A simple transformation of the eight-carbon side chain of a natural spirostan sapogenin into the cephalostatin north 1 spiroketal moiety is described. This methodology, based on an intramolecular hydrogen abstraction reaction promoted by alkoxy radicals, permits the synthesis of C-22 and C-25 stereoisomers of the dioxaspiro[4.4]nonane cephalostatin ring system. The acid-catalyzed isomerization of the spirocenter in the different isomers is studied. [reaction: see text]