Absolute Configuration and Docking Study of Canescensterone, a Potent Phytoecdysteroid, with Non-Lepidopteran Ecdysteroid Receptor Selectivity

The rare phytoecdysteroid canescensterone is a potent activator of both natural and engineered ecdysteroid receptor (EcR) gene-expression systems. This steroid also shows a remarkable selectivity towards non-lepidopteran compared with lepidopteran EcRs in gene-switch assays, a property that makes it a novel candidate lead compound for use in insecticide discovery and gene-switch design. Canescensterone possesses an unusual ecdysteroid structure, including a pyrrole-2-carboxylate group attached to C-24, a moiety not yet found in any other natural ecdysteroid. We have investigated the ambiguous stereochemistry at C-24 of this steroid by 1D and 2D solution NMR experiments, which resulted in the assignment of the 24R-configuration and determination of the side-chain conformation. The complete stereochemical assignment allowed the generation of docking models of canescensterone in both a lepidopteran EcR and a non-lepidopteran EcR, which helps to explain its selective biological activity.