A Natural Dihydropyridazinone Scaffold Generated from a Unique Substrate for a Hydrazine-Forming Enzyme

Nitrogen-nitrogen bond-containing functional groups are rare, but they are found in a considerably wide class of natural products. Recent clarifications of the biosynthetic routes for such functional groups shed light onto overlooked biosynthetic genes distributed across the bacterial kingdom, highlighting the presence of yet-to-be identified natural products with peculiar functional groups. Here, the genome-mining approach targeting a unique hydrazine-forming gene led to the discovery of actinopyridazinones A (1) and B (2), the first natural products with dihydropyridazinone rings. The structure of actinopyridazinone A was unambiguously established by total synthesis. Biosynthetic studies unveiled the structural diversity of natural hydrazines derived from this family of N-N bond-forming enzymes.

Automated summary

Functional groups containing nitrogen-nitrogen bonds are uncommon but can be found in a wide range of natural products. Recent research on the biosynthetic pathways of these functional groups has revealed the presence of overlooked biosynthetic genes in bacteria, indicating the existence of unidentified natural products with unique functional groups.