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General methods for the synthesis of methyl isotope labelled catecholamine metabolites. Preparation of 4‐hydroxy‐3‐methoxy‐d 3 ‐ (mandelic acid, phenylacetic acid, and phenylethylene glycol)
Author(s) -
Markey S. P.,
Powers K.,
Dubinsky D.,
Kopin I. J.
Publication year - 1980
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.2580170111
Subject(s) - chemistry , mandelic acid , phenylacetic acid , sodium borohydride , hydrogenolysis , catechol , organic chemistry , methyl iodide , alkylation , malic acid , medicinal chemistry , catalysis , citric acid
Two general schemes for the synthesis of isotope labelled monomethyl catecholamine metabolites are described. Catechol was converted to 2‐methoxy‐d 3 ‐phenol (2) with deuteromethyl iodide and reacted with sodium glyoxylate to form 4‐hydroxy‐3‐methoxy‐d 3 ‐mandelic acid (3). Hydrogenolysis of the methyl ester‐diacetate of 3 with excess sodium borohydride in water yielded 4‐hydroxy‐3‐methoxy‐d 3 ‐phenylacetic acid (4). Reduction of 3 with diborane produced 4‐hydroxy‐3‐methoxy‐d 3 ‐phenylethylene glycol (5). An alternative route was to alkylate 3,4‐dihydroxybenzaldehyde (6) and produce 3 or its 3‐hydroxy‐4‐methoxy isomer via the nitrile mandelic acid synthesis. Suitability of these isotopic and isomeric variants as internal standards for quantitation by gas chromatography‐mass spectrometry is discussed.