Selective Synthesis of Divergolide I

Divergolide
I (1) is a naphthoquinone ansamycin that
exhibits broad antibacterial activity. Its tetracyclic ring system
is believed to be biosynthetically assembled via ring contraction
of a macrocyclic precursor (proto-divergolide) that
is both a macrolactone and a macrolactam. We here report a convergent
and enantioselective synthesis that delivers the target molecule in
less than 20 linear steps. Our work establishes the absolute configuration
of divergolide I, confirms its relative configuration, and demonstrates
that the biomimetic cyclization of a proto-divergolide
can be surprisingly selective.