Progress Towards the Total Synthesis of the Antimicrobial Pigment Violacein and its Analogs

Violacein is a purple bacterial pigment produced by several strains of Gram-negative bacteria species including Chromobacterium violaceum and Janthinobacterium lividum. A member of bisindole alkaloid natural product family, violacein is biosynthesized from two-molecules of L-tryptophan mediated by an operon consisting of five genes. It has demonstrated promising anti-microbial properties including anti-bacterial, anti-fungal, anti-viral and anti-tumoral activities. Despite the extensive research investigating biosynthesis of violacein for its potential biological activities, the synthesis of violacein by chemical means has not been widely explored. Previous reports on chemical synthesis of violacein involved step-wise addition of two indole subunits to the central 5-membered pyrrolidone ring. These methodologies had some disadvantages including the need for preparation of specific starting materials and low yields in each step of the synthesis. Our work in this area has focused on an efficient preparation of the violacein synthetic scaffold based on a new three-component pyrrolidone cyclization. We are investigating the mechanistic details of this reaction and optimizing the solvent and temperature conditions while working towards the total synthesis of violacein and its analogs