Oxidation Chemistry of 1,2-Dehydro-N-acetyldopamines: Direct Evidence for the Formation of 1,2-Dehydro-N-acetyldopamine Quinone

Two-electron oxidation of catecholamines either by phenol oxidase or by chemical oxidants such as sodium periodate produces their corresponding o-quinones as observable products. But, in the case of 1,2-dehydro-N-acetyldopamine, an important insect cuticular sclerotizing precursor, phenol oxidase catalyzed oxidation has been reported to generate a quinone methide analog as a transient, but first observable product. [Sugumaran, M., Semensi, V., Kalyanaraman, B., Bruce, J. M., and Land, E. J. (1992) J. Biol. Chem. 267, 10355–10361]. The corresponding quinone has escaped detection until now. However, in this paper, for the first time, we present direct evidence for the formation of dehydro-N-acetyldopamine quinone and show that it can readily be produced from the tautomeric quinone methide imine amide during the chemical oxidation of dehydro-N-acetyldopamine under acidic conditions. This situation is in sharp contrast to other known alkyl-substituted catechol oxidations, where quinone is the first observable product and quinone methide is the subsequently generated product. Dehydro-N-acetyldopamine quinone thus formed is also highly unstable. Semiempirical molecular orbital calculation also indicates that quinone methide imine amide is more stable than the quinone. Chemical considerations indicate that the quinone methide tautomer, and not the dehydro-N-acetyldopamine quinone, is responsible for crosslinking the structural proteins and chitin polymer in the insect cuticle. Therefore, the quinone methide tautomer, and not the quinone, is the key reactive intermediate aiding the hardening of insect cuticle.