Synthesis and estrogenic activity of bisphenol A mono‐ and di‐β‐D‐glucopyranosides, plant metabolites of bisphenol A

Abstract

The syntheses and characterization of bisphenol A mno‐ and di‐β‐D‐glucopyranosides were undertaken to confirm that these compounds are major plant metabolites of bisphenol A (BPA) and to allow an assessment of their estrogenicity. Synthesis involved the glucosidation of unprotected BPA with glucose penta‐acetate with phosphorus oxychloride as catalyst. The estrogenic activity of BPA and its mono‐ and di‐β‐D‐glucopyranosides were measured with an enzyme‐linked immunosorbent assay (ELISA)‐based estrogen receptor competitive binding assay and with a yeast two‐hybrid assay adapted to a chemiluminescent reporter gene (for β‐galactosidase). Both methods showed that the estrogenicity of BPA was eliminated by formation of the diglucoside, but whereas the ELISA‐based method indicated that reduced activity remained in the monoglucoside, the yeast two‐hybrid method showed the monoglucoside to be inactive. Presumably these results reflect the more complex interactions of test compound and cellular components required to demonstrate estrogenicity in the yeast two‐hybrid assay. As these processes parallel those in mammalian cells, the yeast two‐hybrid method is likely to be the more realistic assay. The uptake and metabolism of BPA by plants offers the possibility of phytoremediation of contaminated water, but also provides an additional route for the compound to enter the human food chain.