Steroid conjugates. VII. Preparation of N-acetylglucosaminides of 17α- and 17β-estradiol

Abstract

Condensation of 17/3-estradiol 3-benzyl ether (I) with 1 a-bromo-A-trifluoroacetamido tri-O-acetylglucopyranoside (Xb) in the presence of cadmium carbonate gave the corresponding 17/3-estradiol 17-(a-and /3-)glycosides (lib, III). Selective deacylation and reacetylation followed by debenzylation afforded the 17/3-estradiol 17-(a-and /3-)A-acetyl-T Xhe isolation of -estradiol 3-glucuronide 17/3-acetylglucosaminide from rabbit urine by Layne and coworkers (1964) revealed a new conjugating pathway for steroids. In a subsequent series of papers, Layne and coworkers (Jirku and Layne, 1965; Layne el al., 1965;Collins et al., 1967Collins et al., , 1968) studied C-l7-glucosaminide formation by the action of an A-acetylglucosaminyl-transfer enzyme system and showed that the stereochemical configuration of the Hahydroxyl group was a necessary structural feature for estrogens containing a C-3-glucuronide.Recently, other double conjugates containing a A-acetylglucosaminide grouping have been isolated from human urine.

Synthesis and Glycosidation of Anomeric Halides: Evolution from Early Studies to Modern Methods of the 21st Century

“…Cadmium sulfide was also investigated for the activation of donor 70 ; however, the yield of product 72 was only 20%. Several other steroidal phenolic glucuronides, glycosides, and acetyl glucosaminides were successfully synthesized using similar glycosylation conditions. ,, In addition to β-glycosides, small amounts of the corresponding α-glucosides and/or C -glycosides were also isolated, and the ratio of products was found to depend on the coupling partners and the reaction conditions employed. It was suggested that the generated cadmium bromide was the actual activator, but cadmium bromide by itself was ineffective, similar to Helfrich’s observations made with mercuric cyanide activation .…”

“…Cadmium sulfide was also investigated as the activator for the glycosidation of the anomeric chloride; however, the yield of the glucuronide was below the preparative value. Several other steroidal phenolic glucoronides, glycosides, and acetyl glucosaminides were successfully synthesized. ,, In addition to β-glycosides, a small amount of the corresponding α-glucosides and/or C -glycosides were also isolated, and the ratio of reagents was found to depend on coupling partners and reaction conditions employed. An interesting aspect of these reactions was the development of color as the reaction progresses.…”