Elsevier

Bioorganic Chemistry

Volume 31, Issue 2, April 2003, Pages 191-197
Bioorganic Chemistry

Convenient syntheses of biogenic aldehydes, 3,4-dihydroxyphenylacetaldehyde and 3,4-dihydroxyphenylglycolaldehyde

https://doi.org/10.1016/S0045-2068(03)00019-1Get rights and content

Abstract

The title compounds were prepared from a common precursor, a bis-THP-protected dihydroxyphenylacetic acid methyl ester. Key steps are the introduction of the α-hydroxyl group by Davis oxaziridine reagent and formation of the aldehydes by DIBALH ester reduction.

Introduction

As the primary mechanism of deactivation, monoamine neurotransmitters are metabolized to the corresponding aldehydes by monoamine oxidase (MAO)-catalyzed deamination within the nerve terminal. 3,4-Dihydroxyphenylacetaldehyde (dopal) is produced by the action of MAO on dopamine and 2-(3,4-dihydroxyphenyl)-2-hydroxyacetaldehyde (dopegal) is formed by MAO deamination of norepinephrine. The oxidative deactivation of the amines is key to maintenance of proper concentrations of these neurotransmitters. The further degradation of the aldehydes, either through further oxidation to acid metabolites or reduction to the corresponding alcohols is an important subsequent process. There is substantial evidence that high concentration of reactive aldehydic metabolites may be detrimental, since these can undergo non-enzymatic reactions with a number of compounds normally present in the CNS. Examples include Pictet–Spengler reactions with biogenic amines to form tetrahydroisoquinolines or Schiff base formation with endogenous amines such as lysine residues [1]. Recent reports provide evidence for the selective toxicity of both dopal [2] and dopegal [3]. As part of our research to study these reactions and to examine the appearance of the biogenic aldehydes under pathological conditions, we had need for authentic samples of dopal and dopegal, synthetic routes to which have been published [4], [5]. We report herein alternative convenient procedures for the preparation of these compounds. The convenience of the syntheses together with the importance of these compounds prompt us to publish our alternative procedures.

Section snippets

Results and discussion

A recent report describes the preparation of dopal from piperanal using a Darzens glycidic ester synthesis, as well as its complete characterization [4]. We have chosen a different approach that involves reduction of carboxylic ester to carbanal in a substrate possessing the requisite carbon framework, thus obviating the carbon–carbon bond-forming step. DIBALH reduction of readily available bis-THP-protected 3,4-dihydroxyphenylacetic acid methyl ester (5) proceeded in high yield to give

Conclusion

We describe an efficient and convenient synthesis of the biologically important aldehydes, dopal, and dopegal. The chemical procedures are simple, and the yields are satisfactory. In addition to the simplicity of this procedure, we avoid the use of environmentally unfriendly mercuric salts that were required in a previous synthesis of dopegal.

Experimental

All the reagents were from Aldrich and used without further purification. NMR spectra were run in CDCl3 or DMSO-d6 on a Varian Gemini 300 MHz spectrometer. Mass spectra were determined in Jeol SX-102 instrument. Infra red spectra were recorded in BioRad Win FTIR instrument.

Acknowledgments

The authors thank Wesley L. White and Victor Livengood for providing NMR and Mass Spectra, respectively.

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