In an ongoing effort to study the environmental fate of potent, endocrine-active steroid hormones, we report the formation of unusual phenolic rearrangement products (3 and 4) with a novel 6,5,8,5-ring system following aqueous photolysis of the pharmaceutical dienone steroids dienogest (1) and methyldienolone (2). The structures of 3 and 4 were established by analysis of 2D NMR and HRMS data, while the absolute configuration of 3 was determined by X-ray diffraction analysis. In vitro progesterone and androgen receptor transcriptional activation assays revealed that photoproducts exhibit progestogenic and androgenic activity (low-µM to sub-nM EC50 values), albeit lower than their respective parent compounds. Although 3 is a minor primary photoproduct of 1, we demonstrate its enrichment across several diurnal (i.e., light-dark) cycles because of the reversible photohydration of 1. The unusual structure and atypical route to environmental accumulation of 3 may result in previously unrecognized adverse ecological consequences associated with dienogest release into the environment.

Unusual bioactive rearrangement products from aqueous photolysis of pharmaceutical steroids and their enrichment through diurnal light-dark cycling

2019 Spring National Meeting

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