Synthesis of chiral N-(2-(1-oxophthalazin-2(1H)-yl) ethanoyl)-α-amino acid derivatives as antitumor agents

A series of chiral alpha-amino acid derivatives conjugated with 1-oxophthalazine moiety 5a-e were synthesized by coupling of various L-acylated amino acid derivatives with 2-(1-oxophthalazin-2(1H)-yl) acetic acid in the presence of 1-hydroxybenzotriazole (HOBt) and N,N'-dicyclohexylcarbodiimide (DCC) as coupling reagent. Alternatively, compounds 5a-e were prepared by the reaction of the corresponding aizde 4, via the azide-coupling method, with L-acylated amino acid derivatives. The peptide esters 5a-d were converted into their corresponding amides 6a-d by treating with methanolic ammonia. Moreover, 5a was boiled with hydrazine hydrate to afford the corresponding hydrazide 7. Finally, the dipeptides 8a-c were prepared by coupling of 5a with the appropriate L-amino acid methyl ester. The synthesized compounds were tested against Caucasian breast adenocarcinoma MCF7 cell line.