An Unusual Decarboxylative Maillard Reaction between l-DOPA and d-Glucose under Biomimetic Conditions: Factors Governing Competition with Pictet−Spengler Condensation

Abstract

In 0.1 M phosphate buffer at pH 7.4 and 37 °C, the tyrosine metabolite l-3,4-dihydroxyphenylalanine (l-DOPA) reacts smoothly with d-glucose to afford, besides diastereoisomeric tetrahydroisoquinolines 1 and 2 by Pictet−Spengler condensation, a main product shown to be the unexpected decarboxylated Amadori compound N-(1-deoxy-d-fructos-1-yl)-dopamine (3). Under similar conditions, dopamine gave only tetrahydroisoquinoline products 4 and 5, whereas l-tyrosine gave exclusively the typical Amadori compound 6. Fe³⁺ and Cu²⁺ ions, which accumulate in relatively high levels in parkinsonian substantia nigra, both inhibited the formation of 3. Cu²⁺ ions also inhibited the formation of 1 and 2 to a similar degree, whereas Fe³⁺ ions increased the yields of 1 and 2. Apparently, the formation of 3 would not be compatible with a simple decarboxylation of the initial Schiff base adduct, but would rather involve the decarboxylative decomposition of a putative oxazolidine-5-one intermediate assisted by the catechol ring. These results report the first decarboxylative Maillard reaction between an amino acid and a carbohydrate under biomimetic conditions and highlight the critical role of transition metal ions in the competition with Pictet−Spengler condensation.