A practical synthesis of pyoluteorin

A convenient, large‐scale synthesis of the antibiotic pyoluteorin, 2,3‐dichloro‐5‐(2′,6′‐dihydroxybenzoyl)‐pyrrole ( 1 ), is described. A key step in the synthesis involved a Friedel‐Crafts aroylation of pyrrole with 2,6‐dimethoxybenzoyl chloride ( 3 ) in methylene chloride. The desired intermediate, 2‐(2′,6′‐dimethoxybenzoyl)pyrrole ( 4 ), was obtained as the major product, along with a product of beta substitution ( 6 ). Compound 4 was converted to pyoluteroin ( 1 ) in four steps in an overall yield of 51%.