Synthesis of C11-Desmethoxy Soraphen A1α: A Natural Product Analogue That Inhibits Acetyl-CoA Carboxylase

A synthesis of C11-desmethoxy soraphen A 1α is described that proceeds in just 14 steps from readily available starting materials. This natural product analog was identified as a target of interest in a program aimed at identifying novel natural product-inspired inhibitors of acetyl-CoA carboxylase (ACC) as potential anticancer therapeutics. While describing the most efficient synthesis of a soraphen A 1α analog (total syntheses of the natural product have been reported that proceed in 25 to ≥40 linear steps), we also present data supporting the conclusion that C11-heteroatom functionality is a beneficial but unnecessary structural characteristic of soraphen A 1α analogs for inhibiting ACC.