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

Abstract

The reactivity of an unusual enamide functional group in the nucleoside antibiotic mureidomycin A (MRD A) has been investigated by synthesis of enamide-containing analogues. Enamides based on 2-methoxyethylamine and tetrahydrofurfurylamine were found to be unstable and reactive, whereas a uridine-based analogue showed high stability and low reactivity. Samples of mureidomycin A and the uridine-based analogue were found to be stable towards acid-catalysed tautomerisation and nucleophilic attack. The lack of reactivity and lack of enzyme inhibition shown by the uridine-based analogue are not consistent with the involvement of the enamide group in slow-binding inhibition of translocase I.