Synthesis of pentenoic acid analogs as potential anti-influenza agents

摘要

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