Role of the enamide linkage of nucleoside antibiotic mureidomycin A: synthesis and reactivity of enamide-containing analogues

The reactivity of an unusual enamide functional group in the nucleoside ant ibiotic mureidomycin A (MRD A) has been investigated by synthesis of enamid e-containing analogues. Enamides based on 2-methoxyethylamine and tetrahydr ofurfurylamine were found to be unstable and reactive, whereas a uridine-ba sed analogue showed high stability and low reactivity. Samples of mureidomy cin A and the uridine-based analogue were found to be stable towards acid-c atalysed tautomerisation and nucleophilic attack. The lack of reactivity an d lack of enzyme inhibition shown by the uridine-based analogue are not con sistent with the involvement of the enamide group in slow-binding inhibitio n of translocase I.