Site selective synthesis of cytotoxic 1,3,6-trisubstituted 3,6-diunsaturated (3Z,6Z)-2,5-diketopiperazines via a one-pot multicomponent method.

A one-pot multicomponent approach was established for site selective synthesis of novel 1,3,6-trisubstituted 3,6-diunsaturated ( 3Z,6Z )-2,5-diketopiperazine derivatives with high stereoselectivity. The computational studies revealed that the steric hindrances between the 2-hydrogen atoms on the aromatic rings and the carbonyl, as well as the steric repulsions between the hydrogen atoms of the CH group in the benzylidene and the CH 2 group in the N -alkylative part might be responsible for the Z / E selectivity. Compound ( 3Z,6Z )- 3h (IC 50 =11 nM) has a close activity to the positive compound plinabulin (IC 50 =15 nM) against the cancer cell line HL60. [ABSTRACT FROM AUTHOR]