Enantioselective Total Synthesis of the Putative Biosynthetic Intermediate Ambruticin J

The family of anti-fungal natural products known as the ambruticins are structurally distinguished by a pair of pyran rings adorning a divinylcyclopropane core. Previous characterization of their biosynthesis, including the expression of a genetically modified producing organism, revealed that the polyketide synthase pathway proceeds via a diol intermediate, known as ambruticin J. Herein, we report the first enantioselective total synthesis of the putative PKS product, ambruticin J, according to a triply convergent synthetic route featuring a Suzuki-Miyaura cross-coupling and a Julia-Kocienski olefination for fragment assembly. This synthesis takes advantage of synthetic methodology previously developed by our laboratory for the stereoselective generation of the trisubstituted cyclopropyl linchpin.

Automated summary

The ambruticins, a family of anti-fungal natural products, are characterized by a divinylcyclopropane core adorned with a pair of pyran rings. The biosynthesis of these compounds involves a polyketide synthase pathway, with a diol intermediate known as ambruticin J. Researchers have reported the first enantioselective total synthesis of ambruticin J using a triply convergent synthetic route.