Oxidative cyclisation of N,N-dialkylcatechol amines to heterocyclic betaines via o-quinones: synthetic, pulse radiolytic and enzyme studies

Abstract

Oxidation of N,N-dialkyldopamines by either dianisyltellurium oxide or tyrosinase gives 2,3-dihydro-1H-indolium-5-olates which are formed by cyclisation of an intermediate o-quinone. The kinetics of formation and cyclisation of the N,N-dimethyl-o-quinone have been studied using pulse radiolysis. The indolium-5-olates do not activate met-tyrosinase and these results support a mechanism of tyrosinase oxidation of phenols to o-quinones in which the o-quinone is formed in a single step and not via an intermediate catechol. Similar chemical and enzymatic oxidation of a higher homologue gives an analogous 1,2,3,4-tetrahydroquinolinium-6-olate. Pulse radiolysis studies show that this product is formed via a spiro intermediate and not by direct cyclisation to form the six-membered quinolinium ring. The novel betaines described have been fully characterised and converted to their dimethoxy iodide salts. In a preliminary investigation of potential anti-cancer pro-drugs, amide derivatives of dopamine do not cyclise when oxidised to the o-quinone but cyclisation of an N-benzoylmethyl derivative to the corresponding betaine was observed. This betaine then appears to equilibrate with an N-ylide which, in contrast to the betaine, is a substrate for tyrosinase.