Solid-Phase Synthesis of Hybrid 2,5-Diketopiperazines Using Acylhydrazide, Carbazate, Semicarbazide, Amino Acid, and Primary Amine Submonomers

• DOI: 10.1021/acs.joc.9b02083
• Publication Date: 2020-01-31T09:20:27Z
• Authors: Abdur Rahim; Biswajit Sahariah; Kalpita Baruah; Jugal Kishore Rai...; Bani Kanta Sarma
• Keywords: 01 natural sciences; 0104 chemical sciences

We report the solid-phase synthesis of N,N'-di(acylamino)-2,5-diketopiperazine, an acylhydrazide-based conformationally rigid 2,5-DKP scaffold having exocyclic N-N bonds. We also show that different combinations of acylhydrazides, carbazates, semicarbazides, amino acids, and primary amines can be used to synthesize a highly diverse collection of hybrid DKP molecules via the solid-phase submonomer synthesis route. Finally, we show incorporation of a methyl substituent in one of the carbon atoms of the DKP ring to generate chiral daa- and hybrid-DKPs without compromising the synthetic efficiency.