Novel naphthoquinonyl derivatives: Potential structural components for the synthesis of cytotoxic peptides

Syntheses and physicochemical properties are described of several novel naphthoquinonyl amino acid derivatives, which are potential components in cytotoxic peptide conjugates. These compounds include N^ε- and N^α-naphthoquinonyl derivatives of lysine as well as N-naphthoquinonyl-carboxylic derivatives. The former class of compounds can be employed as building blocks in a stepwise peptide synthesis, whereas the latter two are adequate for post-peptide chain-assembly modifications. The ability of the naphthoquinonyl derivatives to produce semiquinone radicals and hydroxyl radicals (^•OH), using chemical (i.e. NaBH₄) and enzymatic (i.e. NADPH-cytochrome P-450 reductase) routes, respectively, was evaluated employing electron spin resonance spectroscopy.