HETEROCYCLIC NONIONIC X-RAY CONTRAST AGENTS .5. A FACILE CONVERSION OF 2-TETRAHYDROFUROAMIDES INTO ALPHA-HYDROXY-DELTA-VALEROLACTAMS AND A GENERAL-SYNTHESIS OF LACTAMS CONJUGATED TO 2,4,6-TRIIODOISOPHTHALAMIDES

The synthesis of 2,4,6-triiodoisophthalamides substituted by a lactam moiety is described. A tandem ring opening-ring closure methodology co nsisting of a regiospecific ether cleavage of the tetrahydrofuroanilid e 14b, followed by lactamization to alpha-oxygenated anilides 15b or 1 6b, gave alpha-O-functionalized-delta-valerolactams 12b or 13b, respec tively. This approach is also compatible with the presence of ester an d carbonyl chloride functions on the triiodophenyl moiety. A general s ynthesis of lactams 34-39 was also achieved. Further chemical modifica tions led to water soluble unsubstituted-lactams (34d, 35d, 37d) and a lpha-hydroxy-lactams [42(d,e), 13(d,e) and 43d] that are of interest a s X-ray contrast agents. Copyright (C) 1996 Elsevier Science Ltd