SYNTHESIS AND EFFECT ON FREE-RADICAL PROCESSES OF SOME SUBSTITUTED MORPHOLINE DERIVATIVES WITH POTENTIAL BIOLOGIC ACTIVITY

Since a number of 2-hydroxy (alkoxy)-2-phenyl-4 (5,6)(tri) alkyl-morph olines presented antioxidant and interesting biologic activity which m ay, implicate free radical processes, some 2-hydroxy (alkoxy)-2-biphen yl-4-methyl-morpholine derivatives were prepared in an attempt to synt hesize more potent antioxidants with interesting biologic action. The 2-hydroxy-2-biphenyl-4-methyl-morpholine was prepared by reacting the N-methyl-ethanolamine with the p-phenyl-phenacylbromide, the 2-hydoxy- derivative formed after spontaneous cyclisation gave the 2-alkoxy-2-bi phenyl-4-methyl morpholines by an acid catalyzed ketal formation. The lipophilicity of the synthesized compounds was determined by the rever sed phase TLC technique as R(M) values. The synthesized 2-biphenyl sub stituted morpholines were evaluated for their antioxidant activity on hepatic microsomal lipid peroxidation and on hydroxyl radical mediated oxidation of dimethylsulfoxide. The synthesized compounds were found to posses potent antioxidant activity. A possible mechanism was propos ed for the antioxidant properties awhile lipophilicity was found not t o be an important determinant of this property.