Approach to the total synthesis of new Pseudomonas antifungal metabolites containing a 2-pyrroline-5-carboxyl moiety

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 phytopathogenic fungi. In 2011 Wen Li & co-workers isolated a novel type of secondary metabolites produced by Pseudomonas putida RW10S1 to promote its own swarming and biofilm formation, and to selectively inhibit many other Pseudomonas, including multidrug resistant clinical isolates of the opportunistic human pathogen Pseudomonas aeruginosa (IC50 = 1.75 µM). The amphipathic nature of these antibiotics, their role in bacterial quorum sensing and the unprecedented structural features, containing a unique 2-pyrroline-5-carboxyl moiety, enticed us to develop a synthetic sequence to this nucleus, which could be adopted for the construction of variously substituted compounds with the same skeleton. The proposed route is centred on the use of L-pyroglutamic acid as a chiral synthon for the synthesis of 2-pyrroline-5-carboxyl moiety. Key step of the sequence is the reduction of N-protected pyroglutamate by Super-Hydride, followed by dehydratation of the resulting lactamol.