The Parallel Solid-Phase Synthesis of Substituted Oxopiperazin Derivatives

Significance

Solid-phase synthesis of tetrasubstituted oxopiperazinium derivatives was demonstrated. p-Methylbenzhydrylamine (MBHA) resin-bound dipeptides 1 were protected with trityl chloride. The resin-bound protected dipeptides reacted with methyl iodide to give dimethylated products 2. The resulting 2 were deprotected with TFA followed by treatment with a variety of carboxylic acids to give triamides 3. The polymer-supported triamides 3 were reduced with BH₃×THF to afford polymer-supported triamines 4. The secondary amine was coupled with bromoacetic acid in the presence of diisopropylcarbodiimide (DIC). The resulting bromoacetyl group underwent intra­molecular cyclization to form cationic oxopiperazinium which was cleaved from the polymer supports to give an epimeric mixture of the desired tetrasubstituted-5-oxopiperazinium salts 5 (18 examples; 82-95% purity).