Intramolecular [2+2] Photocycloaddition of Altrenogest: Confirmation of Product Structure, Theoretical Mechanistic Insight, and Bioactivity Assessment.
While studying the environmental fate of potent endocrine-active steroid hormones, we observed the formation of an intramolecular [2+2] photocycloaddition product (2) with a novel hexacyclic ring system following photolysis of altrenogest (1). The structure and absolute configuration were established by X-ray diffraction analysis. Theoretical computations identified a barrierless two-step cyclization mechanism for the formation of 2 upon photoexcitation. 2 exhibited progesterone, estrogen, androgen, and pregnane X receptor activity, albeit generally with reduced potency relative to 1.
The Journal of Organic Chemistry
post-print (with 12 month embargo)
Open Access Status
Kolodziej, Edward P.; Pflug, Nicholas C.; Patterson, Eric V.; Martinovic-Weigelt, Dalma; Gloer, James B.; McNeill, Kristopher; Cwiertny, David M.; and Wammer, Kristine H., "Intramolecular [2+2] Photocycloaddition of Altrenogest: Confirmation of Product Structure, Theoretical Mechanistic Insight, and Bioactivity Assessment." (2019). SIAS Faculty Publications. 1091.