Oxa–diketopiperazines: Access and Conformational Analysis of Potential Turn Inducers

Abstract

An improvement of the 1,2,5-oxadiazine-3,6-diones (Oxd) synthesis and reactivity is described in this paper. The methodology has been successfully applied to produce a library of this poorly studied scaffold, which can be considered as an oxa-diketopiperazine (oxa-DKP). Significantly, the first crystal structures of oxa-DKP were obtained and compared to the diketopiperazine ring. Finally, a straightforward procedure concerning the coupling of various amino acids with oxa-DKP heterocycles to afford original peptidomimetics was reported. The conformational analysis realized on di- and tripeptide analogs revealed that the oxa-DKP skeleton exhibited remarkable β-turn inducer properties.