Electrochemistry of podophyllotoxin derivatives: Part II. Oxidation of teniposide and some epipodophyllotoxin derivatives

Abstract

Oxidation of the anions of teniposide (I) and its aglycone (III) occurs over the pH range from 3 to 12 in two one-electron waves. The loss of the first electron yields a radical, the second a phenoxenium ion. The latter is converted by nucleophilic attack involving hydroxide ions into an ortho-quinone. In the cis-hydroxy acids derived from teniposide (IIa) and etoposide (IIb), the oxidation occurs at pH < 9.5 in a single two-electron step. This difference in behaviour is attributed to a facilitated oxidation of the radical formed in the first electron transfer of the open chain compounds. The primary products of the two-electron oxidation of the hydroxy acids IIa and IIb undergo chemical transformations which do not involve the formation of an ortho-quinone. The difference in reactivity of the product of the one-electron oxidation between the lactones (I, III) and the corresponding hydroxy acids (IIa, IIb) results in the two-electron oxidation of hydroxy acids in the physiological pH range, and in the formation of a relatively stable radical in solutions of the lactones. The absence of a stable radical as well as the impossibility of an ortho-quinone in solutions of the hydroxy acids may be responsible for the smaller antineoplastic activities of these open chain compounds when compared to the corresponding lactones.