Compounds Related to Podophyllotoxin. XII. Podophyllotoxone, Picropodophyllone and Dehydropodophyllotoxin

Manganese dioxide converts podophyllotoxin and picropodophyllin to the corresponding ketones, podophyllotoxone and picropodophyllone. The ketones with sodium borohydride give the same product, a hydroxy acid. In contrast, zinc borohydride regenerates podophyllotoxin from podophyllotoxone, and regenerates picropodophyllin from picropodophyllone. Both podophyllotoxone and picropodophyllone on treatment with selenium dioxide give the naphthol, dehydropodophyllotoxin, identical with the material isolated by Kofod and Jørgensen from podophyllin resin. The ultraviolet and infrared absorption data, the fact that manganese dioxide readily oxidizes podophyllotoxin and picropodophyllin to the ketones, and the fact that an oxidative process converts the ketones to a naphthol all point to the α-tetralol structures of podophyllotoxin and picropodophyllin. Accordingly, the present work provides independent evidence for the presence of a secondary hydroxyl group, and, when the known carbon skeleton is taken into account, provides independent evidence for the position of the hydroxyl group. Methylmagnesium bromide adds to podophyllotoxone to give two stereoisomeric methylpodophyllotoxins. Phenylhydrazine reacts with podophyllotoxone to give a pyrazoline acid instead of the phenylhydrazone.