Synthesis of pentenoic acid analogs as potential anti-influenza agents

The synthesis of (2Z,4RS)-5-acetamido-4-guanidino-2-benzamidopent-2-enoic acid (sodium salt) 5 is reported. Wittig-Horner olefination of diamino protected propionaldehyde 8 with phosphonoglycine trimethyl ester 11 provided (Z)-olefin methyl ester 12. The methyl ester was converted to allyl ester 15 by initial hydrolysis with lithium hydroxide followed by reaction with allyl bromide. Target compound 5 was prepared from allyl ester 15 by initial formation of bis(Boc)guanidino ester 16 followed by treatment with tetrakis(triphenylphosphine)palladium(0). The product was evaluated for activity against influenza neuraminidase and was found to be weakly active.