The first total synthesis of the pentacyclic phenylnaphthacenoid
type II polyketide antibiotic formicamycin H is described. A key feature
of the synthesis involves the convergent, regioselective assembly
of the tetracyclic core via ruthenium-catalyzed α-ketol-benzocyclobutenone
[4 + 2] cycloaddition. Double dehydration of the diol-containing cycloadduct
provides an achiral enone, which upon asymmetric nucleophilic epoxidation
and further manipulations delivers the penultimate tetracyclic trichloride
in enantiomerically enriched form. Subsequent chemo- and atroposelective
Suzuki cross-coupling of the tetracyclic trichloride introduces the
E-ring to complete the total synthesis. Single-crystal X-ray diffraction
analyses of two model compounds suggest that the initially assigned
stereochemistry of the axially chiral C6–C7 linkage may require
revision.