Multiple-spiro/fused-heterocyclic frameworks containing indazolone are structurally
unique and represent a class of potentially dominant skeletons. In this work, we successfully
fulfilled Rh(III)-catalyst mediated substrate- and pH- controlled strategies to construct
four novel types of complicated penta-spiro/fused-heterocyclic frameworks via C-H
activation/[4+1] and [4+2] annulation cascades. This method had mild reaction conditions,
a broad scope of substrates, moderate to good yields, and valuable applications, which
could realize for the first time the generation of the novel di-spiro-heterocyclic
and multiple fused-heterocyclic products with unique structures. More importantly,
novel spiro[cyclohexane-indazolo[1,2-a]indazole] scaffold constructed by this method
exhibited potent antitumor activity against a variety of refractory solid tumors and
hematological malignancies in vitro. Overall, our work provided new insights into
the construction of complex and diverse multiple spiro/fused-heterocyclic systems
and offered novel valuable lead compounds for the discovery of antitumor drugs.
