SYNTHESIS OF N-ACETYLCYSTEINE CONJUGATES OF CATECHOL ESTROGENS

The synthesis of N-acetylcysteine, conjugates of 2-hydroxyestrone (2-O HE(1)) and 4-hydroxyestrone (4-OHE(1)) is described. The reaction of e strone 2,3-quinone with N-acetylcysteine provided 2-OHE(1) and its C-4 and C-1 thioether conjugates in a ratio of 1:1, while estrone 3,4-qui none with N-acetylcysteine gave 4-OHE(1) and its C-2 thioether conjuga te as a sole product. Their structures were characterized by inspectio n of NMR spectra, chemical derivatization (methylation and acetylation ), and comparison with the reactivity of 4-bromoestrone 2,3-quinone or 2-bromoestrone 3,4-quinone toward N-acetylcysteine.