Aldosterone Glucuronide,an Important Biomarker: Synthesis and Structure Elucidation of Novel Isomers

Aldosterone 1 is a mineralocorticoid, it has great influence on the blood pressure and its glucuronide is an important marker for the detection of several diseases. Here, we describe the chemical synthesis of different aldosterone-18- and 20-glucuronides. Reaction of trimethylsilyl 2,3,4-tri- acetyl-1-β-glucuronic acid methyl ester 5 b and aldosterone diacetate 11 in the presence of TMSOTf gave the 18-α-glucuronide 9 a . The 18-β-glucuronide 15 b and the 20-β-glucuronide 16 b could be obtained by reaction of methyl 2,3,4-tri-O-isobutyryl-1α-glucuronate trichloroacetimidate 14 and aldosterone 21-acetate 8 in the presence of TMSOTf or BF₃⋅OEt₂. Finally, reaction of aldosterone 21-acetate 8 and methyl 2,3,4-triacetyl-1α-glucuronate trichloroacetimidate 19 in the presence of TMSOTf gave the corresponding methyl 18-β-triacetylglucuronate 9 b , which was transformed into the desired aldosterone-18-β-glucuronide 3 by two enzyma- tic transformations.