactin D. Additionally, an independent synthesis of a truncated mutanobactin A analog, utilizing a novel thiazepanone amino acid building block, was provided.