SYNTHESIS OF 4-AMINO SUBSTITUTED AND 4-UNSUBSTITUTED 1,10-PHENANTHROLINE-3-CARBOXYLIC ACID-DERIVATIVES AS POTENTIAL DNA CLEAVAGE REAGENTS

The synthesis of several new 4-amino substituted and 4-unsubstituted 1 ,10-phenanthroline-3-carboxylic acid derivatives are reported. The 4-a mino derivatives (5,6,7) were prepared from 1,4-dihyro-4-oxo-1,10-phen anthroline-3-carboxylic acid (2) via aromatization and 4-chlorination, followed by nucleophilic substitution at C4 by the appropiate alkyl a mine. Tile 4-unsubstituted derivatives (10,11,12) were prepared by aro matization and 4-chlorination of ethyl 4-dihydro-1-oxo-1,10-phenanthro line-3-carboxylate. The substituent at C4 was removed by conversion to the 4-tosyl hydrazide, followed by base-catalysed elimination of the hydrazide group. These phenanthroline derivatives were designed as met al-ion-complex mediated DNA cleavage reagents. In both series the 3-ca rboxylic acid side chain was coupled to beta-alanine to facilitate its conjugation with DNA binding molecules.