γ-Turn Mimicry with Benzodiazepinones and Pyrrolobenzodiazepinones Synthesized from a Common Amino Ketone Intermediate.

ABSTRACT

To investigate diazepinone analogues as γ-turn mimics, seven 1,4-benzodiazepin-2-ones 6 and fourteen pyrrolo[1,2-d][1,4]benzodiazepin-6-ones 4 and 5 were synthesized from 1-(2-aminophenyl)pent-4-en-1-one (7). Acylation of aniline 7 with N-Boc-amino acids, olefin oxidation, Boc removal, and intramolecular Paal-Knorr condensation gave 4 and 5. Alternatively, Boc removal prior to oxidation gave benzodiazepinones 6, which were converted to 4 by ozonolysis and cyclization. Comparison of dihedral angle values for the amino acid component from X-ray analyses of 4g, 5f, and 6f and related diazepinones has catalogued the manner by which ring substituents affect the component's ability to mimic the central residues of γ-turns.