Tổng hợp acid (2S)-2-[(3S, 8aR)-3-(4-aminobutyl)- 1,4-dioxohexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl]- 4-phenylbutanoic(R,S,S-diketopiperazin) (tạp D) của lisinopril

In this study, R,S,S-diketopiperazine ((2S)-2-[(3S,8aR)-3-(4-aminobutyl)-1,4-dioxohexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl]-4-phenylbutanoic acid, lisinopril related compound D) were successfully synthesized by ring closure of lisinopril in acetic acid with the yield 67.3%. The structure was determined by UV, IR, MS, NMR (¹H-NMR,
¹³C-NMR, HMBC, HSQC, ROESY, NOESY and COSY). By using HPLC-PDA, its chromatographic purity was determined over 98% on the basis, confirming fully to establish reference substance for lisinopril impurities testing. Moreover, a HPLC method for purity determination of lisinopril related compound D was developed and validated according to ICH guidelines. The method showed selectivity, wide linearity range, and high precision.

Keywords: R,S,S-diketopiperazine, (2S)-2-[(3S, 8aR)-3-(4-aminobutyl)-1,4-dioxohexahydropyrrolo[1,2-a] pyrazin-2(1H)-yl]-4-phenylbutanoic acid, lisinopril related compound D

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