A General Approach to the Aza-Diketomorpholine Scaffold

Organic Letters, 2017, Volume: 19, Issue: 3, Pages: 492-495, DOI: 10.1021/acs.orglett.6b03656

M. Berthet, B. Legrand, J. Martinez, I. Parrot


A stereoconservative three-step synthesis to access to 1,2,4-oxadiazine-3,6-dione is presented. This underexplored platform could be considered as a constrained oxy-azapeptide or an aza-diketomorpholine, the methodol. being then successfully applied to produce enantiopure aza-analogs of diketomorpholine natural products. Importantly, the 1st crystal structures were obtained and compared to diketomorpholine and diketopiperazine structures. Finally, a straightforward procedure concerning the coupling of this heterocyclic scaffold with various amino acids to afford original pseudodipeptide analogs was described.