“…The ability of soraphen A to inhibit ACC and modulate the biosynthesis and metabolism of fatty acids evokes numerous therapeutic opportunities across diverse human diseases. , Indeed, based on the biology surrounding soraphen A, firsocostat, a synthetic ACC inhibitor, was designed and has advanced to phase II clinical trials for treatment of non-alcoholic steatohepatitis . Despite its availability via fermentation, clinical candidates based on soraphen A itself have proven elusive due to their poor pharmacokinetic properties and the relatively narrow range of structural analogues accessible via semi-synthesis. , After 30 years since its discovery, and despite numerous reports of substructure syntheses, efforts toward the total synthesis of soraphen A have resulted in only three total syntheses (two by Giese , and one by Trost), which are 25, 36, and 25 steps in length (longest linear sequence, or LLS). The de novo syntheses of C11-desmethoxy-soraphen A and so-called “paleo-soraphens” , also have been described.…”