Efficient synthesis and structural analysis of new dioxopiperazine isoquinolines

Abstract We report herein the synthesis of new dioxopiperazine isoquinolines using the Pictet–Spengler cyclisation. Our synthetic strategy for the preparation of two new compounds ( 5 , 6 ), with a tetrahydro-6 H -pyrazino[1,2- b ]isoquinoline-1,4-dione moiety was developed in only four steps. To understand better the crucial step of the synthesis reported here, theoretical calculations using semiempirical (PM3), ab initio and DFT computations were carried out on a reduced system model. The structure of chlorohydrate water solvate of tetrahydro (2-piperidinylethyl)-6 H -pyrazino [1,2- b ]isoquinoline-1,4-dione ( 6 ·HCl·2H 2 O ) was determined by X-ray diffraction. Theoretical calculations (RHF/3-21G and RB3LYP/6-31G(d)) were also performed for compound 6 neutralised with a chloride ion.