Synthesis and structure of novel ( S)-1,6-dialkylpiperazine-2,5-diones and (3 S,6 S)-1,3,6-trialkylpiperazine-2,5-diones

Abstract

Eleven ( S)-1,6-dialkylpiperazine-2,5-diones and five (3 S,6 S)-1,3,6-trialkylpiperazine-2,5-diones were prepared in three steps from the corresponding ( S)-α-amino acid esters comprising of reductive N-alkylation, N-acylation and cyclisation. The synthesis of ( S)-1,6-dialkylpiperazine-2,5-diones has a broad scope allowing preparation of diketopiperazines with primary and secondary alkyl groups at N(1), while the synthesis of (3 S,6 S)-1,3,6-trialkylpiperazine-2,5-diones is limited to compounds with primary alkyl groups at N(1). Reductive alkylation of amino acid ester hydrochlorides by catalytic hydrogenation in the presence of a carbonyl compound proved to be a simple, efficient and general method for the preparation of stable (storable) α-alkylamino acid ester hydrochlorides. The structures of the novel compounds were determined by NMR and X-ray diffraction.