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Application of the Bischler–Napieralski–Pschorr radiosynthesis of ( R )‐(‐)‐[6a‐ 14 C]apomorphine, a non‐selective D1/D2 dopamine receptor agonist
Author(s) -
Kitson Sean L.,
Knagg Eric
Publication year - 2006
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.1070
Subject(s) - chemistry , apomorphine , radiosynthesis , isoquinoline , agonist , medicinal chemistry , organic chemistry , receptor , biochemistry , microbiology and biotechnology , in vivo , biology
A method has been developed for the carbon‐14 radiosynthesis of non‐narcotic morphine derivative ( R )‐(‐)‐[6a‐ 14 C]apomorphine ( 1 ) from the starting material 3,4‐dimethoxy‐2‐nitrophenyl‐ N ‐phenethyl[carboxyl‐ 14 C]acetamide ( 5 ). The key to this synthesis was the application of the Bischler–Napieralski cyclodehydration to 1‐(3,4‐dimethoxy‐2‐nitrobenzyl)dihydro[1‐ 14 C]isoquinoline ( 4 ), followed by N ‐methylation and reduction to 1‐(3,4‐dimethoxy‐2‐nitrobenzyl)‐2‐methyl‐1,2,3,4‐tetrahydro[1‐ 14 C]isoquinoline ( 3 ). A final Pschorr reductive ring closure followed by chiral separation to give ( R )‐(‐)‐[6a‐ 14 C]apomorphine dimethyl ether ( 2 ) and O ‐demethylation led to ( R )‐(‐)‐[6a‐ 14 C]apomorphine ( 1 ) with a specific activity of 55 mCi/mmol, radiochemical purity of >98% and chiral purity of >99%. Copyright © 2006 John Wiley & Sons, Ltd.