Heterocyclic nonionic X-ray contrast agents V: A facile conversion of 2-tetrahydrofuroamides into α-hydroxy-δ-valerolactams and a general synthesis of lactams conjugated to 2,4,6-triiodoisophthalamides

Abstract The synthesis of 2,4,6-triiodoisophthalamides substituted by a lactam moiety is described. A tandem ring opening-ring closure methodology consisting of a regiospecific ether cleavage of the tetrahydrofuroanilide 14b , followed by lactamization to α-oxygenated anilides 15b or 16b , gave α-O-functionalized-δ-valerolactams 12b or 13b , respectively. This approach is also compatible with the presence of ester and carbonyl chloride functions on the triiodophenyl moiety. A general synthesis of lactams 34–39 was also achieved. Further chemical modifications led to water soluble unsubstituted-lactams ( 34d, 35d, 37d ) and α-hydroxy-lactams [ 42(d,e), 13(d,e) and 43 ] that are of interest as X-ray contrast agents.