Synthesis of potential antimalarials

Abstract
A series of quinoline derivatives containing a 2‐thienyl ring in the 2‐position and CO2H, CH2OH, CHO, CH(OH)CN, CH(OH)CO2H, CO2C2H5, COCH[N(C2H5)2]CO2C2H5, COCH2N(C2H5)2, COCH3, magnified image substituents in the 4‐position was synthesized. Both intermediate and target compounds were tested for antimalarial activity. A second series with a 5‐bromo‐2‐thienyl group in the 2‐position and CHOHCH2N(C2H5)2, CHOHCH2N(CH2)6, and CHOHCH2N(CH2C6H5)2substituents in the 4‐position was also prepared, it was found that, although these quinoline methanols were moderately active antimalarials, they exhibited a high degree of phototoxicity. A third series of compounds with 2‐alkyl substituents (methyl,t‐butyl) was also synthesized, and these were found to combine a modest degree of antimalarial activity with low phototoxicity. Several novel synthetic routes to the above compounds were developed and are detailed.