苯甲醛上苄基.pdf

FULL PAPER 6-Spiro-1,4-diazepane-2,5-diones by Head-to-Tail N1/C2 Amide Bond Formation Leon W. A. Van Berkom,[a] René de Gelder,[b] and Hans W. Scheeren*[a] Keywords: Spiroheterocycles / Cyclisation / Cyclic dipeptides / Diazepane The synthesis of a series of 6-spiro-1,4-diazepane-2,5-diones C5 amide bond proved unsuccessful, ring closure of the N1/ containing an arylpropylamide moiety via head-to-tail cyclis- C2 amide bond was more viable. Furthermore, it was discov- ation of a terminal amine and a terminal carboxylate ester is ered that incorporation of a N,N-disubstituted amide bond in described. To induce ring closure of the dipeptide precursor, the peptide sequence was essential for cyclisation to occur. both lactamisation of the N4/C5 amide bond and N1/C2 am- (© Wiley-VCH Verlag GmbH Co. KGaA, 69451 Weinheim, ide bond were investigated. Whereas ring closure of the N4/ Germany, 2005) Introduction azepane-2,5-diones I were envisioned to arise from the lin- ear dipeptides II or III via lactamisation of the N4/C5 or The exploration of privileged structures in drug discov- the N1/C2 amide bond (pathways A and B, Figure 1). In ery has gained significant popularity and relevance in recent turn, precursor II and III can be obtained from the cyclic [1] years. An important example of these privileged struc- masked β-amino ester IV which can be prepared from 3- tures, the 1,4-benzodiazepine-2,5-diones, have been re- aryl-2-cyanoprop-2-enoa