An efficient new way to access two regio-isomeric dibenzoxazepinones is reported from 8-aminoquinoline benzamides and 2-bromophenols. Through choice of conditions, the reaction proceeds either through a sequential C–H etherification and subsequent Goldberg reaction, both controlled by the aminoquinoline group and Cu(I), or via a C–H etherification and subsequent Smiles rearrangement promoted by Cu(II) and t-BuOK. The 8-aminoquinoline moiety, e.g., 8-amino-5-methoxyquinoline, is readily removable from the structures of dibenzoxazepinones under moderate conditions.

The enantiomeric purity and absolute configuration of flavanones were first determined using (S)-3,3′-dibromo-1,1′-bi-2-naphthol as a chiral solvating agent by means of 1H NMR spectroscopy. The enantiomeric purity results closely matched those based on chiral HPLC analysis.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are accepted as a favorable class of agents for the treatment of type 2 diabetes. Herein, a series of fused β-homophenylalanine derivatives as novel DPP-4 inhibitors were designed, synthesized, and evaluated for their inhibitory activities against DPP-4. Most of them displayed excellent DPP-4 inhibitory activities and good selectivity. Among them, 9aa, 18a, and 18m also showed good efficacy in an oral glucose tolerance test (OGTT) in ICR mice. Moreover, when dosed 8 h prior to glucose challenge, 18m showed significantly greater potency than sitagliptin. It thus provides potential candidates for the further development into potent drugs targeting DPP-4.Keywords: Diabetes; DPP-4 inhibitor; sitagliptin; β-homophenylalanine derivatives

•Several N-substituted isoquinolones were obtained via [2,3] or [3,3] rearrangement.•4h and 4j showed strong antitumor activities close to vemurafenib and sorafenib.•The unusual [2,3] rearrangement is a novel rearrangement observed on lactams.The present study discovers multiple N-substituted 3-arylisoquinolone derivatives as antitumor agents originating from O-substituted 3-arylisoquinolines via [2,3] or [3,3] rearrangement. The current [2,3] rearrangement of epoxy or acetal O-substituents converting to diol or alcohol N-substituents can be promoted by silica gel or by diluted hydrochloric acid, which is distinct from previously reported [2,3] rearrangements. Some of the derivatives displayed comparable or even stronger cytotoxicity than sorafenib and vemurafenib on HCT116 colon carcinoma and A375 melanoma cell lines. Therefore, the rearrangement via intramolecular carbon-oxygen bond cleavage and carbon-nitrogen bond formation should be a useful approach for developing novel anticancer drugs derived from isoquinolones.Several N-substituted isoquinolones were obtained via [2,3] or [3,3] rearrangement, among which, 4h and 4j showed strong antitumor activities close to vemurafenib and sorafenib.