New Synthesis of 2-Hydroxyestrogen 2-Monoglucuronides

New synthetic routes leading to catechol estrogen 2-monoglucuronides are described. Selective introduction of a glucuronyl residue into the C-2 hydroxyl group was undertaken by utilizing a steric interaction of the 3-hydroxyl group with a bulky substituent at C-4. For this purpose, 4-bromo-2-hydroxyestriol 16, 17-diacetate was used as a key intermediate. The Koenigs-Knorr reaction of this catechol with methyl α-acetobromoglucuronate in the presence of cadmium carbonate proceeded preferentially toward the C-2 hydroxyl group. Subsequent reductive dehalogenation followed by alkaline hydrolysis provided the desired 2-hydroxyestriol 2-glucuronide. In a similar fashion, 2-hydroxyestradiol and-2-hydroxyestrone 2-glucuronides were also prepared.