Approach towards the total synthesis of salicyloyl enamide Containing Pseudomonas antifungal metabolites

Recent studies on the bio-control activity of plant-associated Pseudomonas have revealed their ability to produce a series of antagonistic molecules to compete with other microorganisms, in particular the phytopathogenic fungi. In 2011 Wen Li & co-workers isolated a novel type of secondary metabolites produced by P. putida RW10S1 to promote its own swarming motility and biofilm formation. It also selectively inhibit many other Pseudomonas, including multidrug resistant clinical isolates of the opportunistic human pathogen P.aeruginosa (IC50 = 1.75 µM). The antibiotics are amphipathic in nature and manifest key role in bacterial quorum sensing. The unprecedented structural features, containing a unique salicyloyl enamide moiety, enticed us to develop a synthetic sequence to this nucleus. The synthesis could be adopted for the construction of variously substituted analogues with the same skeleton. The proposed route is centred on the use of L-pyroglutamic acid as a chiral synthon for the synthesis of the enamide moiety. Key step of the sequence involves the reductive elimination of N-protected pyroglutamate.