“…More recently, ACCs have become of interest to those seeking novel targeted cancer therapeutics, as several studies have established that cancer cells have an intrinsic dependence on de novo fatty acid synthesis and that inhibition of ACC, the rate-limiting step of biosynthesis, triggers apoptosis of cancer cells with little to no effect on normal cells. − While soraphen A 1α has been described as a unique tool to study altered fatty acid metabolism in cancer cells, its in vivo utility appears hampered by its poor solubility and bioavailability. , Over 30 natural product family members have been isolated from Sorangium cellulosum and numerous synthetic analogues have been prepared, yet no analogues have been discovered with activity akin to 1 . Although the natural product is readily available from fermentation (∼130 mg/L), the nature of structural changes that are easily accessible from the fully functionalized natural product are quite limited; such is often the case with natural product derivatization. − Soraphen A 1α ( 1 ) has been pursued as a target for total synthesis for ∼20 years, with two successful syntheses being reported. − Unfortunately, these accomplishments call for synthetic sequences of 25 to ≥40 steps (longest linear sequence) and define a rather substantial barrier to the use of chemical synthesis for the discovery of novel soraphen analogues that may have better properties than 1 . Here, we report a concise synthesis of C11-desmethoxy soraphen A 1α ( 2 ), a natural product analogue that was targeted in a function-oriented synthesis pursuit after analysis of the ACC2– 1 structure and an assessment of the challenges that have plagued previous syntheses of 1 .…”