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Z. Naturforsch. 2014, 69b, 351 – 361
doi:10.5560/ZNB.2014-3282
Synthesis and Reactions of New Chiral Linear Carboxamides with an Incorporated Peptide Linkage Using Nalidixic Acid and Amino Acids as Starting Materials
Nagy M. Khalifa1,2, Ahmed M. Naglah1,3, Mohamed A. Al-Omar1, Mohamed H. Abo-Ghalia3, and Abd El-Galil E. Amr1,4
1 Pharmaceutical Chemistry Department, Drug Exploration & Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
2 Department of Therapeutical Chemistry, Pharmaceutical and Drug Industries Division, National Research Centre, Dokki 12622, Cairo, Egypt
3 Peptide Chemistry Department, National Research Center, Cairo, Dokki, Egypt
4 Applied Organic Chemistry Department, National Research Center, Cairo, Dokki, Egypt
Reprint requests to Prof. Dr. Abd El-Galil E. Amr. E-mail: aeamr1963@yahoo.com
Received October 5, 2013 / published online March 17, 2014
A series of chiral linear carboxamide derivatives (215) with an incorporated peptide linkage have been prepared via the coupling of 1-ethyl-1,4-dihydro-7-methyl-4-oxo-quinoline-3-carboxylic acid (nalidixic acid, 1) with appropriate amino acid methyl esters. Coupling of 1 with amino acid methyl esters gave the corresponding peptide methyl esters 2, which were hydrolyzed with methanolic sodium hydroxide to the corresponding acids 3. Hydrazinolysis of esters 2 with hydrazine hydrate afforded the corresponding acid hydrazide derivatives 4. The latter compounds were coupled with appropriate aldehydes or acetophenone derivatives to afford the corresponding Schiff base derivatives 5 and 6, respectively. The hydrazide derivative 4b was reacted with phenyl isothiocyanate or carbonyl derivatives to give the corresponding thiosemicarbazide 7 and compounds 810, respectively. Also, 4b was treated with acid monoanhydrides to give the corresponding imide derivatives 1113. Finally, 4b was reacted with tetracarboxylic acid dianhydride derivatives to afford the corresponding diimido carboxamide derivatives 14 and 15.
Key words: 1-Ethyl-1,4-dihydro-7-methyl-4-oxoquinoline-3-carboxylic Acid, Amino Acids, Chiral Derivatives, Schiff Base, Imides
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