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

Abstract

Aldosterone 1 is am ineralocorticoid, it has great influence on the blood pressure and its glucuronide is an important marker for the detection of several diseases.H ere, we describe the chemical synthesis of different aldosterone-18-and 20-glucuronides. Reaction of trimethylsilyl 2,3,4-triacetyl-1-b-glucuronic acid methyl ester 5b and aldosterone diacetate 11 in the presence of TMSOTf gave the 18-a-glucuronide 9a.The 18-b-glucuronide 15 b and the 20-b-glucuronide 16 b could be obtained by reaction of methyl 2,3,4-triO -isobutyryl-1a-glucuronatet richloroacetimidate 14 and aldosterone 21-acetate 8 in the presence of TMSOTf or BF 3 •OEt 2 .F inally,r eaction of aldosterone 21-acetate 8 and methyl 2,3,4-triacetyl-1a-glucuronate trichloroacetimidate 19 in the presence of TMSOTf gave the corresponding methyl 18-b-triacetylglucuronate 9b,w hichw as transformed into the desired aldosterone-18-b-glucuronide 3 by two enzymatic transformations.