Cephalostatin support studies. Part 19. Outer-ring stereochemical modulation of cytotoxicity in cephalostatins

[GRAPHICS] 20- and 25'-epimers of cephalostatin 7, prepared by directed unsymmetrical pyrazine synthesis, address outer-ring topographical and stability questions and intimate an oxacarbenium ion rationale for the role in bioactivity of the spiroketal (E/F, E'/F') rings of this class of antitumor agents.