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Synthesis of morphine‐[ N ‐methyl‐ 14 C]‐6‐ β ‐ D ‐glucuronide
Author(s) -
Ferguson John R.,
Hollis Stephen J.,
Johnston Grant A.,
Lumbard Keith W.,
Stachulski Andrew V.
Publication year - 2002
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.540
Subject(s) - chemistry , glucuronide , morphine , glucuronidation , potassium hydroxide , hydrochloride , hydrolysis , alkaline hydrolysis , alkylation , chromatography , organic chemistry , metabolite , pharmacology , enzyme , biochemistry , microsome , catalysis , medicine
Protected morphine‐6‐glucuronide was converted into morphine‐[ N ‐methyl‐ 14 C]‐6‐glucuronide by a three‐step procedure. Methyl (3‐pivaloylmorphin‐6‐yl 2,3,4‐tri‐ O ‐isobutyryl‐ β ‐D‐glucopyranosid)uronate was N‐demethylated by treatment with 1‐chloroethyl chloroformate to afford protected normorphine‐6‐glucuronide as its hydrochloride salt. The normorphine‐6‐glucuronide derivative was alkylated with iodomethane‐[ 14 C] in the presence of potassium carbonate to produce C‐14 labelled protected morphine‐6‐glucuronide. Finally, hydrolysis of the protecting groups using 5% sodium hydroxide solution gave morphine‐[ N ‐methyl‐ 14 C]‐6‐ β ‐D‐glucuronide with a specific activity of 41.8 mCi mmol −1 and radiochemical purity of 99.2% (HPLC). Copyright © 2002 John Wiley & Sons, Ltd.