The Discovery of Complex Heterocycles from Millipede Secretions

The recent explosion in documented chemistry from Colobognatha, a millipede subterclass with more than 240 species, has rekindled interest in the defensive secretions from these ancient animals. Prior to 2020, studies on defensive secretions by Colobognatha─the only millipedes that produce terpenoid alkaloids─were limited to a single order, Polyzoniida. However, numerous species of the order Platydesmida have recently been shown to produce structurally diverse terpenoid alkaloids with potent biological activities. Platydesmidan defensive secretions encompass multiple natural product scaffolds with greater chemical complexity compared to previously reported millipede-derived alkaloids. Here, we report an analysis of the defensive secretions of Andrognathus corticarius, an evolutionary sister to all other Platydesmida. Analyzing defensive secretions revealed that A. corticarius produces an arsenal of alkaloids dissimilar to all previously reported metabolites. Using various analytical techniques, we accomplished complete structural assignment of two distinct scaffolds: a 5,6-fused heterocycle named the andrognathines and a 6,6,6,5-bridged heterocycle containing seven continuous stereogenic centers named the andrognathanols. Each scaffold contains diverse fatty acids; this leads to an extraordinary number of unique metabolites. These described alkaloids are actively secreted upon physical disturbance and change the behavior of ants that reside in the same environment.