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Aldosterone Glucuronide, an Important Biomarker: Synthesis and Structure Elucidation of Novel Isomers
Author(s) -
Guha Somraj,
Senthilkumar Soundararasu,
Voß Edgar,
Tietze Lutz F.
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202004154
Subject(s) - glucuronate , aldosterone , glucuronide , chemistry , glucuronates , trimethylsilyl , stereochemistry , glucuronic acid , medicinal chemistry , organic chemistry , medicine , metabolism , biochemistry , polysaccharide
Abstract 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 BF 3 ⋅OEt 2 . 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.