Total Synthesis of (±)-Distomadines A and B

The
total synthesis of distomadines A and B, two structurally unique
tetracyclic quinolines, is described. The route features a three-step
process to access the pyranoquinoline butenolide rings via a Suzuki
cross coupling of a 5-bromo-4-methoxycarbonylmethoxyquinoline with
a vinyl boronate, followed by an α-ketohydroxylation and double
cyclization by intramolecular aldol condensation and lactonization.
Subsequent manipulation of the side chain to introduce the guanidine
fragment completed the synthesis of distomadine B, whereas the distomadine
A congener resulted from decarboxylation of a late-stage intermediate.