ISSN 1214-0287 (on-line)
ISSN 1214-021X (printed)

Volume 5 (2007), No 1, p 13-17

Convenient synthesis of 3,5-dialkoxy-4-hydroxy cinnamic acids

Young-Sik Jung, Hyang-Ok Jo

Address: Medicinal Science Division, Korea Research Institute of Chemical Technology, P. O. Box 107, Yusong, Daejeon 305-606, Korea

Received 25th October 2006.
Revised 10th November 2006.
Published online 4th December 2006.

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3,5-Dialkoxy-4-hydroxy cinnamic acids 8a-g have been conveniently synthesized from methyl 4-benzyloxy-3,5-dihydroxybenzoate 4. In five steps, cinamic acids 8a-g having various alkoxy groups on C-3 and C-5 positions of the phenyl ring were obtained in 33-70% overall yields. The antioxidant properties of the newly synthesized amides and the effects on lipid peroxidation in rat brain homogenate will be examined by thiobarbituric acid reactive substances (TBARS) assay and other methods.

3,5-dialkoxy-4-hydroxy cinnamic acids; dialkylation; lipid peroxidation

Chance B, Sies H, Boveris A: Hydroperoxide metabolism in mammalian organs. Physiol Rev 59:527-605, 1979.

Clemens JA: Cerebral ischemia: gene activation, neuronal injury, and the protective role of antioxidants. Free Radic Biol Med 28:1526-1531, 2000.

Halliwell B, Gutteridge JMC: Free Radicals in Biology and Medicine, 3rd ed.; Oxford University Press 1999, pp. 246-350.

Harrison SC, Lynch JJ, Rose K, Choi DW: Trolox attenuates cortical neuronal injury induced by iron, ultraviolet light, glucose deprivation, or AMPA. Brain Res 639:102-108, 1994.

Hersmis MC, Spiering AJH, Waterval RJM, Meuldijk J, Vekemans JAJM, Hulshof LA: 3,4,5-Tri-dodecyloxybenzoic acid: Optimisation and scale-up of the synthesis. Org Process Res Dev 5:54-60, 2001.

Jung YS, Kang TS, Yoon JH, Joe BY, Lim HJ, Seong CM, Park WK, Kong JY, Cho J, Park NS: Synthesis and evaluation of 4-hydroxyphenylacetic acid amides and 4-hydroxycinnamamides as antioxidants. Bioorg Med Chem Lett 12:2599-2602, 2002.

Keyser JD, Sulter G, Luiten PG: Clinical trials with neuroprotective drugs un acute ischemic stroke: are we doing the right thing? Trends Neurosci 22:535-540, 1999.

Kingsbury CA, Max G: Substituent effects on bromodecarboxylation reactions. J Org Chem 43:3131-3139, 1978.

Mannekens E, Tourwe D, Lubell WD: Efficient synthesis of 1-benzyloxyphenyl-3-phenylacetones. Synthesis 1214-1216, 2000.

Yamaguchi T, Sano K, Takakura K, Saito I, Shinohara Y, Asano T, Yasuhara H: Ebselen in acute ischemic stroke: A placebo-controlled, double-blind clinical trial. Strokes 29:12-17, 1998.

Yu MJ, McCowan JR, Phebus LA, Towner RD, Ho PPK, Keith PT, Luttman CA, Saunders RD, Ruterbories KJ, Lindstrom TD, Wikel JH, Morgan E, Hahn RA: Benzylamine antioxidants: relationship between structure, peroxyl radical scavenging, lipid peroxidation inhibition and cytoprotection. J Med Chem 36:1262-1271, 1993.

Kang TS, Jo HO, Park WK, Kim JP, Konishi Y, Kong JY, Park NS, Jung YS: Synthesis and antioxidant activities of 3,5-dialkoxy-4-hydroxycinnamamides. Bioorg Med Chem Lett 18:1663-1667, 2008.