Syntheses of estetrol monoglucuronides.
Four possible monoglucuronides of estetrol (estra-1,3,5(10)-triene-3,15 alpha, 16 alpha, 17 beta-tetraol) have been prepared from appropriately protected estetrol by the Koenigs-Knorr reaction employing cadmium carbonate as a catalyst. Condensation of methyl acetobromoglucuronate with estetrol 15,16,17-triacetate provided the 3-glucuronide acetate-methyl ester in a satisfactory yield. Introduction of the glucuronyl residue into C-17 was similarly attained by the use of estetrol 3-benzoate 15,16-acetonide. When estetrol 3,17-diacetate and acetobromosugar were stirred in anhydrous toluene in the presence of cadmium salt, the reaction occurred at C-16 and C-15 yielding two isomeric monoglucuronide derivatives in a ratio of ca. 5 to 2. Removal of the protecting groups in the four glucuronide acetate-methyl esters gave the desired estetrol glucuronides, respectively. These synthetic substrates underwent readily enzymatic hydrolysis with beef-liver beta-glucuronidase to afford estetrol.
D000818:Animals; D002104:Cadmium; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D004953:Estetrol / Q000138:chemical synthesis*; D004964:Estriol / Q000031:analogs & derivatives*; D005965:Glucuronates / Q000138:chemical synthesis; D005966:Glucuronidase; D006868:Hydrolysis; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D008722:Methods
D005965:Glucuronates; D002104:Cadmium; D005966:Glucuronidase; D004953:Estetrol; D004964:Estriol