Synthesis of D,L-2-Amino-3-(3,4-dihydroxyphenyl)propanoic Acid

Abstract

A method for the synthesis of 2-amino-3-(3,4-dihydroxyphenyl)propanoic acid (dioxyphenylalanine, DOPA), a racemic form of the antiparkinsonian drug Levodopa and a biosynthetic precursor of melanins, was developed. The synthesis involves 3 stages, and an overall yield of the target product 59%, which is higher than in the previously reported syntheses. At the first stage, 3,4-dimethoxybenzaldehyde was introduced in condensation reaction with benzoylglycine to obtain azlactone with 83% yield. The subsequent hydrolysis and reduction by Raney alloy in an alkaline medium, carried out in one stage, gave 3-(3,4-dimethoxyphenyl)-2-(benzoylamino)propanoic acid with 90% yield. Further, the removal of the protective groups with hydrobromic acid followed by treatment with aqueous ammonia resulted in the formation of 2-amino-3-(3,4-dihydroxyphenyl)propanoic acid with 80% yield. The structure of all the synthesized compounds was confirmed by NMR and IR spectroscopy and elemental analysis, as well as by the X-ray diffraction analysis of (Z)-2-benzamido-3-(3,4-dimethoxyphenyl)acrylic acid, an intermediate in the synthesis of DOPA.