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Intramolecular [2 + 2] Photocycloaddition of Altrenogest: Confirmation of Product Structure, Theoretical Mechanistic Insight, and Bioactivity Assessment

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journal contribution
posted on 20.08.2019, 18:36 by Nicholas C. Pflug, Eric V. Patterson, Dalma Martinović-Weigelt, Edward P. Kolodziej, James B. Gloer, Kristopher McNeill, David M. Cwiertny, Kristine H. Wammer
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 the 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.