Purinylhydantoins. Facile conversion of the naturally occurring N-(purin-6-ylcarbamoyl)-L-amino acids into 3-pruin-6-ylhydantoins and 3-cyclohexyl-1-(purin-6-ylcarbamoyl)hydantoins.
The naturally occurring N-(purin-6-ylcarbamoyl)-L-threonine (PCT, 1b), N-(purin-6-ylcarbamoyl)glycine (PCG, 1a), and some of their analogs were converted into novel purine derivatives, the purinylhydantoins. The PCT and PCG underwent intramolecular cyclization in the presence of N,N-dicyclohexylcarbodiimide (CDD) to give the 3-purin-6-ylhydantoins (2a-c). The same hydantoins were also obtained when the PCT and PCG were allowed to react through the mixed anhydride formed from cyclohexyl isocyanate or ethyl chloroformate. 1,3-Dicyclohexyl-1-(N-(purin-6-ylcarbamoyl)aminoacyl)ureas 3a and 3c, by-products obtained from the DCC reaction, were rapidly converted in aqueous NaOH to another type of purinylhydantoins, the 3-cyclohexyl-1-(purin-6-ylcarbamoyl)hydantoins 4a and 4b. Compound 4a when heated in base underwent hydrolysis of the hydantoin ring giving biuret N-(cyclohexylcarbamoyl)-N-(purin-6-ylcarbamoyl)glycine (5a) and N-(purin-6-ylcarbamoyl)glycine cyclohexylamide (6a). The characterization of these hydantoins was carried out by uv, nmr, and mass spectrometry. The 3-purin-6-ylhydantoins and 3-cyclohexyl-1-(purin-6-ylcarbamoyl)hydantoins showed growth inhibitory activity in the cultured leukemic cells, while the parent amino acid compounds were inactive.
D000596:Amino Acids; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000627:therapeutic use; D002219:Carbamates / Q000138:chemical synthesis / Q000627:therapeutic use; D002460:Cell Line; D006827:Hydantoins / Q000138:chemical synthesis* / Q000627:therapeutic use; D007939:Leukemia L1210 / Q000188:drug therapy; D015470:Leukemia, Myeloid, Acute; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D011687:Purines / Q000138:chemical synthesis* / Q000627:therapeutic use; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
D000596:Amino Acids; D000970:Antineoplastic Agents; D002219:Carbamates; D006827:Hydantoins; D011687:Purines