New cyclopenta[a]naphthalene derivatives: Synthesis of 2-(carbamylmethyl)-8-hydroxy-3H-cyclopenta[a]naphthalene as a possible deoxyribonucleic acid binding agent

Article abstract of DOI:10.1021/jm00179a008

8-Methoxy-1-oxo-2,3-dihydro-1H-cyclopental[a]naphthalene (4) was converted to the oxalyl derivative (7) by treatment with diethyl oxalate in the presence of sodium ethoxide. Compound 7 in the form of the sodium salt was alkylated with ethyl bromoacetate in DMF to 2-(carbethoxymethyl)-8-methoxy-1-oxo-2,3-dihydro-1H-cyclopenta[a]naphthalene (8). Treatment of 8 with methanolic ammonia yielded the corresponding amide (9). Dealkylation of 8 with 48% HBr and subsequent esterification gave compound 10. Ammonolysis of 10 led to the amide 11, which after reduction and subsequent dehydration of the reduced product afforded the desired compound, 2-(carbamylmethyl)-8-hydroxy-3H-cyclopenta[a]naphthalene (2). Compound 2 was found to be mildly growth inhibitory to L1210 and CCRF-CEM leukemic cells in culture. From thermal transition temperature studies, compound 2 was found to bind to calf thymus DNA and the poly(deoxyribonucleotides), e.g., poly(dG)-poly(dC), poly(dG-dC), poly(dA)-poly(dT), and poly (dA-dT).