Efficient synthesis of novel conjugated 1, 3, 4-oxadiazole–peptides12. (21st February 2018)

• Record Type: Journal Article
• Authors: Golmohammadi, Farhad; Balalaie, Saeed; Hamdan, Fatima; Maghari, Shokoofeh
• Is Part Of: New journal of chemistry. Volume 42:Number 6(2018)
• Page Start: 4344
• Page End: 4351
• Publication Date: 2018-02-21
• Subjects: Chemistry -- Periodicals; Chimie -- Périodiques; 540
• DOI: 10.1039/c7nj04720g
• Languages: English
• ISSNs: 1144-0546

Abstract

Abstract : In this study, we developed an efficient approach for the synthesis of 2-amino-1, 3, 4-oxadiazoles that are bioisosteres of the amide functional group. The synthesized oxadiazoles were conjugated to octa- and nonapeptides through the C- or N-terminus as precursors of leuprolide acetate. The synthesized compounds are peptidomimetics of leuprolide acetate. Abstract : We were interested in the design and synthesis of novel bioisosteric analogues of leuprolide acetate containing the oxadiazole moiety at the C- or N-terminal of the peptide. An efficient approach for the synthesis of 2-amino-1, 3, 4-oxadiazoles through the reaction of hydrazide with ammonium thiocyanate and desulfurization reaction of the thiosemicarbazides using different coupling reagents was employed. These compounds are bioisosteres of the amide bond. Furthermore, the coupling of 2-amino-1, 3, 4-oxadiazoles at the C-terminal of leuprolide analogues was carried out, using a coupling reagent in the solution phase. On the other hand, the addition of a 2-amino-1, 3, 4-oxadiazole to the N-terminal of the peptide sequence was carried out through the reaction of the 2-amino-1, 3, 4-oxadiazole with succinic anhydride that led to the formation of a carboxylic acid moiety. Addition of the synthesized oxadiazole containing carboxylic acid to the peptide sequence was performed using a coupling reagent and on the surface of the resin. The synthesized peptides containing the oxadiazole moiety at the C- or N-terminal of the peptide sequence are peptidomimetics of leuprolide acetate. All of the synthesized peptides were purified using preparative HPLC and their structures were confirmed using HR-MS (ESI).