First Total Synthesis of Pestasulfamides A and B Through Iminoketene Dimerization of Anthranilic Acid in One-Pot Manner

Pestasulfamides A and B are phenylbenzene-sulfonamides with an eight-membered dilactam, produced by mangrove endophytic fungus <i>Pestalotiopsis</i> sp. HNY36-1D. In bioassay, pestasulfamide A (<b>1</b>) exhibited potent anti-acetylcholine esterase (AChE) activities with an IC50 value of 11.94 μM, offering new pharmacophores with relevance to anti-Alzheimer's disease drug discovery. Although the dimerization reaction of anthranilic acid derivatives forges an dibenzodiazocin-2,6-dione framework, the application of the dimerization to total synthesis of pestasulfamides A (<b>1</b>) and B (<b>2</b>) has not yet been realized. Herein, the first total synthesis of pestasulfamides A and B was achieved through one-pot protocol. The key step features a sulfonylation-induced iminoketene dimerization of anthranilic acid in a pyridine/THF system.