Journal of Labelled Compounds and Radiopharmaceuticals
J Label Compd Radiopharm 2007; 50: 475–476.
Published online in Wiley InterScience
JLCR
(www.interscience.wiley.com). DOI: 10.1002/jlcr.1204
Short Research Article
Deuteration of dietary antioxidants: ferulic acid derivatives
y
and a-tocopherol
¨
¨ ¨
KIRSTI PARIKKA and KRISTIINA WAHALA*
Laboratory of Organic Chemistry, Department of Chemistry, University of Helsinki, P.O. Box 55, 00014-University of Helsinki, Finland
Received 29 June 2006; Revised 22 November 2006; Accepted 23 November 2006
Keywords: deuterium labeling; ferulic acid; a-tocopherol
Introduction
We have sought a simple and efficient synthesis for
the deuterated ferulic acid derivatives 1–3 and
a-tocopherol 4. Stable and pure deuterated analogues
are required for the development of quantitative
analysis and for metabolic studies.
The potential health benefits of ferulic acid and other
hydroxycinnamates have raised interest in recent
years. These phenolic acids can be found in the human
1
diet, e.g. in cereal brans. Ferulic acid has been
reported to have biological activities such as antiox-
idant, antimicrobial, anti-inflammatory, antithrombo-
sis and anticancer properties. Investigation of the
antioxidant properties have shown ferulic acid to have
high scavenging activity for hydrogen peroxide, super-
Results and Discussion
Deuterated ferulic acids were prepared starting from 3,4-
dihydroxybenzaldehyde which was selectively methylated
with CD I. Products were either [D ]vanillin or [D ]iso-
3
3
3
2
oxide, hydroxyl radical and other oxidative species.
vanillin depending on the base and solvent used in the
reaction and the reaction time. These intermediates were
alkylated by the Doebner modification of Knoevenagel
condensation under microwave irradiation giving both
ferulic acids in good yield (Scheme 1).
Another dietary antioxidant is a-tocopherol which
belongs to the vitamin E family. Tocopherols are
present in oil seeds, leaves and other green parts of
higher plants. Vitamin E is the most important fat-
soluble antioxidant having various beneficial effects
including protection against cancer, cardiovascular
diseases, free radical induced damage on cell
membrane and DNA and oxidation of low density
For deuterated a-tocopherol, we applied microwave
enhancement of the synthesis starting from d-toco-
4
pherol (Scheme 2). Reaction time was shortened from
4 hours to less than half an hour and reduced amounts
of reagents were needed.
3
lipoproteins.
*
Correspondence to: Kristiina W a¨ h a¨ l a¨ , Laboratory of Organic Chem-
istry, Department of Chemistry, University of Helsinki, P.O. Box 55,
0014-University of Helsinki, Finland.
0
E-mail: kristiina.wahala@helsinki.fi
y
Proceedings of the Ninth International Symposium on the Synthesis
and Applications of Isotopically Labelled Compounds, Edinburgh,
1
6–20 July 2006.
Copyright # 2007 John Wiley & Sons, Ltd.