First Total Synthesis of (±)‐Anthogorgiene A, Marine‐Derived Guaiazulene‐Based Secondary Metabolite

The study presents the first total synthesis of the sesquiterpene natural product (±)‐Anthogorgiene A. Starting from commercially available 4‐bromo‐2‐methylbenzoic acid, the synthesis proceeds through a five‐step sequence to construct a rearranged guaiazulene‐based carbon framework featuring a β‐methylindanone core. The key steps include an optimized esterification to generate a suitably substituted benzoate ester, followed by a one‐pot polyphosphoric acid (PPA)‐mediated fragmentation, a Friedel–Crafts acylation, and a subsequent Nazarov cyclization. This sequence enables the efficient and regioselective formation of a fused bicyclic ring system, culminating in the exclusive introduction of a β‐methyl group on the 1‐indanone scaffold. Overall, the approach provides a concise and effective route to access the complex architecture of (±)‐Anthogorgiene A.