Synthesis, central nervous system activity and teratogenicity of a homothalidomide.

The optical isomers of alpha-phthalimidoadipinimide (1) were synthesized by a route based on D(+)- and L(-)-amino-epsilon-caprolactam (5) as synthon. The isomers of 1 were obtained in high yields by treating D(+)- and L(-)-amino-epsilon-caprolactam (5) with N-carboethoxyphthalimide (4), followed by oxidation with benzeneseleninic anhydride (7). The teratogenic potency of both isomers of 1 was studied by the HET-(Hen's Egg Test); 1 caused distinctly lower teratogenic effects in contrast to thalidomide (2). D(-)-1 and L(+)-1 showed sedative effects with a lower activity than 2. Both are more stable in alkaline solution at the same time with a smaller tendency for racemization.