Rapid Cascade Synthesis of Poly-Heterocyclic Architectures from Indigo

The
base-induced propargylation of the dye indigo results in the
rapid and unprecedented one-pot synthesis of highly functionalized
representatives of the pyrazino­[1,2-a:4,3-a′]­diindole, pyrido­[1,2-a:3,4-b′]­diindole and benzo­[b]­indolo­[1,2-h]­naphthyridine heterocyclic systems, with the last two
reflecting the core skeleton of the anticancer/antiplasmodial marine
natural products fascaplysin and homofascaplysins and a ring B-homologue,
respectively. The polycyclic compounds 6–8, whose structures were confirmed through single-crystal
X-ray crystallographic analysis, arise from sequential inter/intramolecular
substitution–addition reactions, and in some cases, ring rearrangement
reactions. Preliminary studies on controlling the reaction path selectivity,
and the potential reaction mechanisms, are also described. Initial
biological activity studies with these new heterocyclic derivatives
indicated promising in vitro antiplasmodial activity as well as good
anticancer activity. The chemistry described is new for the indigo
moiety and cascade reactions from this readily available and cheap
starting material should be more broadly applicable in the synthesis
of additional new heterocyclic systems difficult to access by other
means.