Title
Intramolecular [2 + 2] Photocycloaddition of Altrenogest: Confirmation of Product Structure, Theoretical Mechanistic Insight, and Bioactivity Assessment
Department/School
Chemistry
Date
9-6-2019
Document Type
Article
DOI
https://doi.org/10.1021/acs.joc.9b02070
Abstract
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.
Published in
Journal of Organic Chemistry
Citation/Other Information
Pflug, N.C., E.V. Patterson, D. Martinovic-Weigelt, E.P. Kolodziej, J.B. Gloer, K. McNeill, D.M. Cwiertny, K.H. Wammer. 2019. "Intramolecular [2+2] photocycloaddition of altrenogest: confirmation of product structure, theoretical mechanistic insight, and bioactivity assessment." Journal of Organic Chemistry, 84:11366-11371. DOI: 10.1021/acs.joc.9b02070