Photo-DHEA—A functional photoreactive dehydroepiandrosterone (DHEA) analog

[Display omitted] ▶ Design and synthesis of a photoreactive dehydroepiandrosterone (DHEA) analog. ▶ Photo-DHEA is cell biologically active. ▶ Photo-DHEA is the first photolabile DHEA derivative with an unaltered DHEA core. ▶ Photo-DHEA is suitable for radioiodination for identification of DHEA receptor(s). The steroid hormone dehydroepiandrosterone (DHEA) has beneficial effects on vascular function, survival of neurons, and fatty acid metabolism. However, a specific receptor for DHEA has not been identified to date. Here, we describe the synthesis of a photoreactive DHEA derivative (Photo-DHEA). In Photo-DHEA, typical characteristics of DHEA are conserved: (i) a “planar” tetracyclic ring system with a Δ 5 double bond, (ii) a 3β-hydroxyl group, and (iii) a keto group at C17. In cell-based assays, Photo-DHEA showed the same properties as DHEA. We conclude that Photo-DHEA is suitable for radioiodination to yield a tool for the identification of the elusive DHEA receptor.