Approach to synthesis of the natural compound Leopolic Acid A

Leopolic Acid A (1) has recently been isolated from a terrestrial-derived Streptomyces sp isolated from the rhizosphere of the plant Juniperus excels collected from Ukraine.1 It possesses a rare ureido dipeptide Phe-CO-Val attached to 5-dihydro-3-hydroxy-pyrrole-2-one ring. Ureido-peptides with varying number of amino acids have been previously isolated from actinomycetes ann show intesting biological activities. Noteworthy examples include the microbial alkaline protease inhibitors, (MAPI)-a and b, GE20372 factor A and B, as HIV-1 protease inhibitors, and the pacidamycins, exhibiting anti-Pseudomonas aeruginosa The unprecedented structural features of Leopolic acid, consisting of an aliphatic side chain attached to the novelpyrrole-2-one residue connected to the ureido dipeptide, prompted us to develop a synthetic strategy of this naturally occurring compound. The proposed methodology is centred on the condensation of .the 4-substituted 3-hydroxy-1,5-dihydropyrrol-2-one (2) and the ureido dipeptide moiety (3).