Synthesis of perhydro-2(1H)-quinoxalinones and perhydropyrrolo[1,2-a]quinoxalin-4(5H)-one derivatives

The novel trans-bicyclic-perhydro-2(1H)-quinoxalinones 4, 6 and 7 and the tricyclic-perhydropyrrolo[1,2-a]-quinoxalin-4(5H)-one derivatives 8 and 9 are prepared via a ring opening and spontaneous ring closing reaction of the aziridines 2 and 3 with the α-amino acids glycine, L-alanine, L-proline and L-phenylalanine. This methodology was used to prepare 5 and 10 which are novel rigid analogues of the kappa opioid compound 1. Treatment of aziridine 3 with methyl carbamate gave the cyclic urea 11.