Studies on the fluorophore forming reactions of various catecholamines and tetrahydroisoquinolines with glyoxylic acid

Abstract

Strongly fluorescent 2-carboxymethyl-3,4-dihydro-7-hydroxyisoquinolin-6-ones are formed in high yields when catecholamines are reacted with glyoxylic acid. Formation of the fluorophores has been found to take place in two steps; i. e. via virtually non-fluorescent tetrahydroisoquinoline-1-carboxylic acids, which react to give the fluorophores in a subsequent, rapid reaction with glyoxylic acid. The rates of reaction (pseudo first-order) with glyoxylic acid for 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid, and 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline-3- carboxylic acid show that introduction of a carboxyl group at either C-1 or C-3 in a tetrahydroisoquinoline highly facilitates the reaction with glyoxylic acid. This behaviour is discussed in terms of a mechanism involving both intramolecular acid catalysis by the C-1 or C-3-carboxyl groups during dehydration of the carbinolamine intermediate, and facilitation of the prototropic shifts of the resulting Schiff's base by decarboxylation.