NGHIÊN CỨU TỔNG HỢP LISINOPRIL DIHYDRATE TỪ CHẤT TRUNG GIAN CHÌA KHÓA N2-[1(S)-ETHOXYCARBONYL-3-PHENYLPROPYL]-N6-TRIFLUOROACETYL-L-LYSINE

Authors

  • Nguyễn Quốc Vượng
  • Vũ Văn Chiến
  • Nguyễn Thị Thu
  • Nguyễn Thị Huế
  • Nguyễn Tiến Đạt
  • Phạm Văn Cường
  • Châu Văn Minh

DOI:

https://doi.org/10.15625/0866-708X/51/2/9582

Keywords:

lisinopril, lysine-L-proline, N, N-carbonyldiimidazole, coupling reaction, peptide synthesis.

Abstract

Lisinopril dihydrate was synthesized from the key intermediate N2-[1(S)-ethoxycarbonyl-3-phenyl propyl]-N6-trifluoroacetyl-L-Lysin (li5). This intermediate was activated to form cyclic N-anhydride compound li6 by using N,N-carbonyldiimidazole, subsequently, the coupling reaction of li6 with L-proline methyl ester (li3) to give fully protected lisinopril derivative li7 in high yield. The last step is the deprotection of li7 via hydrolysis using aqueous solution 1N NaOH in methanol to obtain lisinopril. The crude lisinopril was recrystalized from solvent system isopropanol/H2O(10/1; v/v ml) afforded lisinopril dihydrate li8. The structure of the obtained compounds have been confirmed by IR, ESI-MS, 1H, 13C-NMR, COSY, HMBC, HSQC spectra, and [a]Dsuitable with literatures; The purity of obtained lisinopril li8 was identified by HPLC method and H2O content was determined by Karl Fischer Titration.

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Published

2017-04-09

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Articles