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

Oxidation of N,N-dialkyldopamines double dagger by either dianisyltellurium oxide or tyrosinase gives 2,3-dihydro-1H-indolium-5-olates which are forme d by cyclisation of an intermediate o-quinone. The kinetics of formation an d cyclisation of the N,N-dimethyl-o-quinone have been studied using pulse r adiolysis. The indolium-5-olates do not activate met-tyrosinase and these r esults 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 intermedi ate catechol. Similar chemical and enzymatic oxidation of a higher homologu e gives an analogous 1,2,3,4-tetrahydroquinolinium-6-olate. Pulse radiolysi s 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 di methoxy iodide salts. In a preliminary investigation of potential anti-canc er pro-drugs, amide derivatives of dopamine do not cyclise when oxidised to the o-quinone but cyclisation of an N-benzoylmethyl derivative to the corr esponding betaine was observed. This betaine then appears to equilibrate wi th an N-ylide which, in contrast to the betaine, is a substrate for tyrosin ase.