General methods for the synthesis of methyl isotope labelled catecholamine metabolites. Preparation of 4-hydroxy-3-methoxy-d3- (mandelic acid, phenylacetic acid, and phenylethylene glycol)
✍ Scribed by S. P. Markey; K. Powers; D. Dubinsky; I. J. Kopin
- Publisher
- John Wiley and Sons
- Year
- 1980
- Tongue
- French
- Weight
- 405 KB
- Volume
- 17
- Category
- Article
- ISSN
- 0022-2135
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✦ Synopsis
Abstract
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.