SYNTHESIS OF 15-ALPHA-HYDROXYESTROGEN 15-N-ACETYLGLUCOSAMINIDES

The synthesis of 15-N-acetylglucosaminides of 15 alpha-hydroxyestrone, 15 alpha-hydroxyestradiol, and 15 alpha-hydroxyestriol (estetrol) is described. The latter two were prepared by condensation of 2-acetamido -1 ro-1,2-dideoxy-3,4,6-trio-O-acetyl-D-glucopyranose with appropriate ly protected 15 alpha-hydroxyestrogens by the Koenigs-Knorr reaction e mploying cadmium carbonate as a catalyst. Subsequent removal of protec ting groups with methanolic potassium hydroxide provided the desired c onjugates. 15 alpha-Hydroxyestrone 15-N-acetylglucosaminide was synthe sized from the corresponding 15 alpha-hydroxyestradiol derivative by J ones oxidation followed by brief alkaline hydrolysis. These conjugates underwent enzymatic hydrolysis with beta-N-acetylglucosaminidase from Jack beans to produce 15 alpha-hydroxyestrogens.